{"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":"<jats:italic>Entamoeba histolytica</jats:italic> causes invasive amoebiasis, an important neglected tropical disease with a significant global health impact. The pathogenicity and survival of <jats:italic>E. histolytica</jats:italic> and its reptilian equivalent, <jats:italic>Entamoeba invadens</jats:italic>, 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 <jats:italic>E. invadens</jats:italic> in governing cellular processes crucial for their survival, pathogenicity, and evasion of the host immune system.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"27 1","pages":""},"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}
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, <jats:italic>dltXABCD</jats:italic>, a known DAP resistance determinant, and show that LiaFSR regulates the expression of <jats:italic>sapRS</jats:italic>. 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 <jats:italic>Enterococcus faecalis</jats:italic> 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":"79 1","pages":""},"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}
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 <jats:italic>Bocaparvovirus</jats:italic> (formerly <jats:italic>Bocavirus</jats:italic>) within the <jats:italic>Parvoviridae</jats:italic> 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":"18 1","pages":""},"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}
{"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 <i>Caenorhabditis elegans</i>, 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 <i>hlh-30-</i>deficient animals. These results suggest that the microbiota of <i>C. elegans</i> 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":"114 1","pages":""},"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}
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 <i>Trypanosoma brucei</i> 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 CX<sub>9</sub>C 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":"37 1","pages":""},"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}
Ilaria Baglivo, Gaetano Malgieri, Roy Martin Roop, Ian S. Barton, Xindan Wang, Veronica Russo, Luciano Pirone, Emilia M. Pedone, Paolo V. Pedone
{"title":"MucR protein: Three decades of studies have led to the identification of a new H-NS-like protein","authors":"Ilaria Baglivo, Gaetano Malgieri, Roy Martin Roop, Ian S. Barton, Xindan Wang, Veronica Russo, Luciano Pirone, Emilia M. Pedone, Paolo V. Pedone","doi":"10.1111/mmi.15261","DOIUrl":"https://doi.org/10.1111/mmi.15261","url":null,"abstract":"MucR belongs to a large protein family whose members regulate the expression of virulence and symbiosis genes in α-proteobacteria species. This protein and its homologs were initially studied as classical transcriptional regulators mostly involved in repression of target genes by binding their promoters. Very recent studies have led to the classification of MucR as a new type of Histone-like Nucleoid Structuring (H-NS) protein. Thus this review is an effort to put together a complete and unifying story demonstrating how genetic and biochemical findings on MucR suggested that this protein is not a classical transcriptional regulator, but functions as a novel type of H-NS-like protein, which binds AT-rich regions of genomic DNA and regulates gene expression.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"33 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140553658","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}
{"title":"Physical models of bacterial chromosomes","authors":"Janni Harju, Chase P. Broedersz","doi":"10.1111/mmi.15257","DOIUrl":"https://doi.org/10.1111/mmi.15257","url":null,"abstract":"The interplay between bacterial chromosome organization and functions such as transcription and replication can be studied in increasing detail using novel experimental techniques. Interpreting the resulting quantitative data, however, can be theoretically challenging. In this minireview, we discuss how connecting experimental observations to biophysical theory and modeling can give rise to new insights on bacterial chromosome organization. We consider three flavors of models of increasing complexity: simple polymer models that explore how physical constraints, such as confinement or plectoneme branching, can affect bacterial chromosome organization; bottom‐up mechanistic models that connect these constraints to their underlying causes, for instance, chromosome compaction to macromolecular crowding, or supercoiling to transcription; and finally, data‐driven methods for inferring interpretable and quantitative models directly from complex experimental data. Using recent examples, we discuss how biophysical models can both deepen our understanding of how bacterial chromosomes are structured and give rise to novel predictions about bacterial chromosome organization.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"20 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140352198","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}
