Actinobacillus pleuropneumoniae is the causative agent of pleuropneumonia in swine, a highly contagious and economically significant disease. The genetic variability of A. pleuropneumoniae complicates disease control efforts, as it enables rapid adaptation to various stressors, including antimicrobial treatments. To better understand the molecular mechanisms underlying this adaptability, we investigated the role of the bacterial defensome and its relationship with mobile genetic elements (MGEs), such as prophages, plasmids, and integrative conjugative elements (ICEs). Using bioinformatic tools, we identified a diverse and rich defensome in A. pleuropneumoniae, with an average of 16 different defense systems per strain. We found that CRISPR-Cas systems, along with other defense mechanisms, are actively involved in restricting the entry of foreign genetic material, playing a crucial role in bacterial adaptation. Additionally, we characterized several novel prophages and examined their distribution across different strains, revealing their potential contribution to the bacterium's evolutionary success. Our findings underscore the complex interplay between the bacterium's defense systems and MGEs, shedding light on how A. pleuropneumoniae maintains genetic diversity while also safeguarding itself against external threats. These insights provide a better understanding of the genetic factors that influence the pathogen's adaptability and highlight potential avenues for more effective disease control strategies.
{"title":"The Arms Race Between Actinobacillus pleuropneumoniae and Its Genetic Environment: A Comprehensive Analysis of Its Defensome and Mobile Genetic Elements","authors":"Giarlã Cunha da Silva, Ciro César Rossi","doi":"10.1111/mmi.15374","DOIUrl":"https://doi.org/10.1111/mmi.15374","url":null,"abstract":"<i>Actinobacillus pleuropneumoniae</i> is the causative agent of pleuropneumonia in swine, a highly contagious and economically significant disease. The genetic variability of <i>A. pleuropneumoniae</i> complicates disease control efforts, as it enables rapid adaptation to various stressors, including antimicrobial treatments. To better understand the molecular mechanisms underlying this adaptability, we investigated the role of the bacterial defensome and its relationship with mobile genetic elements (MGEs), such as prophages, plasmids, and integrative conjugative elements (ICEs). Using bioinformatic tools, we identified a diverse and rich defensome in <i>A. pleuropneumoniae</i>, with an average of 16 different defense systems per strain. We found that CRISPR-Cas systems, along with other defense mechanisms, are actively involved in restricting the entry of foreign genetic material, playing a crucial role in bacterial adaptation. Additionally, we characterized several novel prophages and examined their distribution across different strains, revealing their potential contribution to the bacterium's evolutionary success. Our findings underscore the complex interplay between the bacterium's defense systems and MGEs, shedding light on how <i>A. pleuropneumoniae</i> maintains genetic diversity while also safeguarding itself against external threats. These insights provide a better understanding of the genetic factors that influence the pathogen's adaptability and highlight potential avenues for more effective disease control strategies.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"109 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901813","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}
Brian Nguyen, Carly Ching, Ashley MacGuire, Pranav Casula, Connor Newman, Faith Finley, Veronica G. Godoy
Acinetobacter baumannii is an opportunistic pathogen causing several infections that are increasingly difficult to treat due to its ability to rapidly gain antibiotic resistances. These resistances can arise due to mutations through the activity of error-prone DNA polymerases, such as DNA polymerase V (DNA Pol V) in response to DNA damage. The regulation of the DNA damage response (DDR) in A. baumannii is not completely understood; the regulation of genes encoding multiple copies of DNA Pol V is not fully characterized. Through genome-wide mutagenesis, we have identified a novel TetR-like family regulator of the umuDC and umuC genes, which we have named Error-prone polymerase regulator (EppR). We have found that EppR represses the expression of the genes encoding DNA Pol V and itself through direct binding to an EppR motif in their promoters. Lastly, we show that EppR also regulates UmuDAb, previously identified as a regulator of genes encoding DNA Pol V. These two gene products are functionally required to ensure regulation of the expression of the two umuDC, the two umuC genes as well as the regulators umuDAb and eppR genes. With these results, we propose a model in which multiple transcription factors regulate the expression of all these genes.
