Pub Date : 2024-10-28DOI: 10.1128/msphere.00756-23
Jennafer A P Hamlin, Natalia A Kozak-Muiznieks, Jeffrey W Mercante, Lavanya Rishishwar, Emily T Norris, Anna B Gaines, Maliha K Ishaq, Jonas M Winchell, Melisa J Willby
Legionella pneumophila serogroup 1 sequence types (ST) 213 and 222, a single-locus variant of ST213, were first detected in the early 1990s in the Midwest United States (U.S.) and the late 1990s in the Northeast U.S. and Canada. Since 1992, these STs have increasingly been implicated in community-acquired sporadic and outbreak-associated Legionnaires' disease (LD) cases. We were interested in understanding the change in LD frequency due to these STs and identifying genetic features that differentiate these STs from one another. For the geographic area examined here (Mountain West to Northeast) and over the study period (1992-2020), ST213/222-associated LD cases identified by the Centers for Disease Control and Prevention increased by 0.15 cases per year, with ST213/222-associated LD cases concentrated in four states: Michigan (26%), New York (18%), Minnesota (16%), and Ohio (10%). Additionally, between 2002 and 2021, ST222 caused at least five LD outbreaks in the U.S.; no known outbreaks due to ST213 occurred in the U.S. during this time. We compared the genomes of 230 ST213/222 isolates and found that the mean of the average nucleotide identity (ANI) within each ST was high (99.92% for ST222 and 99.92% for ST213), with a minimum between ST ANI of 99.50% and a maximum of 99.87%, indicating low genetic diversity within and between these STs. While genomic features were identified (e.g., plasmids and CRISPR-Cas systems), no association explained the increasing geographic distribution and prevalence of ST213 and ST222. Yet, we provide evidence of the expanded geographical distribution of ST213 and ST222 in the U.S.IMPORTANCESince the 1990s, cases of Legionnaires' disease (LD) attributed to a pair of closely related Legionella pneumophila variants, ST213 and ST222, have increased in the U.S. Furthermore, between 2002 and 2021, ST222 caused at least five outbreaks of LD in the U.S., while ST213 has not been linked to any U.S. outbreak. We wanted to understand how the rate of LD cases attributed to these variants has changed over time and compare the genetic features of the two variants. Between 1992 and 2020, we determined an increase of 0.15 LD cases ascribed to ST213/222 per year in the geographic region studied. Our research shows that these STs are spreading within the U.S., yet most of the cases occurred in four states: Michigan, New York, Minnesota, and Ohio. Additionally, we found little genetic diversity within and between these STs nor could specific genetic features explain their geographic spread.
{"title":"Expanded geographic distribution for two <i>Legionella pneumophila</i> sequence types of clinical concern.","authors":"Jennafer A P Hamlin, Natalia A Kozak-Muiznieks, Jeffrey W Mercante, Lavanya Rishishwar, Emily T Norris, Anna B Gaines, Maliha K Ishaq, Jonas M Winchell, Melisa J Willby","doi":"10.1128/msphere.00756-23","DOIUrl":"https://doi.org/10.1128/msphere.00756-23","url":null,"abstract":"<p><p><i>Legionella pneumophila</i> serogroup 1 sequence types (ST) 213 and 222, a single-locus variant of ST213, were first detected in the early 1990s in the Midwest United States (U.S.) and the late 1990s in the Northeast U.S. and Canada. Since 1992, these STs have increasingly been implicated in community-acquired sporadic and outbreak-associated Legionnaires' disease (LD) cases. We were interested in understanding the change in LD frequency due to these STs and identifying genetic features that differentiate these STs from one another. For the geographic area examined here (Mountain West to Northeast) and over the study period (1992-2020), ST213/222-associated LD cases identified by the Centers for Disease Control and Prevention increased by 0.15 cases per year, with ST213/222-associated LD cases concentrated in four states: Michigan (26%), New York (18%), Minnesota (16%), and Ohio (10%). Additionally, between 2002 and 2021, ST222 caused at least five LD outbreaks in the U.S.; no known outbreaks due to ST213 occurred in the U.S. during this time. We compared the genomes of 230 ST213/222 isolates and found that the mean of the average nucleotide identity (ANI) within each ST was high (99.92% for ST222 and 99.92% for ST213), with a minimum between ST ANI of 99.50% and a maximum of 99.87%, indicating low genetic diversity within and between these STs. While genomic features were identified (e.g., plasmids and CRISPR-Cas systems), no association explained the increasing geographic distribution and prevalence of ST213 and ST222. Yet, we provide evidence of the expanded geographical distribution of ST213 and ST222 in the U.S.IMPORTANCESince the 1990s, cases of Legionnaires' disease (LD) attributed to a pair of closely related <i>Legionella pneumophila</i> variants, ST213 and ST222, have increased in the U.S. Furthermore, between 2002 and 2021, ST222 caused at least five outbreaks of LD in the U.S., while ST213 has not been linked to any U.S. outbreak. We wanted to understand how the rate of LD cases attributed to these variants has changed over time and compare the genetic features of the two variants. Between 1992 and 2020, we determined an increase of 0.15 LD cases ascribed to ST213/222 per year in the geographic region studied. Our research shows that these STs are spreading within the U.S., yet most of the cases occurred in four states: Michigan, New York, Minnesota, and Ohio. Additionally, we found little genetic diversity within and between these STs nor could specific genetic features explain their geographic spread.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1128/msphere.00847-24
Michael J Imperiale
{"title":"Structured reviews pilot in <i>mSphere</i>.","authors":"Michael J Imperiale","doi":"10.1128/msphere.00847-24","DOIUrl":"10.1128/msphere.00847-24","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1128/msphere.00495-24
