Infection and Immunity最新文献

Cell death pathways in response to Mycobacterium tuberculosis and other mycobacterial infections. 响应结核分枝杆菌和其他分枝杆菌感染的细胞死亡途径。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-09-09 DOI: 10.1128/iai.00401-25

Md Atik Faysal, Mostafa Hanafy, Denise K Zinniel, Fatema Yeasmin Tanni, Ezhumalai Muthukrishnan, Govardhan Rathnaiah, Raul G Barletta

{"title":"Cell death pathways in response to Mycobacterium tuberculosis and other mycobacterial infections.","authors":"Md Atik Faysal, Mostafa Hanafy, Denise K Zinniel, Fatema Yeasmin Tanni, Ezhumalai Muthukrishnan, Govardhan Rathnaiah, Raul G Barletta","doi":"10.1128/iai.00401-25","DOIUrl":"10.1128/iai.00401-25","url":null,"abstract":"Cell death mechanisms play a fundamental role in mycobacterial pathogenesis. We critically reviewed 94 research manuscripts, 44 review articles, and 4 book chapters to analyze important discoveries, background literature, and potential shortcomings in the field. The focus of this review is the pathogen Mycobacterium tuberculosis (Mtb) and other Mtb and Mycobacterium avium complex microorganisms. Virulent strains hijack cell death processes by inhibiting autophagy, apoptosis, and pyroptosis while eliciting necrosis and ferroptosis to multiply intracellularly and spread within and between hosts. In addition, virulent strains may induce apoptosis in epithelial cells or secondary infected macrophages to spread. Autophagy does not control Mtb intracellular replication in vivo but suppresses macrophage and T cell responses in Mtb infections, with a predominant role in preventing neutrophil infiltration. In contrast, attenuated vaccine strains promote apoptosis in macrophages, leading to the activation of innate immunity and, eventually, the acquired immune response. Although Mtb infection activates necroptosis, studies with mutant cell lines have indicated that this process is not essential for cell lysis and that Mtb promotes unprogrammed necrosis. Ferroptosis is discussed in the context of necrotic processes involving lipid peroxidation. Recent research indicated that pyroptosis is more akin to apoptosis as Mtb proteins induce cell membrane repair to prevent inflammasome activation. In the supplementary tables, homologs of mycobacterial cell death pathways and virulence factors were identified using a basic local alignment search tool protein followed by a conserved domain database search to determine the presence of functional domains. Finally, prospects for therapeutic interventions are discussed.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0040125"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of group B Streptococcus infection and vaginal cell inflammatory signaling in vitro by Lactobacillus crispatus-loaded electrospun fibers. 负载马铃薯乳杆菌的静电纺丝纤维对B群链球菌感染和阴道细胞炎症信号的体外调节。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-08-27 DOI: 10.1128/iai.00170-25

Nagwa El-Baz, Anthony Kyser, Mohamed Y Mahmoud, Christopher Z Farrell, Sierra Ginocchio, Hermann B Frieboes, Ryan S Doster

{"title":"Modulation of group B Streptococcus infection and vaginal cell inflammatory signaling in vitro by Lactobacillus crispatus-loaded electrospun fibers.","authors":"Nagwa El-Baz, Anthony Kyser, Mohamed Y Mahmoud, Christopher Z Farrell, Sierra Ginocchio, Hermann B Frieboes, Ryan S Doster","doi":"10.1128/iai.00170-25","DOIUrl":"10.1128/iai.00170-25","url":null,"abstract":"Vaginal colonization by Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a major risk factor for ascending infections, preterm birth, and neonatal sepsis. Current GBS prevention efforts include routine GBS perinatal screening and intrapartum antibiotic prophylaxis, which decrease the rate of early-onset neonatal sepsis, but have drawbacks that include impacting the infant's developing microbiome. Lactobacillus-dominant vaginal microbiomes provide protection against pathogens such as GBS, and using probiotics as an antibiotic-free approach to limit GBS colonization is of increasing interest. In this study, we investigated the ability of Lactobacillus crispatus-loaded electrospun fibers to deliver live L. crispatus cells in an in vitro vaginal epithelial cell model, modulate GBS infection establishment and persistence, and alter vaginal cell inflammatory signaling. Our data demonstrate that electrospun fibers deliver viable L. crispatus to the surface of vaginal epithelial cells and that L. crispatus modulates vaginal cell inflammatory signaling by decreasing inflammatory IL-8 release and increasing anti-inflammatory IL-1RA secretion during established GBS infection. Treatment of pre-established GBS infection with electrospun fibers with or without L. crispatus decreased GBS burden at 24 hours, suggesting L. crispatus-dependent and -independent anti-GBS activity, and L. crispatus elicited an anti-inflammatory response via IL-1RA release. Overall, the data highlight the potential of electrospun fibers as a feasible probiotic delivery platform with antibacterial activity against GBS and which provides commensal lactobacilli capable of modulating host-pathogen interactions and inflammatory signaling of the vaginal epithelium.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0017025"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alterations in nutrient availability in the lungs during Streptococcus pneumoniae-induced pneumonia. 肺炎链球菌引起的肺炎期间肺部营养物质可用性的改变。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 DOI: 10.1128/iai.00380-25