鲍曼不动杆菌是一种机会致病菌，引起多种感染，由于其迅速获得抗生素耐药性的能力，这种感染越来越难以治疗。这些抗性可能是由于易出错的DNA聚合酶（如DNA聚合酶V (DNA Pol V)）响应DNA损伤而产生的突变而产生的。鲍曼不动杆菌DNA损伤反应（DDR）的调控机制尚不完全清楚；编码DNA多拷贝Pol V的基因调控尚未完全确定。通过全基因组诱变，我们鉴定出了umuDC和umuC基因的一种新的类似于rt的家族调节剂，我们将其命名为易出错聚合酶调节剂（Error-prone polymerase regulator, EppR）。我们发现EppR通过直接结合启动子中的EppR基序来抑制编码DNA Pol V及其自身的基因的表达。最后，我们发现EppR还能调控UmuDAb，而UmuDAb先前被认为是编码DNA Pol v的基因的调节因子。这两个基因产物在功能上是必需的，以确保调控两个umuDC、两个umuC基因以及调节因子UmuDAb和EppR基因的表达。根据这些结果，我们提出了一个模型，其中多个转录因子调节所有这些基因的表达。
{"title":"Identification of EppR, a Second Repressor of Error-Prone DNA Polymerase Genes in Acinetobacter baumannii","authors":"Brian Nguyen, Carly Ching, Ashley MacGuire, Pranav Casula, Connor Newman, Faith Finley, Veronica G. Godoy","doi":"10.1111/mmi.15368","DOIUrl":"https://doi.org/10.1111/mmi.15368","url":null,"abstract":"<i>Acinetobacter baumannii</i> is an opportunistic pathogen causing several infections that are increasingly difficult to treat due to its ability to rapidly gain antibiotic resistances. These resistances can arise due to mutations through the activity of error-prone DNA polymerases, such as DNA polymerase V (DNA Pol V) in response to DNA damage. The regulation of the DNA damage response (DDR) in <i>A. baumannii</i> is not completely understood; the regulation of genes encoding multiple copies of DNA Pol V is not fully characterized. Through genome-wide mutagenesis, we have identified a novel TetR-like family regulator of the <i>umuDC</i> and <i>umuC</i> genes, which we have named Error-prone polymerase regulator (EppR). We have found that EppR represses the expression of the genes encoding DNA Pol V and itself through direct binding to an EppR motif in their promoters. Lastly, we show that EppR also regulates UmuDAb, previously identified as a regulator of genes encoding DNA Pol V. These two gene products are functionally required to ensure regulation of the expression of the two <i>umuDC</i>, the two <i>umuC</i> genes as well as the regulators <i>umuDAb</i> and <i>eppR</i> genes. With these results, we propose a model in which multiple transcription factors regulate the expression of all these genes.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"41 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849527","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}
Biofilms are highly organized, cooperating communities of microorganisms encased in a self-produced extracellular matrix, providing resilience against external stress such as antimicrobial agents and host defenses. A hallmark of biofilms is their phenotypic heterogeneity, which enhances the overall growth and survival of the community. In this study, we demonstrate that removing the dnaK and tig genes encoding the core molecular chaperones DnaK (Hsp70 homolog) and Trigger factor disrupted protein homeostasis in Bacillus subtilis and resulted in the formation of an extremely mucoid biofilm with aberrant architecture, compromised structural integrity, and altered phenotypic heterogeneity. These changes include a large reduction in the motile subpopulation and an overrepresentation of matrix producers and endospores. Overproduction of poly-γ-glutamic acid contributed crucially to the mucoid phenotype and aberrant biofilm architecture. Homeostasis impairment, triggered by elevated temperatures, in wild-type cells led to mucoid and aberrant biofilm phenotypes similar to those observed in strains lacking both dnaK and tig. Our findings show that disruption of protein homeostasis, whether due to the absence of molecular chaperones or because of environmental factors, severely changes biofilm features.