Jean-Pierre Musabyimana, Sherihan Musa, Janice Manti, Ute Distler, Stefan Tenzer, Che Julius Ngwa, Gabriele Pradel
<p><p>The lifecycle progression of the malaria parasite <i>Plasmodium falciparum</i> requires precise tuning of gene expression including histone methylation. The histone methyltransferase <i>Pf</i>SET10 was previously described as an H3K4 methyltransferase involved in <i>var</i> gene regulation, making it a prominent antimalarial target. In this study, we investigated the role of <i>Pf</i>SET10 in the blood stages of <i>P. falciparum</i> in more detail, using tagged <i>Pf</i>SET10-knockout (KO) and -knockdown (KD) lines. We demonstrate a nuclear localization of <i>Pf</i>SET10 with peak protein levels in schizonts. <i>Pf</i>SET10 deficiency reduces intraerythrocytic growth but has no effect on gametocyte commitment and maturation. Screening of the <i>Pf</i>SET10-KO line for histone methylation variations reveals that lack of <i>Pf</i>SET10 renders the parasites unable to mark H3K18me1, while no reduction in the H3K4 methylation status could be observed. Comparative transcriptomic profiling of <i>Pf</i>SET10-KO schizonts shows an upregulation of transcripts particularly encoding proteins linked to red blood cell remodeling and antigenic variation, suggesting a repressive function of the histone methylation mark. TurboID coupled with mass spectrometry further highlights an extensive nuclear <i>Pf</i>SET10 interaction network with roles in transcriptional regulation and mRNA processing, DNA replication and repair, and chromatin remodeling. The main interactors of <i>Pf</i>SET10 include ApiAP2 transcription factors, epigenetic regulators like <i>Pf</i>HDAC1, chromatin modulators like <i>Pf</i>MORC and <i>Pf</i>ISWI, mediators of RNA polymerase II, and DNA replication licensing factors. The combined data pinpoint <i>Pf</i>SET10 as a histone methyltransferase essential for H3K18 methylation that regulates nucleic acid metabolic processes in the <i>P. falciparum</i> blood stages as part of a comprehensive chromatin modulation network.IMPORTANCEThe fine-tuned regulation of DNA replication and transcription is particularly crucial for the rapidly multiplying blood stages of malaria parasites and proteins involved in these processes represent important drug targets. This study demonstrates that contrary to previous reports the histone methyltransferase <i>Pf</i>SET10 of the malaria parasite <i>Plasmodium falciparum</i> promotes the methylation of histone 3 at lysine K18, a histone mark to date not well understood. Deficiency of <i>Pf</i>SET10 due to genetic knockout affects genes involved in intraerythrocytic development. Furthermore, in the nuclei of blood-stage parasites, <i>Pf</i>SET10 interacts with various protein complexes crucial for DNA replication, remodeling, and repair, as well as for transcriptional regulation and mRNA processing. In summary, this study highlights <i>Pf</i>SET10 as a methyltransferase affecting H3K18 methylation with critical functions in chromatin maintenance during the development of <i>P. falciparum</i> in red blood cells.</
{"title":"The <i>Plasmodium falciparum</i> histone methyltransferase SET10 participates in a chromatin modulation network crucial for intraerythrocytic development.","authors":"Jean-Pierre Musabyimana, Sherihan Musa, Janice Manti, Ute Distler, Stefan Tenzer, Che Julius Ngwa, Gabriele Pradel","doi":"10.1128/msphere.00495-24","DOIUrl":"https://doi.org/10.1128/msphere.00495-24","url":null,"abstract":"<p><p>The lifecycle progression of the malaria parasite <i>Plasmodium falciparum</i> requires precise tuning of gene expression including histone methylation. The histone methyltransferase <i>Pf</i>SET10 was previously described as an H3K4 methyltransferase involved in <i>var</i> gene regulation, making it a prominent antimalarial target. In this study, we investigated the role of <i>Pf</i>SET10 in the blood stages of <i>P. falciparum</i> in more detail, using tagged <i>Pf</i>SET10-knockout (KO) and -knockdown (KD) lines. We demonstrate a nuclear localization of <i>Pf</i>SET10 with peak protein levels in schizonts. <i>Pf</i>SET10 deficiency reduces intraerythrocytic growth but has no effect on gametocyte commitment and maturation. Screening of the <i>Pf</i>SET10-KO line for histone methylation variations reveals that lack of <i>Pf</i>SET10 renders the parasites unable to mark H3K18me1, while no reduction in the H3K4 methylation status could be observed. Comparative transcriptomic profiling of <i>Pf</i>SET10-KO schizonts shows an upregulation of transcripts particularly encoding proteins linked to red blood cell remodeling and antigenic variation, suggesting a repressive function of the histone methylation mark. TurboID coupled with mass spectrometry further highlights an extensive nuclear <i>Pf</i>SET10 interaction network with roles in transcriptional regulation and mRNA processing, DNA replication and repair, and chromatin remodeling. The main interactors of <i>Pf</i>SET10 include ApiAP2 transcription factors, epigenetic regulators like <i>Pf</i>HDAC1, chromatin modulators like <i>Pf</i>MORC and <i>Pf</i>ISWI, mediators of RNA polymerase II, and DNA replication licensing factors. The combined data pinpoint <i>Pf</i>SET10 as a histone methyltransferase essential for H3K18 methylation that regulates nucleic acid metabolic processes in the <i>P. falciparum</i> blood stages as part of a comprehensive chromatin modulation network.IMPORTANCEThe fine-tuned regulation of DNA replication and transcription is particularly crucial for the rapidly multiplying blood stages of malaria parasites and proteins involved in these processes represent important drug targets. This study demonstrates that contrary to previous reports the histone methyltransferase <i>Pf</i>SET10 of the malaria parasite <i>Plasmodium falciparum</i> promotes the methylation of histone 3 at lysine K18, a histone mark to date not well understood. Deficiency of <i>Pf</i>SET10 due to genetic knockout affects genes involved in intraerythrocytic development. Furthermore, in the nuclei of blood-stage parasites, <i>Pf</i>SET10 interacts with various protein complexes crucial for DNA replication, remodeling, and repair, as well as for transcriptional regulation and mRNA processing. In summary, this study highlights <i>Pf</i>SET10 as a methyltransferase affecting H3K18 methylation with critical functions in chromatin maintenance during the development of <i>P. falciparum</i> in red blood cells.</","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1128/msphere.00255-24
