Infection and Immunity最新文献

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Guanylate-binding protein 5: a promising biomarker and therapeutic target. 鸟苷酸结合蛋白5:一个有前景的生物标志物和治疗靶点。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-11 DOI: 10.1128/iai.00026-25
Jianliang Lu, Wei Wang
{"title":"Guanylate-binding protein 5: a promising biomarker and therapeutic target.","authors":"Jianliang Lu, Wei Wang","doi":"10.1128/iai.00026-25","DOIUrl":"10.1128/iai.00026-25","url":null,"abstract":"<p><p>The guanylate-binding protein (GBP) family, a group of interferon-induced GTPases, is pivotal in pathogen defense, inflammation regulation, and tumor immunity. Among them, GBP5 has emerged as a key player due to its distinctive roles in various diseases. However, existing studies reveal significant gaps, particularly regarding its expression, regulatory mechanisms, and functional dynamics across diverse diseases and patient populations, limiting its reliability as a biomarker or therapeutic target. This review provides a comprehensive synthesis of GBP5 functions across infectious diseases, cancer, immune disorders, and inflammation, with dedicated analysis of its context-dependent functional variability in distinct immune landscapes, genetic backgrounds, and disease progression stages. This systematic evaluation provides a critical foundation for future research, highlighting GBP5's promise as both a biomarker and therapeutic target in precision medicine.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0002625"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tick-borne coinfections modulate CD8+ T cell response and progressive leishmaniosis. 蜱传共感染调节CD8+ T细胞反应和进行性利什曼病。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-07-31 DOI: 10.1128/iai.00182-25
Breanna M Scorza, Danielle Pessôa-Pereira, Felix Pabon-Rodriguez, Erin A Beasley, Kurayi Mahachi, Arin D Cox, Eric Kontowicz, Tyler Baccam, Geneva Wilson, Max C Waugh, Shelbe Vollmer, Angela Toepp, Kavya Raju, Ogechukwu C Chigbo, Jonah Elliff, Greta Becker, Karen I Cyndari, Serena Tang, Grant Brown, Christine A Petersen
{"title":"Tick-borne coinfections modulate CD8<sup>+</sup> T cell response and progressive leishmaniosis.","authors":"Breanna M Scorza, Danielle Pessôa-Pereira, Felix Pabon-Rodriguez, Erin A Beasley, Kurayi Mahachi, Arin D Cox, Eric Kontowicz, Tyler Baccam, Geneva Wilson, Max C Waugh, Shelbe Vollmer, Angela Toepp, Kavya Raju, Ogechukwu C Chigbo, Jonah Elliff, Greta Becker, Karen I Cyndari, Serena Tang, Grant Brown, Christine A Petersen","doi":"10.1128/iai.00182-25","DOIUrl":"10.1128/iai.00182-25","url":null,"abstract":"<p><p><i>Leishmania infantum</i> causes human visceral leishmaniasis and leishmaniosis (CanL) in reservoir host, dogs. As infection progresses to disease in both humans and dogs, there is a shift from controlling type 1 immunity to a regulatory, exhausted T cell phenotype. In endemic areas, the association between tick-borne coinfections (TBCs) and <i>Leishmania</i> diagnosis and/or clinical severity has been demonstrated. To identify immune factors correlating with disease progression, we prospectively evaluated a cohort of <i>L. infantum</i>-infected dogs from 2019 to 2022. The cohort was TBC-negative with asymptomatic leishmaniosis at the time of enrollment. We measured TBC serology, anti-<i>Leishmania</i> antigen T cell immunity, CanL serological response, parasitemia, and disease severity to probe how nascent TBC perturbs the immune state. At the conclusion, TBC+ dogs with CanL experienced greater increases in anti-<i>Leishmania</i> antibody reactivity and parasite burden compared to dogs that did not have incident TBC during the study. TBC+ dogs were twice as likely to experience moderate (LeishVet stage 2) or severe/terminal disease (LeishVet stage 3/4). Prolonged exposure to TBC was associated with a shift in <i>Leishmania</i> antigen-induced interferon gamma (IFN-γ)/interleukin-10 (IL-10) and enhanced CD8 T cell proliferation. Frequency of proliferating CD8 T cells significantly correlated with parasitemia and antibody reactivity. TBC exacerbated parasite burden and immune exhaustion. These findings highlight the need for combined vector control efforts as prevention programs for dogs in <i>Leishmania</i> endemic areas to reduce transmission to humans. Public health education efforts should aim to increase awareness of the connection between TBC and leishmaniosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0018225"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Loss of pulmonary tissue protection and neutrophil microbicidal defects promote severe Aspergillus fumigatus infection during influenza A virus infection. 在甲型流感病毒感染期间,肺组织保护功能的丧失和中性粒细胞杀微生物缺陷促进了严重的烟曲霉感染。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-11 DOI: 10.1128/iai.00234-25