{"title":"Protein Homeostasis Impairment Alters Phenotypic Heterogeneity of Biofilm Communities","authors":"Judith Matavacas, Claes von Wachenfeldt","doi":"10.1111/mmi.15366","DOIUrl":"https://doi.org/10.1111/mmi.15366","url":null,"abstract":"Biofilms are highly organized, cooperating communities of microorganisms encased in a self-produced extracellular matrix, providing resilience against external stress such as antimicrobial agents and host defenses. A hallmark of biofilms is their phenotypic heterogeneity, which enhances the overall growth and survival of the community. In this study, we demonstrate that removing the <i>dnaK</i> and <i>tig</i> genes encoding the core molecular chaperones DnaK (Hsp70 homolog) and Trigger factor disrupted protein homeostasis in <i>Bacillus subtilis</i> and resulted in the formation of an extremely mucoid biofilm with aberrant architecture, compromised structural integrity, and altered phenotypic heterogeneity. These changes include a large reduction in the motile subpopulation and an overrepresentation of matrix producers and endospores. Overproduction of poly-γ-glutamic acid contributed crucially to the mucoid phenotype and aberrant biofilm architecture. Homeostasis impairment, triggered by elevated temperatures, in wild-type cells led to mucoid and aberrant biofilm phenotypes similar to those observed in strains lacking both <i>dnaK</i> and <i>tig</i>. Our findings show that disruption of protein homeostasis, whether due to the absence of molecular chaperones or because of environmental factors, severely changes biofilm features.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"63 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841627","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}
Arnau Galan, Natalya Kraeva, Kristína Záhonová, Anzhelika Butenko, Alexei Yu Kostygov, Zdeněk Paris, Jiří Pergner, Claretta Bianchi, Fadel Fakih, Andreu Saura, Julius Lukeš, Vyacheslav Yurchenko
Blastocrithidia nonstop is a protist with a highly unusual nuclear genetic code, in which all three standard stop codons are reassigned to encode amino acids, with UAA also serving as a sole termination codon. In this study, we demonstrate that this parasitic flagellate is amenable to genetic manipulation, enabling gene ablation and protein tagging. Using preassembled Cas9 ribonucleoprotein complexes, we successfully disrupted and tagged the non-essential gene encoding catalase. These advances establish this single-celled eukaryote as a model organism for investigating the malleability and evolution of the genetic code in eukaryotes.
{"title":"Converting Blastocrithidia Nonstop, a Trypanosomatid With Non-Canonical Genetic Code, Into a Genetically-Tractable Model","authors":"Arnau Galan, Natalya Kraeva, Kristína Záhonová, Anzhelika Butenko, Alexei Yu Kostygov, Zdeněk Paris, Jiří Pergner, Claretta Bianchi, Fadel Fakih, Andreu Saura, Julius Lukeš, Vyacheslav Yurchenko","doi":"10.1111/mmi.15365","DOIUrl":"https://doi.org/10.1111/mmi.15365","url":null,"abstract":"<i>Blastocrithidia nonstop</i> is a protist with a highly unusual nuclear genetic code, in which all three standard stop codons are reassigned to encode amino acids, with UAA also serving as a sole termination codon. In this study, we demonstrate that this parasitic flagellate is amenable to genetic manipulation, enabling gene ablation and protein tagging. Using preassembled Cas9 ribonucleoprotein complexes, we successfully disrupted and tagged the non-essential gene encoding catalase. These advances establish this single-celled eukaryote as a model organism for investigating the malleability and evolution of the genetic code in eukaryotes.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"3 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813997","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}
Momoko Ito, Hideharu Yukitake, Paul D. Veith, Dhana G. Gorasia, Takashi Tominaga, Yuko Sasaki, Eric C. Reynolds, Koji Nakayama, Mariko Naito, Mikio Shoji
Porphyromonas gingivalis is an important bacterium associated with chronic periodontitis. The type IX secretion system (T9SS) in P. gingivalis secretes conserved C-terminal domain (CTD) containing proteins, which are also called T9SS cargo proteins, including gingipain proteinases, to the cell surface and extracellular milieu. We have shown that gene expression of some T9SS component proteins is regulated by a two-component regulatory system, PorX-PorY, an ECF sigma factor, SigP, and a T9SS cargo protein, PorA. As PorA has its own CTD, PorA is mainly localized as an A-LPS-bound form and PorV-bound form on the cell surface. However, it remains unclear how PorA can activate the PorXY-SigP signaling cascade. In this study, our results revealed that the CTD of PorA can activate the PorXY-SigP signaling cascade via interaction with PorY. It is well known that the canonical role of CTD is to act as a secretion signal for T9SS protein export. In here, we propose a novel concept that the CTD of PorA can play a dual role: as a secretion signal directing the secretion of PorA and as a positive regulator of T9SS gene expression by binding to PorY in the periplasm.