R S Coombs, A E Overacre-Delgoffe, A Bhattacharjee, T W Hand, J P Boyle
Toxoplasma gondii is capable of being transmitted by nearly all warm-blooded animals, and rodents are a major source of parasite dissemination, yet mechanisms driving its broad host range are poorly understood. Although a phylogenetically close relative of T. gondii, Neospora caninum differs from T. gondii in that it does not infect mice and only infects a small number of ruminant and canine species. We recently showed that T. gondii and N. caninum grow similarly in mice during the first 24 h post-infection, but only N. caninum induces an IFNγ-driven response within hours that controls the infection. The goal of the present study was to understand the cellular basis of this rapid response to N. caninum. To do this, we compared immune cell populations at the site of infection 4 h after T. gondii or N. caninum infection in mice. We found that both parasites induced similar frequencies of peritoneal monocytes, while macrophages and dendritic cell populations were not increased compared to uninfected mice. Through a series of knockout mouse experiments, we show that B, T, and NKT cells are not required for immediate IFNγ production and ultimate control of N. caninum infection, suggesting that natural killer (NK) cells are the primary inducers of immediate IFNγ in response to N. caninum. N. caninum infections exhibited significantly more IFNγ+ NK cells in the peritoneum compared with T. gondii-infected and uninfected mice. Finally, we demonstrate that differences in early IFNγ production during N. caninum and T. gondii infections in mice are at least partly due to differences in soluble antigen(s) produced by tachyzoites.
Importance: Pathogen differences in host range are poorly understood at the molecular level even though even closely related pathogen species can have dramatically distinct host ranges. Here, we study two related parasite species that have a dramatic difference in their ability to infect mice. Here, we show that soluble proteins from these species determine one driver of this difference: induction of interferon gamma by cells of the innate immune system.
弓形虫几乎可以通过所有温血动物传播,而啮齿类动物是寄生虫传播的主要来源,但人们对其广泛宿主范围的机制却知之甚少。尽管在系统发育上与淋病双孢子虫是近亲,但犬新孢子虫与淋病双孢子虫不同,它不感染小鼠,只感染少数反刍动物和犬科动物。我们最近的研究表明,在感染后的头 24 小时内,淋病双孢子虫和犬新孢子虫在小鼠体内的生长情况相似,但只有犬新孢子虫能在数小时内诱导 IFNγ 驱动的反应,从而控制感染。本研究的目的是了解这种对 N. caninum 快速反应的细胞基础。为此,我们比较了小鼠感染 T. gondii 或 N. caninum 4 小时后感染部位的免疫细胞群。我们发现这两种寄生虫诱导的腹膜单核细胞的频率相似,而巨噬细胞和树突状细胞的数量与未感染的小鼠相比并没有增加。通过一系列基因敲除小鼠实验,我们发现B、T和NKT细胞不是产生即时IFNγ和最终控制犬疫母细胞感染所必需的,这表明自然杀伤(NK)细胞是应对犬疫母细胞感染的即时IFNγ的主要诱导因子。与淋球菌感染小鼠和未感染小鼠相比,N. caninum 感染小鼠腹膜中的 IFNγ+ NK 细胞明显增多。最后,我们证明了小鼠感染 N. caninum 和 T. gondii 期间早期 IFNγ 产生的差异至少部分是由于速生虫产生的可溶性抗原的差异:病原体在宿主范围上的差异在分子水平上还鲜为人知,即使是密切相关的病原体物种也可能具有截然不同的宿主范围。在这里,我们研究了两种相关的寄生虫,它们感染小鼠的能力存在巨大差异。在这里,我们发现这两种寄生虫的可溶性蛋白决定了这种差异的一个驱动因素:先天性免疫系统细胞诱导γ干扰素。
{"title":"Mouse innate resistance to <i>Neospora caninum</i> infection is driven by early production of IFNγ by NK cells in response to parasite ligands.","authors":"R S Coombs, A E Overacre-Delgoffe, A Bhattacharjee, T W Hand, J P Boyle","doi":"10.1128/msphere.00255-24","DOIUrl":"10.1128/msphere.00255-24","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i> is capable of being transmitted by nearly all warm-blooded animals, and rodents are a major source of parasite dissemination, yet mechanisms driving its broad host range are poorly understood. Although a phylogenetically close relative of <i>T. gondii</i>, <i>Neospora caninum</i> differs from <i>T. gondii</i> in that it does not infect mice and only infects a small number of ruminant and canine species. We recently showed that <i>T. gondii</i> and <i>N. caninum</i> grow similarly in mice during the first 24 h post-infection, but only <i>N. caninum</i> induces an IFNγ-driven response within hours that controls the infection. The goal of the present study was to understand the cellular basis of this rapid response to <i>N. caninum</i>. To do this, we compared immune cell populations at the site of infection 4 h after <i>T. gondii</i> or <i>N. caninum</i> infection in mice. We found that both parasites induced similar frequencies of peritoneal monocytes, while macrophages and dendritic cell populations were not increased compared to uninfected mice. Through a series of knockout mouse experiments, we show that B, T, and NKT cells are not required for immediate IFNγ production and ultimate control of <i>N. caninum</i> infection, suggesting that natural killer (NK) cells are the primary inducers of immediate IFNγ in response to <i>N. caninum. N. caninum</i> infections exhibited significantly more IFNγ<sup>+</sup> NK cells in the peritoneum compared with <i>T. gondii</i>-infected and uninfected mice. Finally, we demonstrate that differences in early IFNγ production during <i>N. caninum</i> and <i>T. gondii</i> infections in mice are at least partly due to differences in soluble antigen(s) produced by tachyzoites.</p><p><strong>Importance: </strong>Pathogen differences in host range are poorly understood at the molecular level even though even closely related pathogen species can have dramatically distinct host ranges. Here, we study two related parasite species that have a dramatic difference in their ability to infect mice. Here, we show that soluble proteins from these species determine one driver of this difference: induction of interferon gamma by cells of the innate immune system.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1128/msphere.00546-24