Zhihan Wang, Taylor Schmit, Kai Guo, Jitendra Kumar Tripathi, Zahrasadat Navaeiseddighi, Antariksh Tyagi, Ramkumar Mathur, Junguk Hur, Donald Jurivich, Nadeem Khan
{"title":"Loss of pulmonary tissue protection and neutrophil microbicidal defects promote severe <i>Aspergillus fumigatus</i> infection during influenza A virus infection.","authors":"Zhihan Wang, Taylor Schmit, Kai Guo, Jitendra Kumar Tripathi, Zahrasadat Navaeiseddighi, Antariksh Tyagi, Ramkumar Mathur, Junguk Hur, Donald Jurivich, Nadeem Khan","doi":"10.1128/iai.00234-25","DOIUrl":"10.1128/iai.00234-25","url":null,"abstract":"<p><p>Invasive pulmonary aspergillosis (IPA) is a severe fungal disease caused by <i>Aspergillus fumigatus</i> (<i>Af</i>) that may spread hematogenously to extrapulmonary organs. IPA is typically associated with a broad spectrum of immunocompromised conditions and constitutes a high mortality rate. While the association of influenza as a risk for secondary bacterial infections is well appreciated, emerging evidence indicates that influenza-hospitalized patients demonstrate increased susceptibility to severe aspergillosis infection. In this study, we developed a murine Influenza A Virus (IAV)-<i>Af</i> co-infection model and investigated the role of IAV host response in promoting invasive <i>Af</i> infection. Our data show that IAV temporarily suppresses neutrophil recruitment in the early phase of <i>Af</i> co-infection (24 hours), followed by a subsequent increase in neutrophil levels (48 hours). RNA sequencing analysis of neutrophils from IAV-<i>Af</i> co-infected lungs (48 hours) reveals enrichment of pathways regulating inflammatory responses and phagocytosis. Despite higher inflammatory response and phagocytosis, the host response from IAV-<i>Af</i> co-infected lungs had suppressive effects on neutrophil conidial killing, correlating with lung fungal load and invasion. However, the increased fungal invasion observed at 24 hours post co-infection, despite similar fungal loads in both groups (<i>Af</i> vs. IAV-<i>Af</i>), suggests that IAV-induced pathologic lung inflammation and vascular damage likely promote <i>Af</i> invasiveness during the initial phase of co-infection, and subsequently, the defects in neutrophil fungicidal response and exacerbated lung damage lead to sustained and fatal IPA pathogenesis in the later phase of co-infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0023425"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR-based genetic tools for the study of host-microbe interactions. 基于crispr的宿主-微生物相互作用研究的遗传工具。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-04 DOI: 10.1128/iai.00510-24
Martin Echavarria Galindo, Yong Lai
{"title":"CRISPR-based genetic tools for the study of host-microbe interactions.","authors":"Martin Echavarria Galindo, Yong Lai","doi":"10.1128/iai.00510-24","DOIUrl":"10.1128/iai.00510-24","url":null,"abstract":"<p><p>CRISPR-based genetic tools have revolutionized our ability to interrogate and manipulate genes. These tools can be applied to both host and microbial cells, and their use can enhance our understanding of the dynamic nature of host-microbe interactions by uncovering their genetic underpinnings. As reviewed here, CRISPR-based tools are being used to explore the microbiome in an efficient, accurate, and high-throughput manner. By employing CRISPR screens, targeted genome editing, and recording systems to the study of host cells and microorganisms, we can gain critical insights into host defense mechanisms, potential vulnerabilities, and microbial pathogenesis, as well as essential or condition-specific genes involved in host-microbe interactions. Additionally, CRISPR-based genetic tools are being used in animal models to study host-microbe interactions <i>in vivo</i>. Recent advancements in CRISPR-derived technology can be combined with emerging techniques, such as single-cell RNA sequencing, to examine the complex interactions between hosts and microbes, shedding light on the role of the microbiome in health and disease. This review aims to provide a comprehensive overview of how these cutting-edge genetic tools are being used to investigate host-microbial systems, as well as their current limitations. Current research is likely to yield even more advanced genetic toolkits than those presently available, and these can serve researchers in identifying and exploring new therapeutic targets for diseases related to host-microbe interactions.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0051024"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the vaginal ecosystem: insights into host-microbe interactions and microbial community dynamics. 探索阴道生态系统:对宿主-微生物相互作用和微生物群落动态的见解。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-11 DOI: 10.1128/iai.00499-24