牙龈卟啉单胞菌是一种与慢性牙周炎相关的重要细菌。牙龈卟啉单胞菌的九型分泌系统（T9SS）向细胞表面和细胞外环境分泌含有保守的 C-末端结构域（CTD）的蛋白，这些蛋白也被称为 T9SS 货物蛋白，包括牙龈蛋白酶。我们的研究表明，一些 T9SS 组成蛋白的基因表达受双组分调控系统 PorX-PorY、ECF 西格玛因子 SigP 和 T9SS 货物蛋白 PorA 的调控。由于 PorA 有自己的 CTD，因此 PorA 主要以 A-LPS 结合型和 PorV 结合型的形式定位于细胞表面。然而，目前仍不清楚 PorA 如何激活 PorXY-SigP 信号级联。本研究的结果显示，PorA 的 CTD 可通过与 PorY 的相互作用激活 PorXY-SigP 信号级联。众所周知，CTD 的典型作用是作为 T9SS 蛋白质输出的分泌信号。在本文中，我们提出了一个新的概念，即 PorA 的 CTD 可以发挥双重作用：作为分泌信号指导 PorA 的分泌，以及通过与外质中的 PorY 结合成为 T9SS 基因表达的正向调节因子。
{"title":"PorA of the Type IX Secretion Is a Ligand of the PorXY Two-Component Regulatory System in Porphyromonas gingivalis","authors":"Momoko Ito, Hideharu Yukitake, Paul D. Veith, Dhana G. Gorasia, Takashi Tominaga, Yuko Sasaki, Eric C. Reynolds, Koji Nakayama, Mariko Naito, Mikio Shoji","doi":"10.1111/mmi.15363","DOIUrl":"https://doi.org/10.1111/mmi.15363","url":null,"abstract":"<i>Porphyromonas gingivalis</i> is an important bacterium associated with chronic periodontitis. The type IX secretion system (T9SS) in <i>P. gingivalis</i> secretes conserved C-terminal domain (CTD) containing proteins, which are also called T9SS cargo proteins, including gingipain proteinases, to the cell surface and extracellular milieu. We have shown that gene expression of some T9SS component proteins is regulated by a two-component regulatory system, PorX-PorY, an ECF sigma factor, SigP, and a T9SS cargo protein, PorA. As PorA has its own CTD, PorA is mainly localized as an A-LPS-bound form and PorV-bound form on the cell surface. However, it remains unclear how PorA can activate the PorXY-SigP signaling cascade. In this study, our results revealed that the CTD of PorA can activate the PorXY-SigP signaling cascade via interaction with PorY. It is well known that the canonical role of CTD is to act as a secretion signal for T9SS protein export. In here, we propose a novel concept that the CTD of PorA can play a dual role: as a secretion signal directing the secretion of PorA and as a positive regulator of T9SS gene expression by binding to PorY in the periplasm.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797989","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}
Yeast flocculation relies on cell surface flocculin proteins encoded by the sub-telomeric gene, FLO1. The expression of FLO1 is antagonistically regulated by the Tup1-Cyc8 repressor complex and the Swi-Snf co-activator complexes. The role of hyperacetylated N-terminal amino acid residues of histone H3 and H4 is well established in the transcription of FLO1 and other Tup1-Cyc8 regulated genes. However, sub-domains within the tails of histone H3 and H4 are yet to be identified and the mechanism by which they regulate the FLO1 transcription is completely unexplored. Upon screening of different H3 and H4 N-terminal stretch deletion mutants, we have identified a new region within the N-terminal tail of histone H3, H3Δ(17–24) regulating the transcription of FLO1 and FLO5. This N-terminal truncation mutant showed higher FLO1 and FLO5 expression by 68% and 41% respectively compared to wild-type H3. Further examination showed reduced Cyc8 and nucleosome occupancy in the upstream regulatory region of active flo1 in the H3Δ(17–24) mutant than in H3 wild-type cells. The findings also indicate that Hda1 assists in Cyc8 interaction at the active FLO1 template. Altogether we demonstrate that Tup1-independent interaction of Cyc8 with the active FLO1 gene acts as a transcription limiting factor and that the histone H3 N-terminal 17–24 stretch is essential for this interaction. In the absence of the 17–24 stretch, the Cyc8 restrictive effect is altered, resulting in over-expression of FLO1.
