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Manganese-dependent transcription regulation by MntR and PerR in Thermus thermophilus HB8. 嗜热菌 HB8 中 MntR 和 PerR 对锰的依赖性转录调控。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-06-01 Epub Date: 2024-05-12 DOI: 10.1111/mmi.15278
John K Barrows, Kamya A Stubbs, Irina F Padilla-Montoya, Thomas C Leeper, Michael W Van Dyke
{"title":"Manganese-dependent transcription regulation by MntR and PerR in Thermus thermophilus HB8.","authors":"John K Barrows, Kamya A Stubbs, Irina F Padilla-Montoya, Thomas C Leeper, Michael W Van Dyke","doi":"10.1111/mmi.15278","DOIUrl":"10.1111/mmi.15278","url":null,"abstract":"<p><p>Bacteria contain conserved mechanisms to control the intracellular levels of metal ions. Metalloregulatory transcription factors bind metal cations and play a central role in regulating gene expression of metal transporters. Often, these transcription factors regulate transcription by binding to a specific DNA sequence in the promoter region of target genes. Understanding the preferred DNA-binding sequence for transcriptional regulators can help uncover novel gene targets and provide insight into the biological role of the transcription factor in the host organism. Here, we identify consensus DNA-binding sequences and subsequent transcription regulatory networks for two metalloregulators from the ferric uptake regulator (FUR) and diphtheria toxin repressor (DtxR) superfamilies in Thermus thermophilus HB8. By homology search, we classify the DtxR homolog as a manganese-specific, MntR (TtMntR), and the FUR homolog as a peroxide-sensing, PerR (TtPerR). Both transcription factors repress separate ZIP transporter genes in vivo, and TtPerR acts as a bifunctional transcription regulator by activating the expression of ferric and hemin transport systems. We show TtPerR and TtMntR bind DNA in the presence of manganese in vitro and in vivo; however, TtPerR is unable to bind DNA in the presence of iron, likely due to iron-mediated histidine oxidation. Unlike canonical PerR homologs, TtPerR does not appear to contribute to peroxide detoxification. Instead, the TtPerR regulon and DNA binding sequence are more reminiscent of Fur or Mur homologs. Collectively, these results highlight the similarities and differences between two metalloregulatory superfamilies and underscore the interplay of manganese and iron in transcription factor regulation.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1228-1244"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912588","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
Lizards and the enzootic cycle of Borrelia burgdorferi sensu lato. 蜥蜴与博氏包虫病的流行周期。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-06-01 Epub Date: 2024-06-03 DOI: 10.1111/mmi.15271
Tristan A Nowak, Russell L Burke, Maria A Diuk-Wasser, Yi-Pin Lin
{"title":"Lizards and the enzootic cycle of Borrelia burgdorferi sensu lato.","authors":"Tristan A Nowak, Russell L Burke, Maria A Diuk-Wasser, Yi-Pin Lin","doi":"10.1111/mmi.15271","DOIUrl":"10.1111/mmi.15271","url":null,"abstract":"<p><p>Emerging and re-emerging pathogens often stem from zoonotic origins, cycling between humans and animals, and are frequently vectored and maintained by hematophagous arthropod vectors. The efficiency by which these disease agents are successfully transmitted between vertebrate hosts is influenced by many factors, including the host on which a vector feeds. The Lyme disease bacterium Borrelia burgdorferi sensu lato has adapted to survive in complex host environments, vectored by Ixodes ticks, and maintained in multiple vertebrate hosts. The versatility of Lyme borreliae in disparate host milieus is a compelling platform to investigate mechanisms dictating pathogen transmission through complex networks of vertebrates and ticks. Squamata, one of the most diverse clade of extant reptiles, is comprised primarily of lizards, many of which are readily fed upon by Ixodes ticks. Yet, lizards are one of the least studied taxa at risk of contributing to the transmission and life cycle maintenance of Lyme borreliae. In this review, we summarize the current evidence, spanning from field surveillance to laboratory infection studies, supporting their contributions to Lyme borreliae circulation. We also summarize the current understanding of divergent lizard immune responses that may explain the underlying molecular mechanisms to confer Lyme spirochete survival in vertebrate hosts. This review offers a critical perspective on potential enzootic cycles existing between lizard-tick-Borrelia interactions and highlights the importance of an eco-immunology lens for zoonotic pathogen transmission studies.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1262-1272"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238196","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}
引用次数: 0
The recombination initiation functions DprA and RecFOR suppress microindel mutations in Acinetobacter baylyi ADP1 重组起始功能 DprA 和 RecFOR 可抑制巴氏不动杆菌 ADP1 中的微吲哚突变