Hansol Im, Vipin Chembilikandy, Adonis D'Mello, Madison Pearson, Hervé Tettelin, Carlos J Orihuela

{"title":"Alterations in nutrient availability in the lungs during Streptococcus pneumoniae-induced pneumonia.","authors":"Hansol Im, Vipin Chembilikandy, Adonis D'Mello, Madison Pearson, Hervé Tettelin, Carlos J Orihuela","doi":"10.1128/iai.00380-25","DOIUrl":"https://doi.org/10.1128/iai.00380-25","url":null,"abstract":"Streptococcus pneumoniae is a leading cause of pneumonia. Importantly, the extent and impact of changes in the infected airway on bacterial nutrient availability and gene expression are not known. Utilizing untargeted UPLC-ESI-MS/MS metabolomics, we comprehensively characterized the metabolic landscape in the airway across early, mid, and severe stages of pneumococcal pneumonia. This revealed that dynamic shifts in metabolites occurred during pneumonia, with an initial influx of metabolites at the early stage, followed by declines as the disease progressed. Specific host metabolic perturbations were indicative of purine dysregulation, cellular stress, and outright tissue injury. Levels of glucose, a known modulator of pneumococcal capsule production, were highest at the early disease stage and then declined as the disease progressed, overlaying general metabolite trends. Concurrent bacterial transcriptome profiling was performed using a NanoString nCounter custom panel of 66 genes selected for their importance to metabolism, virulence, and stress response; 9% of which had disease-stage significant differences in gene expression. This analysis revealed remarkably high expression of spxB, the gene encoding pyruvate oxidase, at the severe stage of pneumonia compared to the mid-stage pneumonia, consistent with a drop in glucose levels and indicative of a shift toward mixed fermentation and the increased production of hydrogen peroxide. Our study improves our understanding of how pneumococcal infection alters the lung environment, driving profound metabolic shifts that, in turn, influence bacterial phenotypes. This detailed understanding of host-pathogen metabolic interactions offers valuable insights into novel therapeutic strategies.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0038025"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic transformation of Gardnerella species and characterization of vaginolysin and sialidase mutants. 加德纳菌种的遗传转化及阴道溶素和唾液酸酶突变体的鉴定。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-08-21 DOI: 10.1128/iai.00299-25

Amy K Klimowicz, Erin M Garcia, Kimberly K Jefferson, Joseph P Dillard

{"title":"Genetic transformation of Gardnerella species and characterization of vaginolysin and sialidase mutants.","authors":"Amy K Klimowicz, Erin M Garcia, Kimberly K Jefferson, Joseph P Dillard","doi":"10.1128/iai.00299-25","DOIUrl":"10.1128/iai.00299-25","url":null,"abstract":"Bacterial vaginosis (BV) is the most prevalent vaginal disorder in women of childbearing age and causes pregnancy complications, including preterm birth, amnionitis, and postpartum endometritis. BV also interferes with sexual health and increases stress. BV is a vaginal dysbiosis that occurs when Lactobacillus species are displaced by facultative and anaerobic bacterial species, including Gardnerella, Prevotella, Fannyhessea, Sneathia, Megasphaera, Mycoplasma, and others. Species of Gardnerella increase just prior to the onset of symptoms and are considered to play major roles in the development and transmission of BV. However, Gardnerella species have remained genetically intractable, limiting investigations of their virulence mechanisms. Here, we describe methods for genetic manipulation of Gardnerella. Through trial and error, we optimized methods for electrotransformation of Gardnerella and created methods for making mutations and complements. We mutated the gene for the toxin vaginolysin (vly) in G. vaginalis and the gene for sialidase nanH3 in G. pickettii. A vly point mutant was tested in human cervix tissue and found to lack lytic activity. The nanH3 mutant lost sialidase and mucus degradation activity. Overall, this genetic toolkit opens a door for molecular characterization of Gardnerella and its mechanisms in BV.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0029925"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The emerging view on the roles of butyrate in Clostridioides difficile pathogenesis. 关于丁酸盐在艰难梭菌发病机制中的作用的新观点。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-09-24 DOI: 10.1128/iai.00047-25