{"title":"An Uncharacterized Domain Within the N-Terminal Tail of Histone H3 Regulates the Transcription of FLO1 via Cyc8","authors":"Ranu Singh, Raghuvir Singh Tomar","doi":"10.1111/mmi.15362","DOIUrl":"https://doi.org/10.1111/mmi.15362","url":null,"abstract":"Yeast flocculation relies on cell surface flocculin proteins encoded by the sub-telomeric gene, <i>FLO1</i>. The expression of <i>FLO1</i> is antagonistically regulated by the Tup1-Cyc8 repressor complex and the Swi-Snf co-activator complexes. The role of hyperacetylated N-terminal amino acid residues of histone H3 and H4 is well established in the transcription of <i>FLO1</i> and other Tup1-Cyc8 regulated genes. However, sub-domains within the tails of histone H3 and H4 are yet to be identified and the mechanism by which they regulate the <i>FLO1</i> transcription is completely unexplored. Upon screening of different H3 and H4 N-terminal stretch deletion mutants, we have identified a new region within the N-terminal tail of histone H3, H3Δ(17–24) regulating the transcription of <i>FLO1</i> and <i>FLO5</i>. This N-terminal truncation mutant showed higher <i>FLO1</i> and <i>FLO5</i> expression by 68% and 41% respectively compared to wild-type H3. Further examination showed reduced Cyc8 and nucleosome occupancy in the upstream regulatory region of active <i>flo1</i> in the H3Δ(17–24) mutant than in H3 wild-type cells. The findings also indicate that Hda1 assists in Cyc8 interaction at the active <i>FLO1</i> template. Altogether we demonstrate that Tup1-independent interaction of Cyc8 with the active <i>FLO1</i> gene acts as a transcription limiting factor and that the histone H3 N-terminal 17–24 stretch is essential for this interaction. In the absence of the 17–24 stretch, the Cyc8 restrictive effect is altered, resulting in over-expression of <i>FLO1</i>.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"4 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798390","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}
Sara Moutacharrif, Feth El Zahar Haichar, Sam Meyer, Cecile Ribot, Sylvie Reverchon, William Nasser, Florence Hommais
In bacteria, the regulation of gene expression involves complex networks that integrate both transcriptional and posttranscriptional mechanisms. At the transcriptional level, nucleoid-associated proteins (NAPs) such as H-NS, HU, Lrp, IHF, Fis and Hfq are key players as they not only compact bacterial DNA but also regulate transcription. Small noncoding RNAs (sRNAs), on the other hand, are known to affect bacterial gene expression posttranscriptionally by base pairing with the target mRNA, but they can also be involved in nucleoid condensation. Interestingly, certain NAPs also influence the function of sRNAs and, conversely, sRNAs themselves can modulate the activity of NAPs, creating a complex bidirectional regulatory network. Here, we summarise the current knowledge of the major NAPs, focusing on the specific role of Hfq. Examples of the regulation of NAPs by sRNAs, the regulation of sRNAs by NAPs and the role of sRNAs in nucleoid structuring are also discussed. This review focuses on the cross-talk between NAPs and sRNAs in an attempt to understand how this interplay works to orchestrate the functioning of the cell.