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-17 DOI: 10.1111/mmi.15277
Mikkel M. Liljegren, João A. Gama, Pål J. Johnsen, Klaus Harms
{"title":"The recombination initiation functions DprA and RecFOR suppress microindel mutations in Acinetobacter baylyi ADP1","authors":"Mikkel M. Liljegren, João A. Gama, Pål J. Johnsen, Klaus Harms","doi":"10.1111/mmi.15277","DOIUrl":"https://doi.org/10.1111/mmi.15277","url":null,"abstract":"Short-Patch Double Illegitimate Recombination (SPDIR) has been recently identified as a rare mutation mechanism. During SPDIR, ectopic DNA single-strands anneal with genomic DNA at microhomologies and get integrated during DNA replication, presumably acting as primers for Okazaki fragments. The resulting microindel mutations are highly variable in size and sequence. In the soil bacterium <i>Acinetobacter baylyi</i>, SPDIR is tightly controlled by genome maintenance functions including RecA. It is thought that RecA scavenges DNA single-strands and renders them unable to anneal. To further elucidate the role of RecA in this process, we investigate the roles of the upstream functions DprA, RecFOR, and RecBCD, all of which load DNA single-strands with RecA. Here we show that all three functions suppress SPDIR mutations in the wildtype to levels below the detection limit. While SPDIR mutations are slightly elevated in the absence of DprA, they are strongly increased in the absence of both DprA and RecA. This SPDIR-avoiding function of DprA is not related to its role in natural transformation. These results suggest a function for DprA in combination with RecA to avoid potentially harmful microindel mutations, and offer an explanation for the ubiquity of <i>dprA</i> in the genomes of naturally non-transformable bacteria.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954462","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
Redefining the bacteriophage mv4 site‐specific recombination system and the sequence specificity of its attB and core‐attP sites 重新定义噬菌体 mv4 位点特异性重组系统及其 attB 和核心-attP 位点的序列特异性
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-06 DOI: 10.1111/mmi.15275
Kevin Debatisse, Pierre Lopez, Maryse Poli, Philippe Rousseau, Manuel Campos, Michèle Coddeville, Muriel Cocaign‐Bousquet, Pascal Le Bourgeois
{"title":"Redefining the bacteriophage mv4 site‐specific recombination system and the sequence specificity of its attB and core‐attP sites","authors":"Kevin Debatisse, Pierre Lopez, Maryse Poli, Philippe Rousseau, Manuel Campos, Michèle Coddeville, Muriel Cocaign‐Bousquet, Pascal Le Bourgeois","doi":"10.1111/mmi.15275","DOIUrl":"https://doi.org/10.1111/mmi.15275","url":null,"abstract":"Through their involvement in the integration and excision of a large number of mobile genetic elements, such as phages and integrative and conjugative elements (ICEs), site‐specific recombination systems based on heterobivalent tyrosine recombinases play a major role in genome dynamics and evolution. However, despite hundreds of these systems having been identified in genome databases, very few have been described in detail, with none from phages that infect <jats:italic>Bacillota</jats:italic> (formerly <jats:italic>Firmicutes</jats:italic>). In this study, we reanalyzed the recombination module of <jats:italic>Lactobacillus delbrueckii</jats:italic> subsp. <jats:italic>bulgaricus</jats:italic> phage mv4, previously considered atypical compared with classical systems. Our results reveal that mv4 integrase is a 369 aa protein with all the structural hallmarks of recombinases from the Tn<jats:italic>916</jats:italic> family and that it cooperatively interacts with its recombination sites. Using randomized DNA libraries, NGS sequencing, and other molecular approaches, we show that the 21‐bp core‐<jats:italic>attP</jats:italic> and <jats:italic>attB</jats:italic> sites have structural similarities to classical systems only if considering the nucleotide degeneracy, with two 7‐bp inverted regions corresponding to <jats:sup>mv4</jats:sup>Int core‐binding sites surrounding a 7‐bp strand‐exchange region. We also examined the different compositional constraints in the core‐binding regions, which define the sequence space of permissible recombination sites.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"161 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845656","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 immune interactions of gut glycans and microbiota in health and disease 肠道糖和微生物群在健康和疾病中的免疫相互作用
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-04 DOI: 10.1111/mmi.15267
Mahmut Demirturk, Mukaddes Sena Cinar, Fikri Y. Avci