Emily F Landolt, Jéssica da Conceição Mendonça, Abbey E Behler, Stephen W Lumsdaine, Tamanna Jafar, Lindsey R Burcham
{"title":"Exploring the vaginal ecosystem: insights into host-microbe interactions and microbial community dynamics.","authors":"Emily F Landolt, Jéssica da Conceição Mendonça, Abbey E Behler, Stephen W Lumsdaine, Tamanna Jafar, Lindsey R Burcham","doi":"10.1128/iai.00499-24","DOIUrl":"10.1128/iai.00499-24","url":null,"abstract":"<p><p>The vaginal tract is a complex environment that changes throughout various life stages. Recent advances have improved our understanding of the vaginal microbiota and the influence of host factors on microbial colonization. The vaginal niche is characterized by unique qualities such as high abundances of glycogen and mucin, low pH, active cellular immunity, and fluctuations in hormone signaling that support a complex microbiota. While traditionally thought to be dominated by <i>Lactobacillus</i> species, emerging research highlights a more diverse microbiota, including both commensal and potentially pathogenic microbes. Given the interconnectedness of the microbial and host factors in this environment, minor shifts can lead to significant downstream effects on health. This review takes an ecosystems approach to explore the multifaceted relationship between the vaginal mucosa, the microbiota, and influences of environmental factors on shaping the two. We discuss the contribution of hormone signaling in shaping microbial communities, concepts of vaginal community stability and dysbiosis, and the emerging understanding of microbial metabolism and cross-feeding dynamics within the vaginal tract. Additionally, we will examine the interactions between microbes and immune cells in the vaginal mucosa, including mechanisms by which the immune system modulates the local environment. By considering the feedback loops between the host and the resident microbiota, we propose key knowledge gaps and suggest interdisciplinary avenues for future research aimed at improving our understanding of vaginal health and disease. Understanding these complex interactions is important for advancing vaginal healthcare across all individuals.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0049924"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Candida albicans gastrointestinal colonization resistance: a host-microbiome balancing act. 白色念珠菌胃肠道定植抵抗:宿主-微生物平衡行为。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-11 DOI: 10.1128/iai.00610-24
Derek J Bays, Hannah P Savage
{"title":"<i>Candida albicans</i> gastrointestinal colonization resistance: a host-microbiome balancing act.","authors":"Derek J Bays, Hannah P Savage","doi":"10.1128/iai.00610-24","DOIUrl":"10.1128/iai.00610-24","url":null,"abstract":"<p><p>While <i>Candida albicans</i> is a common, commensal yeast colonizing 50%-60% of humans, it has the potential to expand in the gastrointestinal tract and enter the blood stream resulting in invasive candidiasis. Invasive candidiasis carries a mortality approaching 50%, especially in the most vulnerable, immunocompromised population. Antibacterial use causes an increase in <i>C. albicans</i> gastrointestinal colonization, indicating that the colonic microbiota plays a major role in preventing an uncontrolled expansion, a phenomenon known as colonization resistance. Antibacterials, medications, diet, and co-morbid conditions can all alter the microbiome, creating an altered environment known as dysbiosis. Our understanding of the microbiome continues to advance, and there is increasing evidence that the interactions that the microbiome has on the host are vital in maintaining colonization resistance to pathogens including <i>C. albicans</i>. This review will focus on colonization resistance to <i>C. albicans</i> within the gastrointestinal tract. The scope includes the benefits and consequences of <i>C. albicans</i> colonization, interkingdom interactions of the microbiome on <i>C. albicans</i>, microbiome-host interactions and how these modulate <i>C. albicans</i> colonization, and the impact of medications and diet on colonization resistance.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0061024"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Infections as ecosystems: community metabolic interactions in microbial pathogenesis. 作为生态系统的感染:微生物发病机制中的群落代谢相互作用。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-04 DOI: 10.1128/iai.00530-24