{"title":"The Power Duo: How the Interplay Between Nucleoid-Associated Proteins and Small Noncoding RNAs Orchestrates the Cellular Regulatory Symphony","authors":"Sara Moutacharrif, Feth El Zahar Haichar, Sam Meyer, Cecile Ribot, Sylvie Reverchon, William Nasser, Florence Hommais","doi":"10.1111/mmi.15359","DOIUrl":"https://doi.org/10.1111/mmi.15359","url":null,"abstract":"In bacteria, the regulation of gene expression involves complex networks that integrate both transcriptional and posttranscriptional mechanisms. At the transcriptional level, nucleoid-associated proteins (NAPs) such as H-NS, HU, Lrp, IHF, Fis and Hfq are key players as they not only compact bacterial DNA but also regulate transcription. Small noncoding RNAs (sRNAs), on the other hand, are known to affect bacterial gene expression posttranscriptionally by base pairing with the target mRNA, but they can also be involved in nucleoid condensation. Interestingly, certain NAPs also influence the function of sRNAs and, conversely, sRNAs themselves can modulate the activity of NAPs, creating a complex bidirectional regulatory network. Here, we summarise the current knowledge of the major NAPs, focusing on the specific role of Hfq. Examples of the regulation of NAPs by sRNAs, the regulation of sRNAs by NAPs and the role of sRNAs in nucleoid structuring are also discussed. This review focuses on the cross-talk between NAPs and sRNAs in an attempt to understand how this interplay works to orchestrate the functioning of the cell.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"20 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784728","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 : 2025-04-01Epub Date: 2025-02-13DOI: 10.1111/mmi.15346
Victor Combret, Isabelle Rincé, Ronan Cochelin, Florie Desriac, Cécile Muller, Diane Soussan, Axel Hartke, Josef Deutscher, Nicolas Sauvageot
Two PTS transporters involved in the uptake of cellobiose and short cellooligosaccharides were identified in Enterococcus faecalis. Genes coding for the different EII proteins are found in a locus composed of three operonic structures expressing two distinct EIIC (CelC1 and CelC2), two identical EIIB (CelB1 and CelB2) and a unique EIIA (CelA1). The EIIA plays a central role in β-glucoside uptake because it is required not only for β-homodiholosides but also for the diheteroside N-acetylglucosamine-L-asparagine. Depending on their size, cellooligosaccharides are preferably transported either by CelC1 (di-saccharides) or by CelC2 (4 glycosidic residues and more), with tri-saccharides being taken up by both EIIC transporters. Moreover, CelA1B2C2 require CelGHI to be functional, three small proteins, the function of which remains unknown. CelA1B1C1 is the main but not exclusive transporter of cellobiose and chitobiose. It is involved in the transport of other β-glucodisaccharides, such as laminaribiose and sophorose. This PTS can be complemented by other transporters highlighting the existence of a network for β-glucoside uptake. This locus is under the control of CelR, a LevR-like transcription activator.
