Molecular Microbiology最新文献

{"title":"Comparative Transcriptomic Analysis of Human Macrophages During Mycobacterium avium Versus Mycobacterium tuberculosis Infection","authors":"Gül Kilinç, Robin H. G. A. van den Biggelaar, Tom H. M. Ottenhoff, Leon H. Mei, Anno Saris","doi":"10.1111/mmi.70045","DOIUrl":"https://doi.org/10.1111/mmi.70045","url":null,"abstract":"The treatment of <jats:styled-content style=\"fixed-case\"> <jats:italic>Mycobacterium avium</jats:italic> </jats:styled-content> ( <jats:italic>Mav</jats:italic> ) infection, responsible for over 80% of nontuberculous mycobacterial pulmonary disease, remains challenging due to rising antibiotic resistance and unsatisfactory success rates. Hence, there is a need for a deeper understanding of host–pathogen interactions to inform the development of alternative therapeutic approaches, like host‐directed therapy (HDT), aimed at improving host antimycobacterial defenses. However, compared to <jats:styled-content style=\"fixed-case\"> <jats:italic>Mycobacterium tuberculosis</jats:italic> </jats:styled-content> ( <jats:italic>Mtb</jats:italic> ) infections, knowledge of host–pathogen interactions for <jats:italic>Mav</jats:italic> infection is still limited. To address this knowledge gap, we performed a genome‐wide host transcriptomic analysis of <jats:italic>Mav</jats:italic> ‐infected primary human macrophages—the primary host cell—alongside <jats:italic>Mtb</jats:italic> ‐infected macrophages to leverage insights from <jats:italic>Mtb</jats:italic> research. Our findings show substantial overlap in the gene expression patterns between <jats:italic>Mav</jats:italic> ‐infected and <jats:italic>Mtb</jats:italic> ‐infected macrophages, including induction of cytokine responses and modulation of various G‐protein coupled receptors (GPCRs) involved in (lipid‐mediated) macrophage immune functions. Notable differences were observed in the expression of immediate early genes (IEGs), phospholipases, and genes of the GTPase of immunity‐associated protein (GIMAP) family. This study laid a foundation for identifying both shared and <jats:italic>Mav</jats:italic> ‐specific host response pathways, providing direction for future investigations into host–pathogen interactions during <jats:italic>Mav</jats:italic> infection and the identification of novel targets for HDT.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"22 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903604","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 Mannose Phosphotransferase System in Enterococcus lactis Is Essential for Gastrointestinal Colonization","authors":"Linan Xu, Xiangpeng Yang, Xingshuai Li, Yufan Liu, Jia Yin, Gaoyuan Dong, Chenyan Li, Weishi Ni, Shanpeng Zhang, Bin Ye, Junfei Ma, Xinglin Zhang","doi":"10.1111/mmi.70040","DOIUrl":"https://doi.org/10.1111/mmi.70040","url":null,"abstract":"<jats:italic>Enterococcus lactis</jats:italic> , a recently established species that was previously classified as <jats:styled-content style=\"fixed-case\"> <jats:italic>Enterococcus faecium</jats:italic> </jats:styled-content> clade B, is a common commensal in human and animal intestines. Unlike the opportunistic pathogen <jats:styled-content style=\"fixed-case\"> <jats:italic>E. faecium</jats:italic> </jats:styled-content> , it is largely harmless and rarely associated with clinical infections. Given its recent taxonomic classification, studies on this bacterium are scarce, and the key mechanisms that facilitate its intestinal colonization remain particularly elusive. The capability to utilize different sugars is an important factor in colonizing different ecological niches, particularly in the Gastrointestinal (GI) tract, where carbohydrates are fiercely competed for by a large number of microbes. In this study, we characterized an <jats:italic> <jats:styled-content style=\"fixed-case\">E. lactis</jats:styled-content> pts </jats:italic> gene cluster that is highly conserved in <jats:styled-content style=\"fixed-case\"> <jats:italic>E. lactis</jats:italic> </jats:styled-content> and <jats:styled-content style=\"fixed-case\"> <jats:italic>E. faecium</jats:italic> </jats:styled-content> , and is widely present in numerous other bacterial species. Two gene‐deletion mutants of the putative <jats:italic>pts</jats:italic> gene cluster exhibited markedly reduced growth on mannose and failed to colonize the GI tract of mice. These results demonstrate the crucial role of the mannose‐utilization PTS in the intestinal colonization of <jats:styled-content style=\"fixed-case\"> <jats:italic>E. lactis</jats:italic> </jats:styled-content> , providing new insight into the carbohydrate‐driven colonization mechanisms of gut microbes.