Molecular Microbiology最新文献_第8页

Borrelia burgdorferi PlzA is a cyclic-di-GMP dependent DNA and RNA binding protein. Borrelia burgdorferi PlzA 是一种依赖环二-GMP 的 DNA 和 RNA 结合蛋白。

IF 2.6 2区生物学

Molecular Microbiology Pub Date : 2024-05-01 Epub Date: 2024-03-25 DOI: 10.1111/mmi.15254

Nerina Jusufovic, Andrew C Krusenstjerna, Christina R Savage, Timothy C Saylor, Catherine A Brissette, Wolfram R Zückert, Paula J Schlax, Md A Motaleb, Brian Stevenson

{"title":"Borrelia burgdorferi PlzA is a cyclic-di-GMP dependent DNA and RNA binding protein.","authors":"Nerina Jusufovic, Andrew C Krusenstjerna, Christina R Savage, Timothy C Saylor, Catherine A Brissette, Wolfram R Zückert, Paula J Schlax, Md A Motaleb, Brian Stevenson","doi":"10.1111/mmi.15254","DOIUrl":"10.1111/mmi.15254","url":null,"abstract":"The PilZ domain-containing protein, PlzA, is the only known cyclic di-GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here, we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of binding c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the major groove of DNA and that sequence length and G-C content play a role in DNA binding affinity. PlzA is a dual-domain protein with a PilZ-like N-terminal domain linked to a canonical C-terminal PilZ domain. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids independently of c-di-GMP. The C-terminal domain, which includes the c-di-GMP binding motifs, did not bind nucleic acids under any tested conditions. Our data are supported by computational docking, which predicts that c-di-GMP binding at the C-terminal domain stabilizes the overall protein structure and facilitates PlzA-DNA interactions via residues in the N-terminal domain. Based on our data, we propose that levels of c-di-GMP during the various stages of the enzootic life cycle direct PlzA binding to regulatory targets.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288522","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

Identification of a 1-acyl-glycerol-3-phosphate acyltransferase from Mycobacterium tuberculosis, a key enzyme involved in triacylglycerol biosynthesis 鉴定结核分枝杆菌中的 1-酰基-甘油-3-磷酸酰基转移酶--一种参与三酰甘油生物合成的关键酶

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-26 DOI: 10.1111/mmi.15265

Meghna Santoshi, Harsh Bansia, Muzammil Hussain, Abodh Kumar Jha, Valakunja Nagaraja

{"title":"Identification of a 1-acyl-glycerol-3-phosphate acyltransferase from Mycobacterium tuberculosis, a key enzyme involved in triacylglycerol biosynthesis","authors":"Meghna Santoshi, Harsh Bansia, Muzammil Hussain, Abodh Kumar Jha, Valakunja Nagaraja","doi":"10.1111/mmi.15265","DOIUrl":"https://doi.org/10.1111/mmi.15265","url":null,"abstract":"Latent tuberculosis, caused by dormant Mycobacterium tuberculosis (Mtb), poses a threat to global health through the incubation of undiagnosed infections within the community. Dormant Mtb, which is phenotypically tolerant to antibiotics, accumulates triacylglycerol (TAG) utilizing fatty acids obtained from macrophage lipid droplets. TAG is vital to mycobacteria, serving as a cell envelope component and energy reservoir during latency. TAG synthesis occurs by sequential acylation of glycerol-3-phosphate, wherein the second acylation step is catalyzed by acylglycerol-3-phosphate acyltransferase (AGPAT), resulting in the production of phosphatidic acid (PA), a precursor for the synthesis of TAG and various phospholipids. Here, we have characterized a putative acyltransferase of Mtb encoded by Rv3816c. We found that Rv3816c has all four characteristic motifs of AGPAT, exists as a membrane-bound enzyme, and functions as 1-acylglycerol-3-phosphate acyltransferase. The enzyme could transfer the acyl group to acylglycerol-3-phosphate (LPA) from monounsaturated fatty acyl-coenzyme A of chain length 16 or 18 to produce PA. Complementation of Escherichia coli PlsC mutant in vivo by Rv3816c confirmed that it functions as AGPAT. Its active site mutants, H43A and D48A, were incapable of transferring the acyl group to LPA in vitro and were not able to rescue the growth defect of E. coli PlsC mutant in vivo. Identifying Rv3816c as AGPAT and comparing its properties with other AGPAT homologs is not only a step toward understanding the TAG biosynthesis in mycobacteria but has the potential to explore it as a drug target.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651800","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

House of CarDs: Functional insights into the transcriptional regulator CdnL CarDs 之家：转录调节因子 CdnL 的功能研究