Matthias Wyss, Abhishek Kanyal, Igor Niederwieser, Richard Bartfai, Till S Voss
<p><p>The malaria parasite <i>Plasmodium falciparum</i> employs antigenic variation of the virulence factor <i>P. falciparum</i> erythrocyte membrane protein 1 (PfEMP1) to escape adaptive immune responses during blood infection. Antigenic variation of PfEMP1 occurs through epigenetic switches in the mutually exclusive expression of individual members of the multi-copy <i>var</i> gene family. <i>var</i> genes are located in perinuclear clusters of transcriptionally inactive heterochromatin. Singular <i>var</i> gene activation is linked to locus repositioning into a dedicated zone at the nuclear periphery and deposition of histone 3 lysine 4 di-/trimethylation (H3K4me2/3) and H3K9 acetylation marks in the promoter region. While previous work identified the putative H3K4-specific methyltransferase PfSET10 as an essential enzyme and positive regulator of <i>var</i> gene expression, a recent study reported conflicting data. Here, we used iterative genome editing to engineer a conditional PfSET10 knockout line tailored to study the function of PfSET10 in <i>var</i> gene regulation. We demonstrate that PfSET10 is not required for mutually exclusive <i>var</i> gene expression and switching. We also show that PfSET10 is dispensable not only for asexual parasite proliferation but also for sexual conversion and gametocyte differentiation. Furthermore, comparative RNA-seq experiments revealed that PfSET10 plays no obvious role in regulating gene expression during asexual parasite development and gametocytogenesis. Interestingly, however, PfSET10 shows different subnuclear localization patterns in asexual and sexual stage parasites and female-specific expression in mature gametocytes. In summary, our work confirms in detail that PfSET10 is not involved in regulating <i>var</i> gene expression and is not required for blood-stage parasite viability, indicating PfSET10 may be important for life cycle progression in the mosquito vector or during liver stage development.IMPORTANCEThe malaria parasite <i>Plasmodium falciparum</i> infects hundreds of millions of people every year. To survive and proliferate in the human bloodstream, the parasites need to escape recognition by the host's immune system. To achieve this, <i>P. falciparum</i> can change the expression of surface antigens <i>via</i> a process called antigenic variation. This fascinating survival strategy is based on infrequent switches in the expression of single members of the <i>var</i> multigene family. Previous research reported conflicting results on the role of the epigenetic regulator PfSET10 in controlling mutually exclusive <i>var</i> gene expression and switching. Here, we unequivocally demonstrate that PfSET10 is neither required for antigenic variation nor the expression of any other proteins during blood-stage infection. This information is critical in directing our attention toward exploring alternative molecular mechanisms underlying the control of antigenic variation and investigating the
{"title":"The <i>Plasmodium falciparum</i> histone methyltransferase PfSET10 is dispensable for the regulation of antigenic variation and gene expression in blood-stage parasites.","authors":"Matthias Wyss, Abhishek Kanyal, Igor Niederwieser, Richard Bartfai, Till S Voss","doi":"10.1128/msphere.00546-24","DOIUrl":"https://doi.org/10.1128/msphere.00546-24","url":null,"abstract":"<p><p>The malaria parasite <i>Plasmodium falciparum</i> employs antigenic variation of the virulence factor <i>P. falciparum</i> erythrocyte membrane protein 1 (PfEMP1) to escape adaptive immune responses during blood infection. Antigenic variation of PfEMP1 occurs through epigenetic switches in the mutually exclusive expression of individual members of the multi-copy <i>var</i> gene family. <i>var</i> genes are located in perinuclear clusters of transcriptionally inactive heterochromatin. Singular <i>var</i> gene activation is linked to locus repositioning into a dedicated zone at the nuclear periphery and deposition of histone 3 lysine 4 di-/trimethylation (H3K4me2/3) and H3K9 acetylation marks in the promoter region. While previous work identified the putative H3K4-specific methyltransferase PfSET10 as an essential enzyme and positive regulator of <i>var</i> gene expression, a recent study reported conflicting data. Here, we used iterative genome editing to engineer a conditional PfSET10 knockout line tailored to study the function of PfSET10 in <i>var</i> gene regulation. We demonstrate that PfSET10 is not required for mutually exclusive <i>var</i> gene expression and switching. We also show that PfSET10 is dispensable not only for asexual parasite proliferation but also for sexual conversion and gametocyte differentiation. Furthermore, comparative RNA-seq experiments revealed that PfSET10 plays no obvious role in regulating gene expression during asexual parasite development and gametocytogenesis. Interestingly, however, PfSET10 shows different subnuclear localization patterns in asexual and sexual stage parasites and female-specific expression in mature gametocytes. In summary, our work confirms in detail that PfSET10 is not involved in regulating <i>var</i> gene expression and is not required for blood-stage parasite viability, indicating PfSET10 may be important for life cycle progression in the mosquito vector or during liver stage development.IMPORTANCEThe malaria parasite <i>Plasmodium falciparum</i> infects hundreds of millions of people every year. To survive and proliferate in the human bloodstream, the parasites need to escape recognition by the host's immune system. To achieve this, <i>P. falciparum</i> can change the expression of surface antigens <i>via</i> a process called antigenic variation. This fascinating survival strategy is based on infrequent switches in the expression of single members of the <i>var</i> multigene family. Previous research reported conflicting results on the role of the epigenetic regulator PfSET10 in controlling mutually exclusive <i>var</i> gene expression and switching. Here, we unequivocally demonstrate that PfSET10 is neither required for antigenic variation nor the expression of any other proteins during blood-stage infection. This information is critical in directing our attention toward exploring alternative molecular mechanisms underlying the control of antigenic variation and investigating the","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1128/msphere.00524-24