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"29 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807840","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 FsrA ‐Mediated Iron‐Sparing Response Regulates the Biosynthesis of the Epipeptide EPE in Bacillus subtilis","authors":"Sarah Miercke, Rabea Ghandour, Kai Papenfort, Thorsten Mascher","doi":"10.1111/mmi.70039","DOIUrl":"https://doi.org/10.1111/mmi.70039","url":null,"abstract":"Under severe nutrient‐limiting conditions, <jats:styled-content style=\"fixed-case\"> <jats:italic>Bacillus subtilis</jats:italic> </jats:styled-content> is able to form highly resilient endospores for survival. However, to avoid this irreversible process, it employs an adaptive strategy termed cannibalism, a form of programmed cell death, to outcompete siblings and delay sporulation. One of the three cannibalism toxins, the epipeptide EPE, is encoded by the <jats:italic>epeXEPAB</jats:italic> operon. The pre‐pro‐peptide EpeX undergoes post‐translational modification and processing to be secreted as the mature EPE toxin. While EPE production is tightly regulated at multiple levels, this study focuses on the post‐transcriptional control by the small regulatory RNA FsrA, which is transcriptionally regulated by the global iron response regulator Fur. Electrophoretic mobility shift assays and RNA structure probing revealed two binding sites of FsrA within the intergenic region between <jats:italic>epeX</jats:italic> and <jats:italic>epeE</jats:italic> flanking the annotated <jats:italic>epeX</jats:italic> terminator structure and potentially interfering with RNA stability and <jats:italic>epeXEP</jats:italic> expression. Reporter assays revealed decreased levels of EPE‐dependent stress response in the absence of FsrA, indicative of a positive FsrA effect on gene expression under iron‐limited conditions; in contrast to the normally inhibitory activity of FsrA. Together, our findings suggest that under iron starvation, FsrA promotes RNA processing and enables <jats:italic>epeE</jats:italic> translation, ultimately enhancing EPE production.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"23 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770678","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 Gfr Uptake System Provides a Context-Dependent Fitness Advantage to Salmonella Typhimurium SL1344 During the Initial Gut Colonization Phase.","authors":"Lea Fuchs, Cora Lisbeth Dieterich, Elena Melgarejo Ros, Philipp Keller, Anna Sintsova, Leanid Laganenka, Thomas A Scott, Christopher Schubert, Shinichi Sunagawa, Julia A Vorholt, Jörn Piel, Wolf-Dietrich Hardt, Bidong D Nguyen","doi":"10.1111/mmi.70027","DOIUrl":"10.1111/mmi.70027","url":null,"abstract":"<p><p>Salmonella enterica serovar Typhimurium (S. Tm) is a major cause of foodborne diarrhea. However, in healthy individuals, the microbiota typically restricts the growth of incoming pathogens, a protective mechanism termed colonization resistance (CR). To circumvent CR, Salmonella strains can utilize private nutrients that remain untapped by the resident microbiota. However, the metabolic pathways and environmental niches promoting pathogen growth are still not completely understood. Here, we investigate the significance of the gfr operon in gut colonization of S. Tm, which is essential for the utilization of fructoselysine (FL) and glucoselysine (GL). These Amadori compounds are present in heated foods with high protein and carbohydrate contents. We detected FL in both mouse chow and the intestinal tract of mice and showed that gfr mutants are attenuated during the initial phase of colonization in the murine model. Experiments in gnotobiotic mice and competition experiments with Escherichia coli suggest that gfr-dependent fitness advantage is context-dependent. We conclude that dietary Amadori products like FL can support S. Tm gut colonization, depending on the metabolic capacities of the microbiota.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"507-520"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12675984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280875","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}