{"title":"The immune interactions of gut glycans and microbiota in health and disease","authors":"Mahmut Demirturk, Mukaddes Sena Cinar, Fikri Y. Avci","doi":"10.1111/mmi.15267","DOIUrl":"https://doi.org/10.1111/mmi.15267","url":null,"abstract":"The human digestive system harbors a vast diversity of commensal bacteria and maintains a symbiotic relationship with them. However, imbalances in the gut microbiota accompany various diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancers (CRCs), which significantly impact the well‐being of populations globally. Glycosylation of the mucus layer is a crucial factor that plays a critical role in maintaining the homeostatic environment in the gut. This review delves into how the gut microbiota, immune cells, and gut mucus layer work together to establish a balanced gut environment. Specifically, the role of glycosylation in regulating immune cell responses and mucus metabolism in this process is examined.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"85 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826239","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 binding affinity-dependent inhibition of cell growth and viability by DNA sulfur-binding domains. DNA 硫结合结构域对细胞生长和活力的抑制作用与结合亲和力有关。
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-03-13 DOI: 10.1111/mmi.15249
Yuli Wang, Fulin Ge, Jinling Liu, Wenyue Hu, Guang Liu, Zixin Deng, Xinyi He
{"title":"The binding affinity-dependent inhibition of cell growth and viability by DNA sulfur-binding domains.","authors":"Yuli Wang, Fulin Ge, Jinling Liu, Wenyue Hu, Guang Liu, Zixin Deng, Xinyi He","doi":"10.1111/mmi.15249","DOIUrl":"10.1111/mmi.15249","url":null,"abstract":"<p><p>Increasing evidence suggests that DNA phosphorothioate (PT) modification serves several purposes in the bacterial host, and some restriction enzymes specifically target PT-DNA. PT-dependent restriction enzymes (PDREs) bind PT-DNA through their DNA sulfur binding domain (SBD) with dissociation constants (K<sub>D</sub>) of 5 nM~1 μM. Here, we report that SprMcrA, a PDRE, failed to dissociate from PT-DNA after cleavage due to high binding affinity, resulting in low DNA cleavage efficiency. Expression of SBDs in Escherichia coli cells with PT modification induced a drastic loss of cell viability at 25°C when both DNA strands of a PT site were bound, with one SBD on each DNA strand. However, at this temperature, SBD binding to only one PT DNA strand elicited a severe growth lag rather than lethality. This cell growth inhibition phenotype was alleviated by raising the growth temperature. An in vitro assay mimicking DNA replication and RNA transcription demonstrated that the bound SBD hindered the synthesis of new DNA and RNA when using PT-DNA as the template. Our findings suggest that DNA modification-targeting proteins might regulate cellular processes involved in DNA metabolism in addition to being components of restriction-modification systems and epigenetic readers.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"971-983"},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120166","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
Involvement of Escherichia coli YbeX/CorC in ribosomal metabolism. 大肠杆菌 YbeX/CorC 参与核糖体代谢的情况
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-03-17 DOI: 10.1111/mmi.15248
İsmail Sarıgül, Amata Žukova, Emel Alparslan, Sille Remm, Margus Pihlak, Niilo Kaldalu, Tanel Tenson, Ülo Maiväli
{"title":"Involvement of Escherichia coli YbeX/CorC in ribosomal metabolism.","authors":"İsmail Sarıgül, Amata Žukova, Emel Alparslan, Sille Remm, Margus Pihlak, Niilo Kaldalu, Tanel Tenson, Ülo Maiväli","doi":"10.1111/mmi.15248","DOIUrl":"10.1111/mmi.15248","url":null,"abstract":"<p><p>YbeX of Escherichia coli, a member of the CorC protein family, is encoded in the same operon with ribosome-associated proteins YbeY and YbeZ. Here, we report the involvement of YbeX in ribosomal metabolism. The ΔybeX cells accumulate distinct 16S rRNA degradation intermediates in the 30S particles and the 70S ribosomes. E. coli lacking ybeX has a lengthened lag phase upon outgrowth from the stationary phase. This growth phenotype is heterogeneous at the individual cell level and especially prominent under low extracellular magnesium levels. The ΔybeX strain is sensitive to elevated growth temperatures and to several ribosome-targeting antibiotics that have in common the ability to induce the cold shock response in E. coli. Although generally milder, the phenotypes of the ΔybeX mutant overlap with those caused by ybeY deletion. A genetic screen revealed partial compensation of the ΔybeX growth phenotype by the overexpression of YbeY. These findings indicate an interconnectedness among the ybeZYX operon genes, highlighting their roles in ribosomal assembly and/or degradation.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"984-1001"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143869","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
Bacteriophage lambda site-specific recombination. 噬菌体λ位点特异性重组。
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-02-19 DOI: 10.1111/mmi.15241
Gregory D Van Duyne, Arthur Landy