Aanuoluwa E Adekoya, Shannon R West, Sydney K Arriaga, Carolyn B Ibberson
{"title":"Infections as ecosystems: community metabolic interactions in microbial pathogenesis.","authors":"Aanuoluwa E Adekoya, Shannon R West, Sydney K Arriaga, Carolyn B Ibberson","doi":"10.1128/iai.00530-24","DOIUrl":"10.1128/iai.00530-24","url":null,"abstract":"<p><p>Microbes rarely exist alone; instead, they live in dynamic multi-species communities with a range of metabolic capacities. To establish within a polymicrobial community, an organism must compete with the other members of the community for space and nutrients. In addition, microbes form complex metabolic interdependencies in polymicrobial environments, and these nutrient exchanges are central to overall community function. Interactions between microbial community members dictate key processes, including nutrient cycling, tolerance to disturbances, and disease progression, and these interactions are known to depend on the environment in which they are measured. Therefore, understanding these ecological interactions is fundamental to our understanding of community composition, function, and impacts on disease. In this mini-review, we will describe the mechanisms microbes use to exchange nutrients in host-associated environments, with a focus on the oral and respiratory tracts. We will particularly emphasize the environmental factors that influence community composition and how interactions between organisms, ranging from cooperation to competition, impact nutrient bioavailability and overall community function during infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0053024"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural and functional characterization of IdeC, a novel IgG-specific protease of Streptococcus canis. 犬链球菌新型igg特异性蛋白酶IdeC的结构和功能表征
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-07-31 DOI: 10.1128/iai.00248-25
Saoirse Walsh, Antje-Maria Lapschies, Vega Miguel-Ruano, María T Batuecas, Iván Acebrón-Ávalos, Thomas P Kohler, Sven Hammerschmidt, Inga Eichhorn, Juan A Hermoso, Marcus Fulde
{"title":"Structural and functional characterization of IdeC, a novel IgG-specific protease of <i>Streptococcus canis</i>.","authors":"Saoirse Walsh, Antje-Maria Lapschies, Vega Miguel-Ruano, María T Batuecas, Iván Acebrón-Ávalos, Thomas P Kohler, Sven Hammerschmidt, Inga Eichhorn, Juan A Hermoso, Marcus Fulde","doi":"10.1128/iai.00248-25","DOIUrl":"10.1128/iai.00248-25","url":null,"abstract":"<p><p><i>Streptococcus canis</i> is an important opportunistic pathogen of cats, dogs, and cows, which can cause a range of infections, ranging from skin and soft tissue infections to septicemia and endocarditis. As a zoonotic agent, <i>S. canis</i> has also recently been implicated in serious human infections, following trauma or immunosuppression. In this work, we describe a novel protease of <i>S. canis</i>, termed IdeC (<u>I</u>mmunoglobulin G <u>d</u>egrading <u>e</u>nzyme of <i>S. <u>c</u>anis</i>), which may be involved in bacterial immune evasion. The cleaving ability of IdeC against IgG from various species was assessed; this revealed that IdeC successfully cleaved canine, feline, and human IgG. We also confirmed that IdeC is a cysteine protease, similar to IdeS of <i>Streptococcus pyogenes</i>. Investigation of the cleavage site in IgG sequences showed that it is highly conserved across IgGs from all species tested. From this analysis, it was determined that IdeC cleavage occurs between the CH2 and hinge regions of IgG. Interestingly, feline IgG was consistently cleaved with the highest efficiency, with human and canine IgG displaying less efficient cleavage. High-resolution crystal structures of two IdeC constructs provided insights into the catalytic machinery and substrate recognition. Modeling of the full-length IdeC:IgG complexes for human, canine, and feline cases explains the mechanism of action of the protease and reveals the molecular basis for the observed cleavage preference for feline IgG. Understanding and managing <i>S. canis</i> as a pathogen is important in both veterinary and human medicine, as this bacterium underscores the need for awareness of zoonotic transmission.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0024825"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Yersinia pestis BipA is a novel regulator of pesticin and a type 6 secretion system. 鼠疫耶尔森菌BipA是一种新型的农药调节剂和6型分泌系统。
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-11 DOI: 10.1128/iai.00191-25
Madeleine G Scott, Wanfeng Guo, Jon S Blevins, Kenneth T Appell, Roger D Pechous