Debasmita Saha, Justin B Gregor, Smriti Hoda, Katharine E Eastman, Victor A Gutierrez-Schultz, Mindy Navarrete, Jennifer H Wisecaver, Scott D Briggs
Candida glabrata exhibits innate resistance to azole antifungal drugs but also has the propensity to rapidly develop clinical drug resistance. Azole drugs, which target Erg11, is one of the major classes of antifungals used to treat Candida infections. Despite their widespread use, the mechanism controlling azole-induced ERG gene expression and drug resistance in C. glabrata has primarily revolved around Upc2 and/or Pdr1. Phylogenetic and syntenic analyses revealed that C. glabrata, following a whole genome duplication event, maintained HAP1A and HAP1B, whereas Saccharomyces cerevisiae only retained the HAP1A ortholog, HAP1. In this study, we determined the function of two zinc cluster transcription factors, Hap1A and Hap1B, as direct regulators of ERG genes. In S. cerevisiae, Hap1, an ortholog of Hap1A, is a known transcription factor controlling ERG gene expression under aerobic and hypoxic conditions. Interestingly, deleting HAP1 or HAP1B in either S. cerevisiae or C. glabrata, respectively, showed altered susceptibility to azoles. In contrast, the strain deleted for HAP1A did not exhibit azole susceptibility. We also determined that the increased azole susceptibility in a hap1BΔ strain is attributed to decreased azole-induced expression of ERG genes, resulting in decreased levels of total ergosterol. Surprisingly, Hap1A protein expression is barely detected under aerobic conditions but is specifically induced under hypoxic conditions, where Hap1A is required for the repression of ERG genes. However, in the absence of Hap1A, Hap1B can compensate as a transcriptional repressor. Our study shows that Hap1A and Hap1B is utilized by C. glabrata to adapt to specific host and environmental conditions.
Importance: Invasive and drug-resistant fungal infections pose a significant public health concern. Candida glabrata, a human fungal pathogen, is often difficult to treat due to its intrinsic resistance to azole antifungal drugs and its capacity to develop clinical drug resistance. Therefore, understanding the pathways that facilitate fungal growth and environmental adaptation may lead to novel drug targets and/or more efficacious antifungal therapies. While the mechanisms of azole resistance in Candida species have been extensively studied, the roles of zinc cluster transcription factors, such as Hap1A and Hap1B, in C. glabrata have remained largely unexplored until now. Our research shows that these factors play distinct yet crucial roles in regulating ergosterol homeostasis under azole drug treatment and oxygen-limiting growth conditions. These findings offer new insights into how this pathogen adapts to different environmental conditions and enhances our understanding of factors that alter drug susceptibility and/or resistance.
{"title":"<i>Candida glabrata</i> maintains two <i>HAP1</i> ohnologs, <i>HAP1A</i> and <i>HAP1B</i>, for distinct roles in ergosterol gene regulation to mediate sterol homeostasis under azole and hypoxic conditions.","authors":"Debasmita Saha, Justin B Gregor, Smriti Hoda, Katharine E Eastman, Victor A Gutierrez-Schultz, Mindy Navarrete, Jennifer H Wisecaver, Scott D Briggs","doi":"10.1128/msphere.00524-24","DOIUrl":"10.1128/msphere.00524-24","url":null,"abstract":"<p><p><i>Candida glabrata</i> exhibits innate resistance to azole antifungal drugs but also has the propensity to rapidly develop clinical drug resistance. Azole drugs, which target Erg11, is one of the major classes of antifungals used to treat <i>Candida</i> infections. Despite their widespread use, the mechanism controlling azole-induced <i>ERG</i> gene expression and drug resistance in <i>C. glabrata</i> has primarily revolved around Upc2 and/or Pdr1. Phylogenetic and syntenic analyses revealed that <i>C. glabrata</i>, following a whole genome duplication event, maintained <i>HAP1A</i> and <i>HAP1B</i>, whereas <i>Saccharomyces cerevisiae</i> only retained the <i>HAP1A</i> ortholog, <i>HAP1</i>. In this study, we determined the function of two zinc cluster transcription factors, Hap1A and Hap1B, as direct regulators of <i>ERG</i> genes. In <i>S. cerevisiae,</i> Hap1, an ortholog of Hap1A, is a known transcription factor controlling <i>ERG</i> gene expression under aerobic and hypoxic conditions. Interestingly, deleting <i>HAP1</i> or <i>HAP1B</i> in either <i>S. cerevisiae</i> or <i>C. glabrata,</i> respectively, showed altered susceptibility to azoles. In contrast, the strain deleted for <i>HAP1A</i> did not exhibit azole susceptibility. We also determined that the increased azole susceptibility in a <i>hap1B</i>Δ strain is attributed to decreased azole-induced expression of <i>ERG</i> genes, resulting in decreased levels of total ergosterol. Surprisingly, Hap1A protein expression is barely detected under aerobic conditions but is specifically induced under hypoxic conditions, where Hap1A is required for the repression of <i>ERG</i> genes. However, in the absence of Hap1A, Hap1B can compensate as a transcriptional repressor. Our study shows that Hap1A and Hap1B is utilized by <i>C. glabrata</i> to adapt to specific host and environmental conditions.