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Expanded geographic distribution for two Legionella pneumophila sequence types of clinical concern. 扩大两种临床关注的嗜肺军团菌序列类型的地理分布。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-28 DOI: 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.

嗜肺军团菌第 1 血清群序列类型(ST)213 和 222(ST213 的单病灶变异型)分别于 20 世纪 90 年代初和 20 世纪 90 年代末首次在美国中西部和美国东北部及加拿大发现。自 1992 年以来,这些 STs 越来越多地与社区获得性散发性和爆发性军团病(LD)病例有关。我们有兴趣了解这些 ST 导致的退伍军人病症频率的变化,并找出区分这些 ST 的遗传特征。在本文研究的地理区域(西部山区到东北部)和研究期间(1992-2020 年),美国疾病控制和预防中心确定的 ST213/222 相关 LD 病例每年增加 0.15 例,ST213/222 相关 LD 病例主要集中在四个州:密歇根州(26%)、纽约州(18%)、明尼苏达州(16%)和俄亥俄州(10%)。此外,在 2002 年至 2021 年期间,ST222 在美国至少引起了五次 LD 病例暴发;在此期间,美国没有发生过已知的 ST213 导致的病例暴发。我们比较了 230 个 ST213/222 分离物的基因组,发现每个 ST 内部的平均核苷酸同一性(ANI)很高(ST222 为 99.92%,ST213 为 99.92%),ST 之间的 ANI 最低为 99.50%,最高为 99.87%,表明这些 ST 内部和之间的遗传多样性很低。虽然确定了基因组特征(如质粒和 CRISPR-Cas 系统),但没有发现任何关联能解释 ST213 和 ST222 地理分布和流行率不断增加的原因。重要意义自 20 世纪 90 年代以来,由一对密切相关的嗜肺军团菌变种 ST213 和 ST222 引起的军团病(LD)病例在美国有所增加。我们希望了解这些变异体导致的 LD 病例发生率随着时间的推移发生了怎样的变化,并比较这两种变异体的遗传特征。从 1992 年到 2020 年,我们确定在所研究的地理区域内,ST213/222 导致的 LD 病例每年增加 0.15 例。我们的研究表明,这些 ST 变体正在美国蔓延,但大多数病例发生在四个州:密歇根州、纽约州、明尼苏达州和俄亥俄州。此外,我们发现这些 STs 内部和之间几乎没有遗传多样性,特定的遗传特征也无法解释其地理分布。
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引用次数: 0
Structured reviews pilot in mSphere. mSphere 中的结构化审查试点。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-28 DOI: 10.1128/msphere.00847-24
Michael J Imperiale
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引用次数: 0
The Plasmodium falciparum histone methyltransferase SET10 participates in a chromatin modulation network crucial for intraerythrocytic development. 恶性疟原虫组蛋白甲基转移酶 SET10 参与了对红细胞内发育至关重要的染色质调节网络。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-24 DOI: 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.</
恶性疟原虫生命周期的进展需要对包括组蛋白甲基化在内的基因表达进行精确调节。组蛋白甲基转移酶 PfSET10 先前被描述为一种参与变异基因调控的 H3K4 甲基转移酶,因此成为一个重要的抗疟靶标。在这项研究中,我们使用标记的 PfSET10 基因敲除(KO)和基因敲除(KD)系,更详细地研究了 PfSET10 在恶性疟原虫血液阶段的作用。我们证明了 PfSET10 的核定位,其蛋白水平在裂殖体中达到峰值。PfSET10 缺乏会降低红细胞内的生长,但对配子细胞的形成和成熟没有影响。对 PfSET10-KO 株系进行组蛋白甲基化变异筛选后发现,缺乏 PfSET10 会使寄生虫无法标记 H3K18me1,而 H3K4 甲基化状态则不会降低。对 PfSET10-KO 裂殖体进行的转录组比较分析表明,编码与红细胞重塑和抗原变异有关的蛋白质的转录本上调,这表明组蛋白甲基化标记具有抑制功能。TurboID 与质谱联用进一步凸显了广泛的核 PfSET10 相互作用网络,该网络在转录调控和 mRNA 处理、DNA 复制和修复以及染色质重塑中发挥作用。PfSET10 的主要相互作用者包括 ApiAP2 转录因子、PfHDAC1 等表观遗传调节因子、PfMORC 和 PfISWI 等染色质调节因子、RNA 聚合酶 II 的介导因子以及 DNA 复制许可因子。综合数据表明,PfSET10 是一种组蛋白甲基转移酶,对 H3K18 甲基化至关重要,它调节恶性疟原虫血液阶段的核酸代谢过程,是全面染色质调节网络的一部分。重要意义DNA 复制和转录的微调调节对快速繁殖的血液阶段疟疾寄生虫尤为重要,参与这些过程的蛋白质是重要的药物靶标。这项研究表明,与之前的报道相反,恶性疟原虫的组蛋白甲基转移酶 PfSET10 能促进组蛋白 3 赖氨酸 K18 的甲基化,而迄今为止人们对这种组蛋白标记还不甚了解。基因敲除导致的 PfSET10 缺乏会影响参与红细胞内发育的基因。此外,在血期寄生虫的细胞核中,PfSET10 与对 DNA 复制、重塑和修复以及转录调控和 mRNA 处理至关重要的各种蛋白复合物相互作用。总之,本研究强调了 PfSET10 是一种影响 H3K18 甲基化的甲基转移酶,在恶性疟原虫在红细胞中的发育过程中对染色质的维持具有关键作用。
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引用次数: 0
Mouse innate resistance to Neospora caninum infection is driven by early production of IFNγ by NK cells in response to parasite ligands. [公式:见正文]小鼠对犬新孢子虫感染的先天抵抗力是由 NK 细胞对寄生虫配体早期产生的 IFNγ 驱动的。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-24 DOI: 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}