{"title":"<i>Yersinia pestis</i> BipA is a novel regulator of pesticin and a type 6 secretion system.","authors":"Madeleine G Scott, Wanfeng Guo, Jon S Blevins, Kenneth T Appell, Roger D Pechous","doi":"10.1128/iai.00191-25","DOIUrl":"10.1128/iai.00191-25","url":null,"abstract":"<p><p><i>Yersinia pestis</i> is a gram-negative bacterium and the causative agent of bubonic, septicemic, and pneumonic plague. <i>Y. pestis</i> is most commonly transmitted to humans by infected fleas that deposit the bacteria into the dermis at the bite site, leading to bubonic plague. The bacteria ultimately access the bloodstream, and after deposition in the lung, can be transmitted person-to-person through infectious respiratory droplets, resulting in primary pneumonic plague, a highly lethal and rapidly progressing pneumonia. Pathogenesis is mediated by a suite of chromosomally encoded and plasmid-borne virulence factors, and infection is maintained by temperature-dependent coordinated modifications in gene expression that facilitate bacterial survival in both the flea and mammalian hosts. BipA (BPI-inducible protein A) is a highly conserved translational GTPase that is a <i>Y. pestis</i> virulence factor. BipA modulates protein expression under stress conditions, and its deletion renders <i>Y. pestis</i> more sensitive to killing by neutrophils and attenuates bacterial growth in a murine infection model of pneumonic plague. In the work described here, we show that BipA also regulates specific <i>Y. pestis</i> proteins at flea/environmental temperatures. We show that BipA is responsible for the induction of a recently described type 6 secretion system (T6SS), as well as the transcriptional regulator RovC. We also show that BipA regulates the production of the known <i>Y. pestis</i> bacteriocin pesticin, and that bacteria lacking BipA have a defect in competition not solely attributable to the T6SS or pesticin. Our results show that in addition to its role in the mammalian host, regulation of specific proteins by BipA also likely contributes to bacterial survival during the flea/environmental phase, where <i>Y. pestis</i> must compete with other species of bacteria within a particular niche.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0019125"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Breaking down barriers: is intestinal mucus degradation by Akkermansia muciniphila beneficial or harmful? 打破屏障:嗜粘阿克曼氏菌降解肠道粘液是有益还是有害?
IF 2.8 3区 医学
Infection and Immunity Pub Date : 2025-09-09 Epub Date: 2025-08-11 DOI: 10.1128/iai.00503-24
Anna M Tingler, Melinda A Engevik
{"title":"Breaking down barriers: is intestinal mucus degradation by <i>Akkermansia muciniphila</i> beneficial or harmful?","authors":"Anna M Tingler, Melinda A Engevik","doi":"10.1128/iai.00503-24","DOIUrl":"10.1128/iai.00503-24","url":null,"abstract":"<p><p><i>Akkermansia muciniphila</i> is a specialized mucin-degrading bacterium that plays a pivotal role in gut health and disease. This review examines the dualistic nature of <i>A. muciniphila</i> mucin degradation, exploring its potential benefits and risks. As a mucin specialist, <i>A. muciniphila</i> uses glycosyl hydrolases and mucinases to degrade mucins, producing metabolites like short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), succinate, and other compounds. These metabolites benefit host health and cross-feed other commensal microbes, such as butyrate producers. <i>A. muciniphila</i> levels are inversely correlated with several disease states, such as obesity, diabetes, and inflammatory states, and administration of <i>A. muciniphila</i> has been found by several groups to restore and maintain gut homeostasis. However, under certain conditions, such as low dietary fiber or conditions with an altered gut microbiota, excessive mucin degradation by <i>A. muciniphila</i> can compromise the mucus barrier, increasing susceptibility to inflammation, infection, and pathogenic overgrowth. Elevated <i>A. muciniphila</i> levels have been associated with various diseases and medications, including graft versus host disease (GVHD) and irradiation, and shown to exacerbate infections by enteric pathogens. The context-dependent effects of <i>A. muciniphila</i> and mucin degradation underscore the need for a nuanced understanding of its interactions with the host and microbial community. This review aims to provide a balanced perspective on the implications of gut microbial mucus degradation, highlighting that it can be good, and it can be bad depending on the context.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0050324"},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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