</p><p><strong>Importance: </strong>Invasive and drug-resistant fungal infections pose a significant public health concern. <i>Candida glabrata</i>, a human fungal pathogen, is often difficult to treat due to its intrinsic resistance to azole antifungal drugs and its capacity to develop clinical drug resistance. Therefore, understanding the pathways that facilitate fungal growth and environmental adaptation may lead to novel drug targets and/or more efficacious antifungal therapies. While the mechanisms of azole resistance in <i>Candida</i> species have been extensively studied, the roles of zinc cluster transcription factors, such as Hap1A and Hap1B, in <i>C. glabrata</i> have remained largely unexplored until now. Our research shows that these factors play distinct yet crucial roles in regulating ergosterol homeostasis under azole drug treatment and oxygen-limiting growth conditions. These findings offer new insights into how this pathogen adapts to different environmental conditions and enhances our understanding of factors that alter drug susceptibility and/or resistance.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1128/msphere.00647-24
Parul Kapil, Yihui Wang, Kelsey Gregg, Lindsey Zimmerman, Damaris Molano, Jonatan Maldonado Villeda, Peter Sebo, Tod J Merkel
Whole-cell pertussis (wP) vaccines introduced in the 1940s led to a dramatic reduction of pertussis incidence and are still widely used in low- and middle-income countries (LMICs) worldwide. The reactogenicity of wP vaccines resulted in reduced public acceptance, which drove the development and introduction of acellular pertussis (aP) vaccines in high-income countries in the 1990s. Increased incidence of pertussis disease has been observed in high-income countries following the introduction of aP vaccines despite near universal rates of pediatric vaccination. These increases are attributed to the reduced protection against colonization, carriage, and transmission as well as reduced duration of immunity conferred by aP vaccines relative to the wP vaccines they replaced. A reduced reactogenicity whole-cell pertussis (RRwP) vaccine was recently developed with the goal of achieving the same protection as conferred by wP vaccination but with an improved safety profile, which may benefit countries in which wP vaccines are still in routine use. In this study, we tested the RRwP vaccine in a baboon model of pertussis infection. We found that the RRwP vaccine induced comparable cellular and humoral immune responses and comparable protection following challenge relative to the wP vaccine, while significantly reducing injection-site reactogenicity.IMPORTANCEThe World Health Organization (WHO) recommended in 2015 that countries administering wP vaccines in their national vaccine programs should continue to do so, and that switching to aP vaccines for primary infant immunization should only be considered if periodic booster vaccinations and/or maternal immunization could be assured and sustained in their national immunization schedules (WHO, Vaccine 34:1423-1425, 2016, https://doi.org/10.1016/j.vaccine.2015.10.136). Due to the considerably higher cost of aP vaccines and the larger number of doses required, most LMICs continue to use wP vaccines. The development and introduction of a wP vaccine that induces fewer adverse events without sacrificing protection would significantly benefit countries in which wP vaccines are still in routine use. The results of this study indicate this desirable goal may be achievable.
20 世纪 40 年代引入的全细胞百日咳(wP)疫苗使百日咳发病率大幅下降,目前仍在全球中低收入国家广泛使用。wP 疫苗的致反应性降低了公众的接受度,这推动了 20 世纪 90 年代无细胞百日咳 (aP) 疫苗在高收入国家的开发和引入。尽管儿科疫苗接种率接近普及,但在引入 aP 疫苗后,高收入国家的百日咳发病率仍有所上升。发病率上升的原因是 aP 疫苗对定植、携带和传播的保护能力降低,而且相对于被其取代的 wP 疫苗,aP 疫苗的免疫持续时间缩短。最近开发出了一种致病反应性降低的全细胞百日咳疫苗(RRwP),其目标是实现与 wP 疫苗相同的保护效果,但安全性有所提高,这可能会使仍在常规使用 wP 疫苗的国家受益。在这项研究中,我们在百日咳狒狒感染模型中测试了 RRwP 疫苗。我们发现,与 wP 疫苗相比,RRwP 疫苗可诱导相似的细胞和体液免疫反应,并在挑战后产生相似的保护作用,同时显著降低了注射部位的致反应性。重要意义世界卫生组织(WHO)于2015年建议,在国家疫苗计划中接种wP疫苗的国家应继续接种wP疫苗,只有在国家免疫计划中能确保和维持定期加强免疫和/或母体免疫接种的情况下,才应考虑改用aP疫苗进行婴儿初次免疫接种(WHO,Vaccine 34:1423-1425,2016,https://doi.org/10.1016/j.vaccine.2015.10.136).由于 aP 疫苗的成本远高于 aP 疫苗,且所需剂量较大,大多数低收入国家仍在使用 wP 疫苗。开发和引入一种可在不牺牲保护作用的前提下减少不良反应的 wP 疫苗将使仍在常规使用 wP 疫苗的国家受益匪浅。本研究的结果表明这一理想目标是可以实现的。
{"title":"A whole-cell pertussis vaccine engineered to elicit reduced reactogenicity protects baboons against pertussis challenge.","authors":"Parul Kapil, Yihui Wang, Kelsey Gregg, Lindsey Zimmerman, Damaris Molano, Jonatan Maldonado Villeda, Peter Sebo, Tod J Merkel","doi":"10.1128/msphere.00647-24","DOIUrl":"https://doi.org/10.1128/msphere.00647-24","url":null,"abstract":"<p><p>Whole-cell pertussis (wP) vaccines introduced in the 1940s led to a dramatic reduction of pertussis incidence and are still widely used in low- and middle-income countries (LMICs) worldwide. The reactogenicity of wP vaccines resulted in reduced public acceptance, which drove the development and introduction of acellular pertussis (aP) vaccines in high-income countries in the 1990s. Increased incidence of pertussis disease has been observed in high-income countries following the introduction of aP vaccines despite near universal rates of pediatric vaccination. These increases are attributed to the reduced protection against colonization, carriage, and transmission as well as reduced duration of immunity conferred by aP vaccines relative to the wP vaccines they replaced. A reduced reactogenicity whole-cell pertussis (RRwP) vaccine was recently developed with the goal of achieving the same protection as conferred by wP vaccination but with an improved safety profile, which may benefit countries in which wP vaccines are still in routine use. In this study, we tested the RRwP vaccine in a baboon model of pertussis infection. We found that the RRwP vaccine