在粪肠球菌中发现了两种参与纤维二糖和短纤维低聚糖摄取的PTS转运蛋白。编码不同EII蛋白的基因位于一个由三个操纵子结构组成的位点上，表达两种不同的EIIC (CelC1和CelC2)，两种相同的EIIB （CelB1和CelB2）和一种独特的EIIA （CelA1）。EIIA在β-葡萄糖苷的摄取中起着核心作用，因为它不仅是β-纯二holoides所需要的，而且是二异糖n -乙酰氨基- l -天冬酰胺所需要的。根据它们的大小，纤维低聚糖最好通过CelC1（二糖）或CelC2（4个糖苷残基或更多）运输，三糖由两种EIIC转运蛋白吸收。此外，CelA1B2C2需要CelGHI发挥功能，这是三种小蛋白，其功能尚不清楚。CelA1B1C1是纤维素糖和壳聚糖的主要转运体，但不是唯一的转运体。它参与其他β-葡萄糖二糖的运输，如层糖糖和苦参糖。这种PTS可以由其他转运蛋白补充，强调β-葡萄糖苷摄取网络的存在。这个基因座受CelR的控制，CelR是一种类似levelr的转录激活因子。
{"title":"Cellodextrin Metabolism and Phosphotransferase System-Catalyzed Uptake in Enterococcus faecalis.","authors":"Victor Combret, Isabelle Rincé, Ronan Cochelin, Florie Desriac, Cécile Muller, Diane Soussan, Axel Hartke, Josef Deutscher, Nicolas Sauvageot","doi":"10.1111/mmi.15346","DOIUrl":"10.1111/mmi.15346","url":null,"abstract":"<p><p>Two PTS transporters involved in the uptake of cellobiose and short cellooligosaccharides were identified in Enterococcus faecalis. Genes coding for the different EII proteins are found in a locus composed of three operonic structures expressing two distinct EIIC (CelC1 and CelC2), two identical EIIB (CelB1 and CelB2) and a unique EIIA (CelA1). The EIIA plays a central role in β-glucoside uptake because it is required not only for β-homodiholosides but also for the diheteroside N-acetylglucosamine-L-asparagine. Depending on their size, cellooligosaccharides are preferably transported either by CelC1 (di-saccharides) or by CelC2 (4 glycosidic residues and more), with tri-saccharides being taken up by both EIIC transporters. Moreover, CelA1B2C2 require CelGHI to be functional, three small proteins, the function of which remains unknown. CelA1B1C1 is the main but not exclusive transporter of cellobiose and chitobiose. It is involved in the transport of other β-glucodisaccharides, such as laminaribiose and sophorose. This PTS can be complemented by other transporters highlighting the existence of a network for β-glucoside uptake. This locus is under the control of CelR, a LevR-like transcription activator.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"378-391"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marita Torrissen Mårli, Magnus Øverlie Arntzen, Jennie Ann Allred, Anna Teigen Schultheiss, Oddvar Oppegaard, Morten Kjos, Daniel Straume
Murein hydrolases (or peptidoglycan hydrolases) play diverse roles in bacteria, from controlled remodeling of the bacterial cell wall to lytic agents. In streptococci, some such hydrolases have been associated with competence-induced fratricide, a process where bacteria kill closely related cells to release DNA that can be taken up during natural transformation. Here, we characterize ScrM, a conserved competence-induced murein hydrolase from Streptococcus dysgalactiae comprising a CHAP domain, an SH3b domain, and an uncharacterized C-terminal domain (CCD). ScrM displayed lytic activity against pyogenic and salivarius group streptococci. Microscopy analysis of fluorescent fusions revealed that ScrM specifically localizes to midcell of sensitive cells, with binding and localization mediated primarily by CCD. Upon competence induction, cells became immune to ScrM due to expression of ScrI, a Fem-transferase-like protein. We show by LC–MS/MS that ScrI incorporates Thr in place of Ala into the interpeptide bridges of peptidoglycan, which in turn prevents ScrM binding to midcell, thereby protecting the cells from self-lysis during competence. ScrM and ScrI are conserved among pyogenic streptococcal pathogens and represent new players in the cell wall biogenesis of these bacteria that may form a platform for the development of novel antimicrobial strategies.