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-25 DOI: 10.1111/mmi.15268

Erika L. Smith, Erin D. Goley

引用次数: 0

Ancestral TALE homeobox protein transcription factor regulates actin dynamics and cellular activities of protozoan parasite Entamoeba invadens 祖先 TALE 同源盒蛋白转录因子调控原生动物寄生虫 Entamoeba invadens 的肌动蛋白动力学和细胞活动

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-24 DOI: 10.1111/mmi.15266

Meenakshi Pandey, Shilpa Sarkar, Sudip K. Ghosh

{"title":"Ancestral TALE homeobox protein transcription factor regulates actin dynamics and cellular activities of protozoan parasite Entamoeba invadens","authors":"Meenakshi Pandey, Shilpa Sarkar, Sudip K. Ghosh","doi":"10.1111/mmi.15266","DOIUrl":"https://doi.org/10.1111/mmi.15266","url":null,"abstract":"Entamoeba histolytica causes invasive amoebiasis, an important neglected tropical disease with a significant global health impact. The pathogenicity and survival of E. histolytica and its reptilian equivalent, Entamoeba invadens, relies on its ability to exhibit efficient motility, evade host immune responses, and exploit host resources, all of which are governed by the actin cytoskeleton remodeling. Our study demonstrates the early origin and the regulatory role of TALE homeobox protein EiHbox1 in actin‐related cellular processes. Several genes involved in different biological pathways, including actin dynamics are differentially expressed in EiHbox1 silenced cells. EiHbox1 silenced parasites showed disrupted F‐actin organization and loss of cellular polarity. EiHbox1's presence in the anterior region of migrating cells further suggests its involvement in maintaining cellular polarity. Loss of polarized morphology of EiHbox1 silenced parasites leads to altered motility from fast, directionally persistent, and highly chemotactic to slow, random, and less chemotactic, which subsequently leads to defective aggregation during encystation. EiHbox1 knockdown also resulted in a significant reduction in phagocytic capacity and poor capping response. These findings highlight the importance of EiHbox1 of E. invadens in governing cellular processes crucial for their survival, pathogenicity, and evasion of the host immune system.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642513","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

Regulatory interactions between daptomycin‐ and bacitracin‐responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis 达托霉素和杆菌肽反应途径之间的调控相互作用协调了粪肠球菌的细胞膜抗生素耐药性反应

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-22 DOI: 10.1111/mmi.15264

Sali M. Morris, Laura Wiens, Olivia Rose, Georg Fritz, Tim Rogers, Susanne Gebhard

{"title":"Regulatory interactions between daptomycin‐ and bacitracin‐responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis","authors":"Sali M. Morris, Laura Wiens, Olivia Rose, Georg Fritz, Tim Rogers, Susanne Gebhard","doi":"10.1111/mmi.15264","DOIUrl":"https://doi.org/10.1111/mmi.15264","url":null,"abstract":"Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope‐acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two‐component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP‐resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS‐target genes under dual control, where expression is directly controlled by SapRS, which itself is up‐regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636451","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

Chaperones Hsc70 and Hsp70 play distinct roles in the replication of bocaparvovirus minute virus of canines 伴侣蛋白 Hsc70 和 Hsp70 在犬细小病毒复制过程中发挥不同作用

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-17 DOI: 10.1111/mmi.15263

Jianhui Guo, Yan Yan, Jinhan Sun, Kai Ji, Zhiping Hei, Liang Zeng, Huanzhou Xu, Xiang Ren, Yuning Sun

{"title":"Chaperones Hsc70 and Hsp70 play distinct roles in the replication of bocaparvovirus minute virus of canines","authors":"Jianhui Guo, Yan Yan, Jinhan Sun, Kai Ji, Zhiping Hei, Liang Zeng, Huanzhou Xu, Xiang Ren, Yuning Sun","doi":"10.1111/mmi.15263","DOIUrl":"https://doi.org/10.1111/mmi.15263","url":null,"abstract":"Minute virus of canines (MVC) belongs to the genus Bocaparvovirus (formerly Bocavirus) within the Parvoviridae family and causes serious respiratory and gastrointestinal symptoms in neonatal canines worldwide. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. However, little is known about the MVC‐host cell interactions. In this study, we identified that two cellular proteins (Hsc70 and Hsp70) interacted with NS1 and VP2 proteins of MVC, and both two domains of Hsc70/Hsp70 were mediated for their interactions. Functional studies revealed that Hsp70 was induced by MVC infection, knockdown of Hsc70 considerably suppressed MVC replication, whereas the replication was dramatically promoted by Hsp70 knockdown. It is interesting that low amounts of overexpressed Hsp70 enhanced viral protein expression and virus production, but high amounts of Hsp70 overexpression weakened them. Upon Hsp70 overexpressing, we observed that the ubiquitination of viral proteins changed with Hsp70 overexpression, and proteasome inhibitor (MG132) restored an accumulation of viral proteins. In addition, we verified that Hsp70 family inhibitors remarkably decreased MVC replication. Overall, we identified Hsc70 and Hsp70 as interactors of MVC NS1 and VP2 proteins and were involved in MVC replication, which may provide novel targets for anti‐MVC approach.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140607944","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