induced comparable cellular and humoral immune responses and comparable protection following challenge relative to the wP vaccine, while significantly reducing injection-site reactogenicity.IMPORTANCEThe World Health Organization (WHO) recommended in 2015 that countries administering wP vaccines in their national vaccine programs should continue to do so, and that switching to aP vaccines for primary infant immunization should only be considered if periodic booster vaccinations and/or maternal immunization could be assured and sustained in their national immunization schedules (WHO, Vaccine 34:1423-1425, 2016, https://doi.org/10.1016/j.vaccine.2015.10.136). Due to the considerably higher cost of aP vaccines and the larger number of doses required, most LMICs continue to use wP vaccines. The development and introduction of a wP vaccine that induces fewer adverse events without sacrificing protection would significantly benefit countries in which wP vaccines are still in routine use. The results of this study indicate this desirable goal may be achievable.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1128/msphere.00560-24
Rebecca L Bacon, Carolyn L Hodo, Jing Wu, Shannara Welch, Colette Nickodem, Javier Vinasco, Deborah Threadgill, Stanton B Gray, Keri N Norman, Sara D Lawhon
<p><p><i>Campylobacter jejuni</i> and <i>Campylobacter coli</i> represent the leading causes of bacterial gastroenteritis in humans, and infections can produce post-infectious irritable bowel syndrome (PI-IBS). Rhesus macaques (<i>Macaca mulatta</i>) (RM) are similarly susceptible to acute campylobacteriosis and represent a potential model of PI-IBS. We characterized the <i>Campylobacter</i> species circulating in an RM breeding colony using culture, qPCR, and whole genome sequencing (WGS). We also compared the <i>C. jejuni</i> and <i>C. coli</i> prevalence in RM as detected with qPCR versus culture and identified risk factors for bacteria presence and intestinal disease. Culture of 275 samples yielded <i>C. coli</i> (103) and <i>C. jejuni</i> (8), of which 21.6% were resistant to quinolones and 3.6% were resistant to macrolides. Multidrug-resistant isolates were obtained exclusively from animals exhibiting diarrhea or with histologically confirmed chronic enterocolitis. WGS revealed a non-clonal population of <i>Campylobacter</i> spp. Genotypic predictions of resistance were excellent except for aminoglycosides. All sequenced isolates contained genes for all subunits of cytolethal distending toxin. qPCR detected a prevalence of 45.9% for <i>C. coli</i> and 29.6% for <i>C. jejuni</i>. The quantity of either bacteria was significantly higher (<i>P</i> < 0.05) in animals with intestinal disease compared to healthy animals, though only young age was significantly associated with the presence of <i>Campylobacter</i> sp. or intestinal disease. Significantly more <i>C. jejuni</i> positive animals were detected with qPCR than with culture. These results provide a comprehensive characterization of <i>Campylobacter</i> spp. circulating in a breeding colony of RM in the United States and suggest that qPCR is superior for the detection of <i>C. jejuni</i> in RM.</p><p><strong>Importance: </strong>Gastrointestinal disease is one of the most common reasons for hospitalization in non-human primate colonies and accounts for over one-third of non-research related euthanasia. In rhesus macaques, this manifests as both acute diarrhea and chronic enterocolitis (CE), a syndrome of chronic diarrhea resulting in poor weight gain or weight loss which is minimally responsive to treatment. <i>Campylobacter</i> spp. are major causes of acute enterocolitis in rhesus macaques and may predispose individuals to the development of CE, similar to post-infectious irritable bowel syndrome in humans. Despite these concerns, there are few studies characterizing <i>Campylobacter</i> in rhesus macaque colonies, in particular utilizing whole genome sequencing and assessing findings with respect to the health status of the host. Our findings provide insight into <i>Campylobacter</i> strains circulating in rhesus macaque colonies, which can improve clinical monitoring, assist in treatment decisions, and provide new avenues of investigation into campylobacteriosis as a catalyst for CE.</
{"title":"Diversity of <i>Campylobacter</i> spp. circulating in a rhesus macaque (<i>Macaca mulatta</i>) breeding colony using culture and molecular methods.","authors":"Rebecca L Bacon, Carolyn L Hodo, Jing Wu, Shannara Welch, Colette Nickodem, Javier Vinasco, Deborah Threadgill, Stanton B Gray, Keri N Norman, Sara D Lawhon","doi":"10.1128/msphere.00560-24","DOIUrl":"10.1128/msphere.00560-24","url":null,"abstract":"<p><p><i>Campylobacter jejuni</i> and <i>Campylobacter coli</i> represent the leading causes of bacterial gastroenteritis in humans, and infections can produce post-infectious irritable bowel syndrome (PI-IBS). Rhesus macaques (<i>Macaca mulatta</i>) (RM) are similarly susceptible to acute campylobacteriosis and represent a potential model of PI-IBS. We characterized the <i>Campylobacter</i> species circulating in an RM breeding colony using culture, qPCR, and whole genome sequencing (WGS). We also compared the <i>C. jejuni</i> and <i>C. coli</i> prevalence in RM as detected with qPCR versus culture and identified risk factors for bacteria presence and intestinal disease. Culture of 275 samples yielded <i>C. coli</i> (103) and <i>C. jejuni</i> (8), of which 21.6% were resistant to quinolones and 3.6% were resistant to macrolides. Multidrug-resistant isolates were obtained exclusively from animals exhibiting diarrhea or with histologically confirmed chronic enterocolitis. WGS revealed a non-clonal population of <i>Campylobacter</i> spp. Genotypic predictions of resistance were excellent except for aminoglycosides. All sequenced isolates contained genes for all subunits of cytolethal distending toxin. qPCR detected a prevalence of 45.9% for <i>C. coli</i> and 29.6% for <i>C. jejuni</i>. The quantity of either bacteria was significantly higher (<i>P</i> < 0.05) in animals with intestinal disease compared to healthy animals, though only young age was significantly associated with the presence of <i>Campylobacter</i> sp. or intestinal disease. Significantly more <i>C. jejuni</i> positive animals were detected with qPCR than with culture. These results provide a comprehensive characterization of <i>Campylobacter</i> spp. circulating in a breeding colony of RM in the United States and suggest that qPCR is superior for the detection of <i>C. jejuni</i> in RM.