{"title":"Self-Immunity Towards a Novel Competence-Induced Streptococcal Peptidoglycan Hydrolase is Mediated by a Fem-Transferase-Like Protein","authors":"Marita Torrissen Mårli, Magnus Øverlie Arntzen, Jennie Ann Allred, Anna Teigen Schultheiss, Oddvar Oppegaard, Morten Kjos, Daniel Straume","doi":"10.1111/mmi.15361","DOIUrl":"https://doi.org/10.1111/mmi.15361","url":null,"abstract":"Murein hydrolases (or peptidoglycan hydrolases) play diverse roles in bacteria, from controlled remodeling of the bacterial cell wall to lytic agents. In streptococci, some such hydrolases have been associated with competence-induced fratricide, a process where bacteria kill closely related cells to release DNA that can be taken up during natural transformation. Here, we characterize ScrM, a conserved competence-induced murein hydrolase from <i>Streptococcus dysgalactiae</i> comprising a CHAP domain, an SH3b domain, and an uncharacterized C-terminal domain (CCD). ScrM displayed lytic activity against pyogenic and salivarius group streptococci. Microscopy analysis of fluorescent fusions revealed that ScrM specifically localizes to midcell of sensitive cells, with binding and localization mediated primarily by CCD. Upon competence induction, cells became immune to ScrM due to expression of ScrI, a Fem-transferase-like protein. We show by LC–MS/MS that ScrI incorporates Thr in place of Ala into the interpeptide bridges of peptidoglycan, which in turn prevents ScrM binding to midcell, thereby protecting the cells from self-lysis during competence. ScrM and ScrI are conserved among pyogenic streptococcal pathogens and represent new players in the cell wall biogenesis of these bacteria that may form a platform for the development of novel antimicrobial strategies.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"58 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734440","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}
Ella J. Gehrke, Tejram Sahu, Krishna Sathya Manuguri, Christiane Voss, Godfree Mlambo, Beejan Asady, Maryam Saffarian, Julia D. Romano, Isabelle Coppens
Conserved across eukaryotic cells, Golgi reassembly and stacking proteins (GRASPs) are peripheral proteins that hold the flat cisternal membranes of the Golgi apparatus into stacks and that also play a role in a process of unconventional protein secretion involving the autophagy machinery. The Golgi in Plasmodium malaria parasites is composed of unstacked cisternae that contain a single GRASP homolog. We previously showed that the initial development of Plasmodium berghei in hepatocytes involves the clearance of micronemes through their sequestration into PbATG8-positive autophagosomes that fuse with the parasite plasma membrane. Here, we examine the involvement of PbGRASP in microneme elimination and extend our studies to assess the importance of GRASP for parasite development in the mammalian host and mosquito vector. GRASP associates with PbATG8 autophagosomes containing micronemes, though PbGRASP-KO parasites can expel micronemes. PbGRASP-KO parasites have no discernable phenotype during mosquito stage development or asexual blood stage growth. PbGRASP-KO liver stages form small schizonts at mid-infection, and then growth resumes. PbGRASP-KO hepatic merozoites egress from the mouse liver and induce higher parasitemia but display delayed and reduced cerebral malaria symptoms. These observations point to a regulatory role for GRASP in controlling parasite proliferation and virulence in mammalian hosts.
{"title":"The Plasmodium GRASP Homolog Modulates Liver Stage Development, Subsequent Blood Infection and Virulence in Mice","authors":"Ella J. Gehrke, Tejram Sahu, Krishna Sathya Manuguri, Christiane Voss, Godfree Mlambo, Beejan Asady, Maryam Saffarian, Julia D. Romano, Isabelle Coppens","doi":"10.1111/mmi.15360","DOIUrl":"https://doi.org/10.1111/mmi.15360","url":null,"abstract":"Conserved across eukaryotic cells, Golgi reassembly and stacking proteins (GRASPs) are peripheral proteins that hold the flat cisternal membranes of the Golgi apparatus into stacks and that also play a role in a process of unconventional protein secretion involving the autophagy machinery. The Golgi in <i>Plasmodium</i> malaria parasites is composed of unstacked cisternae that contain a single GRASP homolog. We previously showed that the initial development of <i>Plasmodium berghei</i> in hepatocytes involves the clearance of micronemes through their sequestration into PbATG8-positive autophagosomes that fuse with the parasite plasma membrane. Here, we examine the involvement of PbGRASP in microneme elimination and extend our studies to assess the importance of GRASP for parasite development in the mammalian host and mosquito vector. GRASP associates with PbATG8 autophagosomes containing micronemes, though PbGRASP-KO parasites can expel micronemes. PbGRASP-KO parasites have no discernable phenotype during mosquito stage development or asexual blood stage growth. PbGRASP-KO liver stages form small schizonts at mid-infection, and then growth resumes. PbGRASP-KO hepatic merozoites egress from the mouse liver and induce higher parasitemia but display delayed and reduced cerebral malaria symptoms. These observations point to a regulatory role for GRASP in controlling parasite proliferation and virulence in mammalian hosts.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"11 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713593","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}
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