引用次数: 0
The Plasmodium falciparum histone methyltransferase PfSET10 is dispensable for the regulation of antigenic variation and gene expression in blood-stage parasites. 恶性疟原虫组蛋白甲基转移酶PfSET10对于血期寄生虫抗原变异和基因表达的调控是不可或缺的。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-24 DOI: 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
恶性疟原虫利用毒力因子恶性疟原虫红细胞膜蛋白 1(PfEMP1)的抗原变异来逃避血液感染过程中的适应性免疫反应。PfEMP1 的抗原变异是通过多拷贝变异基因家族各成员互斥表达的表观遗传开关发生的。单个 var 基因的激活与基因座重新定位到核外围的专用区域以及启动子区域组蛋白 3 赖氨酸 4 二/三甲基化(H3K4me2/3)和 H3K9 乙酰化标记的沉积有关。之前的研究发现,推测的 H3K4 特异性甲基转移酶 PfSET10 是变异基因表达的必需酶和正调控因子,但最近的一项研究报告了相互矛盾的数据。在这里,我们利用迭代基因组编辑技术设计了一个条件性 PfSET10 基因敲除品系,以研究 PfSET10 在 var 基因调控中的功能。我们证明,PfSET10 并不是相互排斥的变异基因表达和切换所必需的。我们还发现,PfSET10 不仅对无性寄生虫的增殖是不可或缺的,而且对有性转化和配子细胞分化也是不可或缺的。此外,RNA-seq 比较实验显示,PfSET10 在无性寄生虫发育和配子细胞发生过程中没有明显的基因表达调控作用。但有趣的是,PfSET10 在无性寄生虫和有性寄生虫中显示出不同的核下定位模式,并在成熟配子细胞中显示出雌性特异性表达。总之,我们的工作详细证实了 PfSET10 不参与调节变异基因的表达,也不是血期寄生虫存活所必需的,这表明 PfSET10 可能对蚊媒的生命周期进展或肝脏阶段的发育很重要。为了在人体血液中生存和繁殖,寄生虫需要躲避宿主免疫系统的识别。为此,恶性疟原虫可以通过一种叫做抗原变异的过程来改变表面抗原的表达。这种引人入胜的生存策略是基于变异多基因家族中单个成员表达的不频繁切换。以前的研究报告称,表观遗传调节因子 PfSET10 在控制相互排斥的变异基因表达和切换中的作用存在相互矛盾的结果。在这里,我们明确证明了 PfSET10 既不需要抗原变异,也不需要在血期感染过程中表达任何其他蛋白。这一信息对于引导我们探索控制抗原变异的其他分子机制以及研究 PfSET10 在其他生命周期阶段的功能至关重要。
{"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":"&lt;p&gt;&lt;p&gt;The malaria parasite &lt;i&gt;Plasmodium falciparum&lt;/i&gt; employs antigenic variation of the virulence factor &lt;i&gt;P. falciparum&lt;/i&gt; 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 &lt;i&gt;var&lt;/i&gt; gene family. &lt;i&gt;var&lt;/i&gt; genes are located in perinuclear clusters of transcriptionally inactive heterochromatin. Singular &lt;i&gt;var&lt;/i&gt; 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 &lt;i&gt;var&lt;/i&gt; 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 &lt;i&gt;var&lt;/i&gt; gene regulation. We demonstrate that PfSET10 is not required for mutually exclusive &lt;i&gt;var&lt;/i&gt; 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 &lt;i&gt;var&lt;/i&gt; 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 &lt;i&gt;Plasmodium falciparum&lt;/i&gt; 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, &lt;i&gt;P. falciparum&lt;/i&gt; can change the expression of surface antigens &lt;i&gt;via&lt;/i&gt; a process called antigenic variation. This fascinating survival strategy is based on infrequent switches in the expression of single members of the &lt;i&gt;var&lt;/i&gt; multigene family. Previous research reported conflicting results on the role of the epigenetic regulator PfSET10 in controlling mutually exclusive &lt;i&gt;var&lt;/i&gt; 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}
引用次数: 0
Candida glabrata maintains two HAP1 ohnologs, HAP1A and HAP1B, for distinct roles in ergosterol gene regulation to mediate sterol homeostasis under azole and hypoxic conditions. 白色念珠菌有两个 HAP1 同源物,即 HAP1A 和 HAP1B,它们在麦角甾醇基因调控中发挥不同的作用,在偶氮唑和缺氧条件下介导甾醇平衡。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-23 DOI: 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.