</p><p><strong>Importance: </strong>Gastrointestinal disease is one of the most common reasons for hospitalization in non-human primate colonies and accounts for over one-third of non-research related euthanasia. In rhesus macaques, this manifests as both acute diarrhea and chronic enterocolitis (CE), a syndrome of chronic diarrhea resulting in poor weight gain or weight loss which is minimally responsive to treatment. <i>Campylobacter</i> spp. are major causes of acute enterocolitis in rhesus macaques and may predispose individuals to the development of CE, similar to post-infectious irritable bowel syndrome in humans. Despite these concerns, there are few studies characterizing <i>Campylobacter</i> in rhesus macaque colonies, in particular utilizing whole genome sequencing and assessing findings with respect to the health status of the host. Our findings provide insight into <i>Campylobacter</i> strains circulating in rhesus macaque colonies, which can improve clinical monitoring, assist in treatment decisions, and provide new avenues of investigation into campylobacteriosis as a catalyst for CE.</","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bacillus cereus, a global threat, is one of the major causes of toxin-induced foodborne diseases. However, a comprehensive assessment of the prevalence and characteristics of B. cereus worldwide is still lacking. Here, we applied whole-genome sequence analysis to 191 B. cereus collected in Africa, America, Asia, Europe, and Oceania from the 1900s to 2022, finding that CC142 dominated the global B. cereus clonal complex. The results provided direct evidence that B. cereus could spread through the food chain and intercontinentally. B. cereus from different generations worldwide showed coherence in the antibiotic-resistant gene and virulence and biofilm gene profiles, although with high genomic heterogeneity. The BCI-BCII-vanZF-fosB profiles and virulence and biofilm genes were detected at high rates, and we emphasized that B. cereus would pose a serious challenge to global public health and clinical treatment.IMPORTANCEThis study first emphasized the prevalence, genetic characteristics, and pathogenicity of Bacillus cereus worldwide from the 1900s to 2022 using whole-genome sequence analysis. The CC142 dominated the global Bacillus cereus clonal complex. Moreover, we revealed a close evolutionary relationship between the isolates from different sources. B. cereus isolates from different generations worldwide showed coherence in potential pathogenicity, although with high genomic heterogeneity. The BCI-BCII-vanZF-fosB profiles and virulence and biofilm genes were detected at high rates, and we emphasized that B. cereus would pose a serious challenge to global public health and clinical treatment.
{"title":"First insights into the prevalence, genetic characteristics, and pathogenicity of <i>Bacillus cereus</i> from generations worldwide.","authors":"Cuihong Tong, Danyu Xiao, Qi Li, Jing Gou, Shuang Wang, Zhenling Zeng, Wenguang Xiong","doi":"10.1128/msphere.00702-24","DOIUrl":"https://doi.org/10.1128/msphere.00702-24","url":null,"abstract":"<p><p><i>Bacillus cereus</i>, a global threat, is one of the major causes of toxin-induced foodborne diseases. However, a comprehensive assessment of the prevalence and characteristics of <i>B. cereus</i> worldwide is still lacking. Here, we applied whole-genome sequence analysis to 191 <i>B. cereus</i> collected in Africa, America, Asia, Europe, and Oceania from the 1900s to 2022, finding that CC142 dominated the global <i>B. cereus</i> clonal complex. The results provided direct evidence that <i>B. cereus</i> could spread through the food chain and intercontinentally. <i>B. cereus</i> from different generations worldwide showed coherence in the antibiotic-resistant gene and virulence and biofilm gene profiles, although with high genomic heterogeneity. The <i>BCI-BCII-vanZF-fosB</i> profiles and virulence and biofilm genes were detected at high rates, and we emphasized that <i>B. cereus</i> would pose a serious challenge to global public health and clinical treatment.IMPORTANCEThis study first emphasized the prevalence, genetic characteristics, and pathogenicity of <i>Bacillus cereus</i> worldwide from the 1900s to 2022 using whole-genome sequence analysis. The CC142 dominated the global <i>Bacillus cereus</i> clonal complex. Moreover, we revealed a close evolutionary relationship between the isolates from different sources. <i>B. cereus</i> isolates from different generations worldwide showed coherence in potential pathogenicity, although with high genomic heterogeneity. The <i>BCI-BCII-vanZF-fosB</i> profiles and virulence and biofilm genes were detected at high rates, and we emphasized that <i>B. cereus</i> would pose a serious challenge to global public health and clinical treatment.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1128/msphere.00835-24
Md Kamrul Hasan, Marjorie Pizarro-Guajardo, Javier Sanchez, Revathi Govind
{"title":"Erratum for Hasan et al., \"Role of glycogen metabolism in <i>Clostridioides difficile</i> virulence\".","authors":"Md Kamrul Hasan, Marjorie Pizarro-Guajardo, Javier Sanchez, Revathi Govind","doi":"10.1128/msphere.00835-24","DOIUrl":"10.1128/msphere.00835-24","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}