Distinct members of the Caenorhabditis elegans CeMbio reference microbiota exert cryptic virulence that is masked by host defense 草履虫 CeMbio 参考微生物群的不同成员具有被宿主防御所掩盖的隐性毒力

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-16 DOI: 10.1111/mmi.15258

Xavier Gonzalez, Javier E. Irazoqui

{"title":"Distinct members of the Caenorhabditis elegans CeMbio reference microbiota exert cryptic virulence that is masked by host defense","authors":"Xavier Gonzalez, Javier E. Irazoqui","doi":"10.1111/mmi.15258","DOIUrl":"https://doi.org/10.1111/mmi.15258","url":null,"abstract":"Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. Understanding the ability of each distinct community member to promote or impair host health, alone or in the context of the community, is imperative for understanding how differences in community structure affect host health and vice versa. Recently, a reference 12-member microbiota for the model organism Caenorhabditis elegans, known as CeMbio, was defined. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh-WNT, and HLH-30/TFEB pathways. Although distinct CeMbio members differed in their ability to activate the PMK-1/p38 pathway, the ability to do so did not correlate with bacterial-induced lifespan reduction in wild-type or immunodeficient animals. In contrast, most species activated HLH-30/TFEB and showed virulence toward hlh-30-deficient animals. These results suggest that the microbiota of C. elegans is rife with bacteria that can shorten the host's lifespan if host defense is compromised and that HLH-30/TFEB is a fundamental and key host protective factor.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556767","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

Intermembrane space-localized TbTim15 is an essential subunit of the single mitochondrial inner membrane protein translocase of trypanosomes 膜间空间定位的 TbTim15 是锥虫单线粒体内膜蛋白质转运酶的一个重要亚基

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-15 DOI: 10.1111/mmi.15262

Corinne von Känel, Silke Oeljeklaus, Christoph Wenger, Philip Stettler, Anke Harsman, Bettina Warscheid, André Schneider

{"title":"Intermembrane space-localized TbTim15 is an essential subunit of the single mitochondrial inner membrane protein translocase of trypanosomes","authors":"Corinne von Känel, Silke Oeljeklaus, Christoph Wenger, Philip Stettler, Anke Harsman, Bettina Warscheid, André Schneider","doi":"10.1111/mmi.15262","DOIUrl":"https://doi.org/10.1111/mmi.15262","url":null,"abstract":"All mitochondria import >95% of their proteins from the cytosol. This process is mediated by protein translocases in the mitochondrial membranes, whose subunits are generally highly conserved. Most eukaryotes have two inner membrane protein translocases (TIMs) that are specialized to import either presequence-containing or mitochondrial carrier proteins. In contrast, the parasitic protozoan Trypanosoma brucei has a single TIM complex consisting of one conserved and five unique subunits. Here, we identify candidates for new subunits of the TIM or the presequence translocase-associated motor (PAM) using a protein–protein interaction network of previously characterized TIM and PAM subunits. This analysis reveals that the trypanosomal TIM complex contains an additional trypanosomatid-specific subunit, designated TbTim15. TbTim15 is associated with the TIM complex, lacks transmembrane domains, and localizes to the intermembrane space. TbTim15 is essential for procyclic and bloodstream forms of trypanosomes. It contains two twin CX9C motifs and mediates import of both presequence-containing and mitochondrial carrier proteins. While the precise function of TbTim15 in mitochondrial protein import is unknown, our results are consistent with the notion that it may function as an import receptor for the non-canonical trypanosomal TIM complex.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556932","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

MucR protein: Three decades of studies have led to the identification of a new H-NS-like protein MucR 蛋白：三十年的研究发现了一种新的 H-NS 类蛋白

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-15 DOI: 10.1111/mmi.15261

Ilaria Baglivo, Gaetano Malgieri, Roy Martin Roop, Ian S. Barton, Xindan Wang, Veronica Russo, Luciano Pirone, Emilia M. Pedone, Paolo V. Pedone

引用次数: 0

Physical models of bacterial chromosomes 细菌染色体的物理模型

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2024-04-05 DOI: 10.1111/mmi.15257

Janni Harju, Chase P. Broedersz

引用次数: 0