{"title":"The Dual Role of the 16mer Motif Within the 3′ Untranslated Region of the Variant Surface Glycoprotein of Trypanosoma brucei","authors":"Majeed Bakari-Soale, Christopher Batram, Henriette Zimmermann, Nicola G. Jones, Markus Engstler","doi":"10.1111/mmi.70031","DOIUrl":"https://doi.org/10.1111/mmi.70031","url":null,"abstract":"The variant surface glycoprotein (VSG) of African trypanosomes is essential for the survival of bloodstream form parasites. These parasites undergo antigenic variation, an immune evasion strategy in which they periodically switch VSG expression from one isoform to another. The molecular processes central to the expression and regulation of the VSG are however not fully understood. In general, the regulation of gene expression in trypanosomes is largely post-transcriptional. Regulatory sequences, mostly present in the 3′ UTRs, often serve as key elements in the modulation of the levels of individual mRNAs. In <i>T. brucei</i> VSG genes, a 16mer motif within the 3′ UTR has been shown to be essential for the stability of <i>VSG</i> transcripts and abundant VSG expression. This motif is 100% conserved in the 3′ UTRs of all transcribed and non-transcribed VSG genes. As a stability-associated sequence element, the absence of nucleotide substitutions in the 16mer is however exceptional. We therefore hypothesised that the motif is involved in other essential roles/processes besides the stability of the <i>VSG</i> transcripts. In this study, we demonstrate that the 100% conservation of the 16mer motif is not essential for cell viability or for the maintenance of functional VSG protein levels. We further show that the intact motif in the active VSG 3′ UTR is neither required to promote VSG silencing during switching nor is it needed during differentiation from bloodstream forms to procyclic forms. Ectopic overexpression of a second VSG, however, requires the intact 16mer motif within the ectopic VSG 3′ UTR to trigger silencing and exchange of the active VSG, suggesting a role for the motif in transcriptional VSG switching. The enigmatic 16mer motif therefore appears to play a dual role in transcriptional <i>VSG</i> switching and <i>VSG</i> transcript stability.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531477","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":"DNA Binding by BosR Controls RpoS ‐Dependent and ‐Independent Gene Expression in Borrelia burgdorferi","authors":"André A. Grassmann, Melissa A. McLain, Michael R. Freeman, Melissa J. Caimano, Justin D. Radolf","doi":"10.1111/mmi.70036","DOIUrl":"https://doi.org/10.1111/mmi.70036","url":null,"abstract":"BosR, the sole member of the ferric uptake regulator (FUR) family in <jats:styled-content style=\"fixed-case\"> <jats:italic>Borrelia burgdorferi</jats:italic> </jats:styled-content> , is essential for the spirochete's transcriptional adaptation to the mammalian host environment. Although best known for activating <jats:italic>rpoS</jats:italic> and establishing the mammalian‐phase RpoS regulon, BosR originally was linked to regulation of genes involved in <jats:italic>B. burgdorferi</jats:italic> 's oxidative stress response. Here, we show that BosR governs gene expression through both RpoS‐dependent and RpoS‐independent mechanisms under in vitro and mammalian host‐adapted conditions. Using RNA‐seq and a DNA‐binding‐defective BosR‐R39A mutant, we demonstrate that DNA binding is essential for BosR's global regulatory functions. BosR activates <jats:italic>rpoS</jats:italic> , promotes RpoS‐dependent gene regulation, and independently modulates a distinct set of genes involved in a variety of cellular functions, including genome maintenance, chemotaxis, and virulence. Notably, canonical oxidative stress response genes previously attributed to BosR were not differentially expressed in Δ <jats:italic>bosR</jats:italic> strains in vitro or in mammals. Despite its broad regulatory scope, BosR does not recognize a single, conserved DNA‐binding motif, suggesting that DNA occupancy is influenced by local sequence context or DNA topology. Our findings support a bifunctional model in which BosR collaborates with RNA polymerase (RNAP)‐RpoS holoenzyme to activate and repress RpoS‐regulated genes, while functioning in a FUR‐like manner to control RpoD‐dependent genes independently of RNAP interaction.