胶状念珠菌(Candida glabrata)对唑类抗真菌药物具有先天耐药性,但也有迅速产生临床耐药性的倾向。针对 Erg11 的唑类药物是治疗念珠菌感染的主要抗真菌药物之一。尽管唑类药物被广泛使用,但控制唑类药物诱导的 ERG 基因表达和光滑念珠菌耐药性的机制主要围绕着 Upc2 和/或 Pdr1。系统发育和同源分析表明,在全基因组复制事件后,草履虫保留了 HAP1A 和 HAP1B,而酿酒酵母只保留了 HAP1A 的直向同源物 HAP1。在这项研究中,我们确定了两个锌簇转录因子 Hap1A 和 Hap1B 作为 ERG 基因直接调控因子的功能。在 S. cerevisiae 中,Hap1A 的同源物 Hap1 是一种已知的转录因子,在有氧和缺氧条件下控制 ERG 基因的表达。有趣的是,在 S. cerevisiae 或 C. glabrata 中分别删除 HAP1 或 HAP1B 会改变对唑类的敏感性。相比之下,缺失 HAP1A 的菌株对唑类没有敏感性。我们还确定,hap1BΔ菌株的唑敏感性增加是由于唑诱导的ERG基因表达减少,导致麦角甾醇总量减少。令人惊讶的是,在有氧条件下几乎检测不到 Hap1A 蛋白的表达,但在缺氧条件下,Hap1A 蛋白会被特异性诱导,而在缺氧条件下,Hap1A 是抑制 ERG 基因所必需的。然而,在缺乏 Hap1A 的情况下,Hap1B 可以作为转录抑制因子进行补偿。我们的研究表明,Hap1A和Hap1B可被C. glabrata利用来适应特定的宿主和环境条件:侵袭性和耐药性真菌感染是一个重大的公共卫生问题。由于对唑类抗真菌药物的固有耐药性及其产生临床耐药性的能力,人类真菌病原体--白色念珠菌往往难以治疗。因此,了解促进真菌生长和环境适应的途径可能会发现新的药物靶点和/或更有效的抗真菌疗法。虽然对念珠菌的唑类抗药性机制进行了广泛的研究,但迄今为止,锌簇转录因子(如 Hap1A 和 Hap1B)在草绿色念珠菌中的作用在很大程度上仍未得到探索。我们的研究表明,在唑类药物治疗和限氧生长条件下,这些因子在调节麦角固醇稳态方面发挥着独特而关键的作用。这些发现为我们了解这种病原体如何适应不同的环境条件提供了新的视角,并加深了我们对改变药物敏感性和/或耐药性的因素的理解。
{"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}
引用次数: 0
A whole-cell pertussis vaccine engineered to elicit reduced reactogenicity protects baboons against pertussis challenge. 一种全细胞百日咳疫苗可降低反应性,保护狒狒免受百日咳挑战。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-23 DOI: 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。
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引用次数: 0
Diversity of Campylobacter spp. circulating in a rhesus macaque (Macaca mulatta) breeding colony using culture and molecular methods. 利用培养和分子方法研究猕猴繁殖群中弯曲杆菌属循环的多样性。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-23 DOI: 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.</
空肠弯曲菌和大肠弯曲菌是导致人类细菌性肠胃炎的主要原因,感染后会产生感染后肠易激综合征(PI-IBS)。猕猴(Macaca mulatta)同样容易感染急性弯曲杆菌病,是潜在的肠易激综合征模型。我们利用培养、qPCR 和全基因组测序(WGS)鉴定了猕猴繁殖群中循环的弯曲杆菌种类。我们还比较了用 qPCR 检测到的空肠弯曲菌和大肠弯曲菌在马铃薯种群中的流行率与培养率,并确定了细菌存在和肠道疾病的风险因素。275 份样本的培养结果显示,大肠杆菌(103 例)和空肠杆菌(8 例)对喹诺酮类药物耐药,其中 21.6% 对喹诺酮类药物耐药,3.6% 对大环内酯类药物耐药。