Annina Bindschedler, Jacqueline Schmuckli-Maurer, Sophie Buchser, Tara D. Fischer, Rahel Wacker, Tim Davalan, Jessica Brunner, Volker T. Heussler
{"title":"LC3B labeling of the parasitophorous vacuole membrane of Plasmodium berghei liver stage parasites depends on the V-ATPase and ATG16L1","authors":"Annina Bindschedler, Jacqueline Schmuckli-Maurer, Sophie Buchser, Tara D. Fischer, Rahel Wacker, Tim Davalan, Jessica Brunner, Volker T. Heussler","doi":"10.1111/mmi.15259","DOIUrl":"https://doi.org/10.1111/mmi.15259","url":null,"abstract":"The protozoan parasite <i>Plasmodium</i>, the causative agent of malaria, undergoes an obligatory stage of intra-hepatic development before initiating a blood-stage infection. Productive invasion of hepatocytes involves the formation of a parasitophorous vacuole (PV) generated by the invagination of the host cell plasma membrane. Surrounded by the PV membrane (PVM), the parasite undergoes extensive replication. During intracellular development in the hepatocyte, the parasites provoke the <i>Plasmodium</i>-associated autophagy-related (PAAR) response. This is characterized by a long-lasting association of the autophagy marker protein, and ATG8 family member, LC3B with the PVM. LC3B localization at the PVM does not follow the canonical autophagy pathway since upstream events specific to canonical autophagy are dispensable. Here, we describe that LC3B localization at the PVM of <i>Plasmodium</i> parasites requires the V-ATPase and its interaction with ATG16L1. The WD40 domain of ATG16L1 is crucial for its recruitment to the PVM. Thus, we provide new mechanistic insight into the previously described PAAR response targeting <i>Plasmodium</i> liver stage parasites.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"256 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140346497","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}
{"title":"The Lrs14 family of DNA-binding proteins as nucleoid-associated proteins in the Crenarchaeal order Sulfolobales","authors":"Veerke De Kock, Eveline Peeters, Rani Baes","doi":"10.1111/mmi.15260","DOIUrl":"https://doi.org/10.1111/mmi.15260","url":null,"abstract":"Organization of archaeal chromatin combines bacterial, eukaryotic, and unique characteristics. Many archaeal lineages harbor a wide diversity of small and highly expressed nucleoid-associated proteins, which are involved in DNA structuring. In Sulfolobales, representing model organisms within the Crenarchaeota, Sul7d, Cren7, Sul10a, and Sul12a are well-characterized nucleoid-associated proteins. Here, we combine evidence that the Lrs14 family of DNA binders is part of the repertoire of nucleoid-associated proteins in Sulfolobales. Lrs14-encoding genes are widespread within genomes of different members of the Sulfolobales, typically encoded as four to nine homologs per genome. The Lrs14 proteins harbor a winged helix-turn-helix DNA-binding domain and are typified by a coiled–coil dimerization. They are characterized by distinct sequence- and structure-based features, including redox-sensitive motifs and residues targeted for posttranslational modification, allowing a further classification of the family into five conserved clusters. Lrs14-like proteins have unique DNA-organizing properties. By binding to the DNA nonsequence specifically and in a highly cooperative manner, with a slight preference for AT-rich promoter regions, they introduce DNA kinks and are able to affect transcription of adjacent transcription units either positively or negatively. Genes encoding Lrs14-type proteins display considerable differential expression themselves in response to various stress conditions, with certain homologs being specific to a particular stressor. Taken together, we postulate that members of the Lrs14 family can be considered nucleoid-associated proteins in Sulfolobales, combining a DNA-structuring role with a global gene expression role in response to stress conditions.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"4 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343323","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}
{"title":"Whole-genome CRISPR screens to understand Apicomplexan-host interactions.","authors":"Eva Hesping, Justin A Boddey","doi":"10.1111/mmi.15221","DOIUrl":"10.1111/mmi.15221","url":null,"abstract":"<p><p>Apicomplexan parasites are aetiological agents of numerous diseases in humans and livestock. Functional genomics studies in these parasites enable the identification of biological mechanisms and protein functions that can be targeted for therapeutic intervention. Recent improvements in forward genetics and whole-genome screens utilising CRISPR/Cas technology have revolutionised the functional analysis of genes during Apicomplexan infection of host cells. Here, we highlight key discoveries from CRISPR/Cas9 screens in Apicomplexa or their infected host cells and discuss remaining challenges to maximise this technology that may help answer fundamental questions about parasite-host interactions.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"717-726"},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472495","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}