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"174 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515541","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":"When One Is Enough: The Only Gα Subunit Governs Encystation and Other Cellular Processes in Entamoeba invadens","authors":"Shilpa Sarkar, Tiasha Chakraborty, Sudip K. Ghosh","doi":"10.1111/mmi.70035","DOIUrl":"https://doi.org/10.1111/mmi.70035","url":null,"abstract":"Gα, Gβ, and Gγ—the heterotrimeric G protein subunits transmit signals from G-protein coupled receptors (GPCRs) to downstream pathways. The causative agent of Amoebiasis, <i>Entamoeba</i>, has been presumed to contain a GPCR signaling pathway playing a role in its encystation, phagocytosis, and motility. A Gα subunit, EhGα1, has been characterized earlier in <i>Entamoeba histolytica</i> , which is involved in its different pathogenic processes. Here, we have characterized its ortholog, EiGα1, in the reptilian model, <i>Entamoeba invadens</i> , which expresses both in trophozoites and during encystation. Silencing EiGα1 through trigger-mediated knockdown reduces efficiency and leads to improper cell aggregation and abnormal chitin wall formation during encystation. Downregulation of EiGα1 results in anomalous F-actin polymerization. EiGα1 silenced cells also exhibit loss of polarity and reduced motility. Furthermore, EiGα1 knockdown also results in decreased phagocytosis of bacteria. Our findings indicate that EiGα1 controls the expression of two vital proteins in <i>Entamoeba</i>—the atypical EiMAPK15 and the homeobox transcription factor EiHbox1—which modulates cyst-wall development and actin reorganization. In conclusion, our findings provide strong evidence for a GPCR signaling network in <i>Entamoeba</i> and highlight the essential function of the Gα subunit in stage conversion and actin cytoskeleton rearrangement.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145478138","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":"Identification of an ERGIC ‐Like Compartment in Fission Yeast: Emp43 Functions as a Lectin‐Like Cargo Receptor for Glycosylated Proteins","authors":"Iori Imamura, Soma Kawaguchi, Shotaro Suzuki, Yuki Kamiya, Yuzuna Ohnishi, Juri Ueda, Kento Nashiki, Kaoru Takegawa, Mitsuaki Tabuchi, Naotaka Tanaka","doi":"10.1111/mmi.70033","DOIUrl":"https://doi.org/10.1111/mmi.70033","url":null,"abstract":"The endoplasmic reticulum‐Golgi intermediate compartment (ERGIC) plays a crucial role in the secretory pathway; however, its existence and function in lower eukaryotes remain largely unexamined. In this study, we identified Emp43 (SPBC4F6.05c) of <jats:italic>Schizosaccharomyces pombe</jats:italic> , an orthologue of human ( <jats:styled-content style=\"fixed-case\"> <jats:italic>Homo sapiens</jats:italic> </jats:styled-content> ) ERGIC‐53, and demonstrated its localization to an ERGIC‐like compartment. The localization of Emp43 depended on its C‐terminal KYL motif and oligomerization through the CC1 domain. Deletion of <jats:italic>S. pombe emp43</jats:italic> <jats:sup>+</jats:sup> resulted in significant sensitivity to MgCl <jats:sub>2</jats:sub> and FK506, along with defects in septum integrity, indicating a role in cell wall maintenance. Further analysis identified Ssp120 of <jats:italic>S. pombe</jats:italic> , an orthologue of human MCFD2, as a functional partner of Emp43. Yeast two‐hybrid assays confirmed a strong interaction between Emp43 and Ssp120, and both proteins co‐localized within an ERGIC‐like compartment. Additionally, we identified Meu17 of <jats:italic>S. pombe</jats:italic> , a glucan‐α‐1,4‐glucosidase homolog, as a potential ligand for Emp43. Overexpression of Meu17 rescued MgCl <jats:sub>2</jats:sub> sensitivity in both <jats:italic>emp43</jats:italic> Δ and <jats:italic>ssp120</jats:italic> Δ strains, while mutations in its N‐linked glycosylation sites (N383, N409) or its predicted active site (D203) disrupted its septum localization and functional rescue capability. Our findings indicate that Emp43 forms a complex with Ssp120 to facilitate the transport of glycosylated proteins, such as Meu17, within an ERGIC‐like compartment in fission yeast <jats:italic>S. pombe</jats:italic> . This study provides the first evidence of an ERGIC‐like structure in <jats:italic>S. pombe</jats:italic> and highlights the conserved nature of ERGIC‐associated mechanisms across eukaryotes.