{"title":"Bacteriophage lambda site-specific recombination.","authors":"Gregory D Van Duyne, Arthur Landy","doi":"10.1111/mmi.15241","DOIUrl":"10.1111/mmi.15241","url":null,"abstract":"<p><p>The site-specific recombination pathway of bacteriophage λ encompasses isoenergetic but highly directional and tightly regulated integrative and excisive reactions that integrate and excise the vial chromosome into and out of the bacterial chromosome. The reactions require 240 bp of phage DNA and 21 bp of bacterial DNA comprising 16 protein binding sites that are differentially used in each pathway by the phage-encoded Int and Xis proteins and the host-encoded integration host factor and factor for inversion stimulation proteins. Structures of higher-order protein-DNA complexes of the four-way Holliday junction recombination intermediates provided clarifying insights into the mechanisms, directionality, and regulation of these two pathways, which are tightly linked to the physiology of the bacterial host cell. Here we review our current understanding of the mechanisms responsible for regulating and executing λ site-specific recombination, with an emphasis on key studies completed over the last decade.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"895-911"},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900187","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}
引用次数: 0
In Staphylococcus aureus, the acyl-CoA synthetase MbcS supports branched-chain fatty acid synthesis from carboxylic acid and aldehyde precursors. 在金黄色葡萄球菌中,酰基-CoA 合成酶 MbcS 支持从羧酸和醛前体合成支链脂肪酸。
IF 2.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-02-16 DOI: 10.1111/mmi.15237
Marcelle C Dos Santos Ferreira, Augustus Pendleton, Won-Sik Yeo, Fabiana C Málaga Gadea, Danna Camelo, Maeve McGuire, Shaun R Brinsmade
{"title":"In Staphylococcus aureus, the acyl-CoA synthetase MbcS supports branched-chain fatty acid synthesis from carboxylic acid and aldehyde precursors.","authors":"Marcelle C Dos Santos Ferreira, Augustus Pendleton, Won-Sik Yeo, Fabiana C Málaga Gadea, Danna Camelo, Maeve McGuire, Shaun R Brinsmade","doi":"10.1111/mmi.15237","DOIUrl":"10.1111/mmi.15237","url":null,"abstract":"<p><p>In the human pathogen Staphylococcus aureus, branched-chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids. Strains deficient for BCFAs synthesis experience auxotrophy in laboratory culture and attenuated virulence during infection. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that the overexpression of SAUSA300_2542 (annotated to encode an acyl-CoA synthetase) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched-chain α-keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl-CoA synthetase activity of MbcS activates branched-chain carboxylic acids (BCCAs), and is required by S. aureus to utilize the isoleucine derivative 2-methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched-chain aldehydes into their respective BCCAs and our findings demonstrating that branched-chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous BCCAs and mediates BCFA synthesis via a de novo alternative pathway.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"865-881"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747070","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}
引用次数: 0
Histidine kinase-mediated cross-regulation of the vancomycin-resistance operon in Clostridioides difficile 组氨酸激酶介导的难辨梭状芽孢杆菌抗万古霉素操作子的交叉调节
IF 3.6 2区 生物学
Molecular Microbiology Pub Date : 2024-05-01 DOI: 10.1111/mmi.15273
Boris R. Belitsky
{"title":"Histidine kinase-mediated cross-regulation of the vancomycin-resistance operon in Clostridioides difficile","authors":"Boris R. Belitsky","doi":"10.1111/mmi.15273","DOIUrl":"https://doi.org/10.1111/mmi.15273","url":null,"abstract":"The dipeptide D-Ala-D-Ala is an essential component of peptidoglycan and the target of vancomycin. Most <i>Clostridioides difficile</i> strains possess the <i>vanG</i> operon responsible for the synthesis of D-Ala-D-Ser, which can replace D-Ala-D-Ala in peptidoglycan. The <i>C. difficile vanG</i> operon is regulated by a two-component system, VanRS, but is not induced sufficiently by vancomycin to confer resistance to this antibiotic. Surprisingly, in the absence of the VanS histidine kinase (HK), the <i>vanG</i> operon is still induced by vancomycin and also by another antibiotic, ramoplanin, in a VanR-dependent manner. This suggested the cross-regulation of VanR by another HK or kinases that are activated in the presence of certain lipid II-targeting antibiotics. We identified these HKs as CD35990 and CD22880. However, mutations in either or both HKs did not affect the regulation of the <i>vanG</i> operon in wild-type cells suggesting that intact VanS prevents the cross-activation of VanR by non-cognate HKs. Overproduction of VanR in the absence of VanS, CD35990, and CD22880 led to high expression of the <i>vanG</i> operon indicating that VanR can potentially utilize at least one more phosphate donor for its activation. Candidate targets of CD35990- and CD22880-mediated regulation in the presence of vancomycin or ramoplanin were identified by RNA-Seq.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"198 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817487","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
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