耐多种药物的分离物仅来自腹泻或经组织学证实患有慢性小肠结肠炎的动物。除氨基糖苷类药物外,耐药性基因型预测非常准确。所有测序分离物都含有细胞致死性膨胀毒素所有亚单位的基因。qPCR 检测出大肠弯曲杆菌的感染率为 45.9%,空肠弯曲杆菌的感染率为 29.6%。与健康动物相比,患有肠道疾病的动物体内这两种细菌的数量都明显较高(P < 0.05),但只有年龄较小的动物与弯曲杆菌或肠道疾病有明显关联。用 qPCR 法检测到的空肠弯曲菌阳性动物明显多于用培养法检测到的空肠弯曲菌阳性动物。这些结果提供了在美国马铃薯种群中循环的弯曲杆菌属的综合特征,并表明 qPCR 在检测马铃薯中的空肠弯曲杆菌方面更具优势:胃肠道疾病是非人灵长类动物群最常见的住院原因之一,占非研究性安乐死的三分之一以上。在猕猴中,这种疾病表现为急性腹泻和慢性小肠结肠炎(CE),这是一种慢性腹泻综合症,会导致体重增长缓慢或体重减轻,对治疗反应微弱。弯曲杆菌属是导致猕猴急性肠炎的主要原因,可能会导致个体患上慢性肠炎,类似于人类的感染后肠易激综合征。尽管存在这些问题,但有关猕猴群体中弯曲杆菌特征的研究却很少,特别是利用全基因组测序和评估宿主健康状况的研究。我们的研究结果提供了对猕猴群中循环的弯曲杆菌菌株的深入了解,这可以改善临床监测,协助治疗决策,并为弯曲杆菌病作为 CE 的催化剂提供了新的研究途径。
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引用次数: 0
First insights into the prevalence, genetic characteristics, and pathogenicity of Bacillus cereus from generations worldwide. 首次了解全球各代蜡样芽孢杆菌的流行情况、遗传特征和致病性。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-23 DOI: 10.1128/msphere.00702-24
Cuihong Tong, Danyu Xiao, Qi Li, Jing Gou, Shuang Wang, Zhenling Zeng, Wenguang Xiong

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.

蜡样芽孢杆菌是一种全球性威胁,是毒素引发食源性疾病的主要原因之一。然而,目前仍缺乏对蜡样芽孢杆菌在全球的流行情况和特征的全面评估。在此,我们对 1900 年代至 2022 年在非洲、美洲、亚洲、欧洲和大洋洲收集到的 191 株蜡样芽孢杆菌进行了全基因组序列分析,发现 CC142 在全球蜡样芽孢杆菌克隆复合体中占主导地位。研究结果提供了直接证据,证明蜡样芽孢杆菌可通过食物链和洲际传播。全球不同世代的蜡样芽孢杆菌在抗生素耐药基因、毒力和生物膜基因图谱方面表现出一致性,但基因组异质性较高。我们强调,蜡样芽孢杆菌将对全球公共卫生和临床治疗构成严峻挑战。这项研究首次利用全基因组序列分析,强调了从 20 世纪到 2022 年蜡样芽孢杆菌在全球的流行情况、遗传特征和致病性。CC142在全球蜡样芽孢杆菌克隆复合体中占主导地位。此外,我们还发现不同来源的分离株之间存在密切的进化关系。全球不同世代的蜡样芽孢杆菌分离物在潜在致病性方面表现出一致性,但基因组异质性较高。我们强调,蜡样芽孢杆菌将对全球公共卫生和临床治疗构成严峻挑战。
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引用次数: 0
Erratum for Hasan et al., "Role of glycogen metabolism in Clostridioides difficile virulence". 对 Hasan 等人 "艰难梭菌毒力中糖原代谢的作用 "的更正。
IF 3.7 2区 生物学 Q2 MICROBIOLOGY Pub Date : 2024-10-22 DOI: 10.1128/msphere.00835-24
Md Kamrul Hasan, Marjorie Pizarro-Guajardo, Javier Sanchez, Revathi Govind
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引用次数: 0
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