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"107 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461942","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":"How Pathogens Maintain Proteostasis During Infection.","authors":"Carissa Chan,Eduardo A Groisman","doi":"10.1111/mmi.70034","DOIUrl":"https://doi.org/10.1111/mmi.70034","url":null,"abstract":"Molecular chaperones play a critical role in proteostasis by aiding the folding of newly synthesized proteins and the refolding of misfolded proteins. Cells must match the protein synthesis rate to the protein folding capacity to avoid the accumulation of unfolded proteins that can form toxic aggregates. The Hsp70 chaperone DnaK binds to ribosomes and decreases protein synthesis in the bacterial pathogen Salmonella enterica serovar Typhimurium when facing cytoplasmic Mg2+ starvation, an infection-relevant stress that disrupts proteostasis. DnaK decreases protein synthesis independently of J-domain cochaperones and nucleotide exchange factor GrpE even though J-domain cochaperones and GrpE are required for DnaK's canonical role in protein folding and refolding. DnaK's activity contrasts with that exhibited by the bacteria-specific chaperone trigger factor, which associates with ribosomes and carries out cotranslational protein folding in Mg2+-abundant conditions. Under infection-relevant conditions, the master regulator of S. typhimurium virulence and Mg2+ homeostasis PhoP promotes the expression of DnaK, but not of J-domain cochaperones, GrpE, or trigger factor, suggesting that the differential expression of chaperones and cochaperones furthers S. typhimurium pathogenesis. Hsp70 chaperones also associate with ribosomes in eukaryotic cells but instead promote protein synthesis, the opposite effect that DnaK binding to ribosomes has in bacteria. Thus, Hsp70 chaperone activity differs across growth conditions and among organisms.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"53 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433766","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":"Candida albicans Cells Lacking AP ‐2 Have Defective Hyphae and Are Avirulent Despite Increased Host Uptake and Intracellular Proliferation in Macrophages","authors":"Stella Christou, Shannon Evans, Harriet Knafler, Iwona Smaczynska‐de Rooij, Kathryn R. Ayscough, Simon A. Johnston","doi":"10.1111/mmi.70032","DOIUrl":"https://doi.org/10.1111/mmi.70032","url":null,"abstract":"<jats:styled-content style=\"fixed-case\"> <jats:italic>Candida albicans</jats:italic> </jats:styled-content> is a commensal microbe and opportunistic human pathogen. <jats:italic>Candida</jats:italic> yeast are recognized and taken up by macrophages via phagocytosis. Macrophage surface receptors bind to specific components of the <jats:italic>Candida</jats:italic> cell wall. Following phagocytosis, <jats:italic>Candida</jats:italic> can respond to the host's intracellular environment by switching from a yeast to a hyphal morphology facilitating escape from macrophages and allowing subsequent invasion of host tissues. Various disruptions of <jats:italic>Candida</jats:italic> 's ability to form hyphae have been shown to reduce virulence and fitness in the host. Our previous work concluded that <jats:styled-content style=\"fixed-case\"> <jats:italic>Candida albicans</jats:italic> </jats:styled-content> cells lacking AP‐2 ( <jats:italic>apm4Δ/Δ)</jats:italic> , an endocytic adaptor complex, have increased cell wall chitin and morphologically defective hyphae in vitro. Increased chitin has been correlated with decreased recognition by macrophages, possibly due to masking of cell wall β‐glucan, the target for the Dectin‐1 immune receptor. Here we test the virulence profiles of <jats:italic>apm4Δ/Δ</jats:italic> mutant, demonstrating a surprising increase in macrophage phagocytosis that does not occur due to the elevated exposure of β‐glucan, highlighting the importance of cell wall components beyond chitin and glucan for macrophage engagement and uptake. Furthermore, the <jats:italic>apm4</jats:italic> mutant exhibited parasitism of macrophages, surviving and proliferating within the phagosome, a phenotype that was then replicated with a well‐characterized yeast locked mutant, demonstrating the further complexity of <jats:italic> <jats:styled-content style=\"fixed-case\">C. albicans</jats:styled-content> ' </jats:italic> ability to evade macrophage responses. Finally, the combined phenotype of reduced hyphal formation but continued proliferation resulted in reduced virulence despite an equivalent burden of infection with wild‐type <jats:italic>Candida</jats:italic> infection, as determined using a zebrafish larval model of candidiasis.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"227 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427526","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}