Horia A Dobrila, Andrew J Hryckowian

{"title":"The emerging view on the roles of butyrate in Clostridioides difficile pathogenesis.","authors":"Horia A Dobrila, Andrew J Hryckowian","doi":"10.1128/iai.00047-25","DOIUrl":"10.1128/iai.00047-25","url":null,"abstract":"The Centers for Disease Control and Prevention classifies Clostridioides difficile as an urgent threat to the nation's health, as it causes 450,000 infections, 15,000 deaths, and 1 billion dollars in excess healthcare costs per year in the United States. Current treatments for C. difficile infections (CDIs) are antibiotics and, in recurrent cases, microbiome restoration therapy (MRT). Antibiotics contribute to antibiotic resistance and recurrent CDIs. Although MRTs (e.g., defined consortia of microbes or fecal transplant) are increasingly accessible, the long-term sustainability and accessibility of these treatments remain to be determined. These limitations highlight the need for more precise strategies for coping with CDI. Because a disrupted (dysbiotic) gut microbiome is the primary risk factor for CDI, a better understanding of the interactions between C. difficile, the microbiome, and the host will aid the development of such treatments. Butyrate is a prominent microbiome-host co-metabolite that is influenced by host dietary fiber intake and differentiates healthy from dysbiotic gut ecosystems. Emerging evidence supports that butyrate is a key determinant of C. difficile fitness and pathogenesis. Here, we review the current literature and gaps in knowledge about how butyrate-rich gut environments exclude C. difficile, and how butyrate impacts C. difficile growth, metabolism, toxin production/release, and sporulation. We further discuss the implications of continued study of butyrate's impacts on CDI, including the eventual development of new strategies to mitigate CDI in at-risk human populations.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0004725"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The host calcium system contributes to intracellular Rickettsia pathogenesis. 宿主钙系统参与细胞内立克次体发病。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-08-21 DOI: 10.1128/iai.00363-25

Jinyi C Zhu, Jack H Cook, Mustapha Dahmani, Sean P Riley

{"title":"The host calcium system contributes to intracellular Rickettsia pathogenesis.","authors":"Jinyi C Zhu, Jack H Cook, Mustapha Dahmani, Sean P Riley","doi":"10.1128/iai.00363-25","DOIUrl":"10.1128/iai.00363-25","url":null,"abstract":"Bacteria in the genus Rickettsia are obligate intracellular parasites of the eukaryotic cytoplasm. Pathogenic Rickettsia species are exquisitely evolved to only proliferate within eukaryotic host cells, particularly within endothelial cells of the mammalian vasculature. Through evolution in this very specific niche, Rickettsia have developed an inextricable dependence on multiple host functions. This absolute dependence on host cell biology offers a potential strategy for antibacterial development called host-targeted therapeutics. A previous screen of compounds that specifically target mammalian cell biology indicated that host-targeted calcium channel blockers (CCBs) inhibit Rickettsia conorii proliferation within human cells. CCBs are routinely prescribed to human patients as antihypertensives or antianginals that function by disrupting the calcium ion equilibrium in vesicula/cardiac smooth muscle cells. To further investigate the potential anti-Rickettsia activities of CCBs, we sought to define the interaction between pathogenic Rickettsia and the host Ca2+ system. Achieved data demonstrate that CCBs inhibit Rickettsia proliferation within endothelial cells, and that physical disruption of the host Ca2+ ion gradient also disrupts Rickettsia growth. Additional analyses reveal that Rickettsia infection leads to a rapid and persistent disruption of the host Ca2+ equilibrium. By querying Rickettsia pathogenesis, we demonstrate that some CCBs marginally disrupt rickettsial adherence to the host cell or induce apoptosis. However, all tested CCBs universally and significantly disrupt the ability of Rickettsia to polymerize actin. Together, these data demonstrate that CCBs possess anti-Rickettsia properties that function by disrupting rickettsial actin polymerization, and these results highlight the complex interdependence of Rickettsia and host cell biology.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0036325"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acquired tick resistance in Peromyscus leucopus alters Ixodes scapularis infection. 获得性蜱抗药性改变肩胛骨硬蜱感染。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-09-03 DOI: 10.1128/iai.00246-25

Elis A Fisk, Cassie J Leonard, Kristin L Rosche, Elisabeth Ramirez-Zepp, Jeffrey R Abbott, Jeb P Owen, Dana K Shaw

{"title":"Acquired tick resistance in Peromyscus leucopus alters Ixodes scapularis infection.","authors":"Elis A Fisk, Cassie J Leonard, Kristin L Rosche, Elisabeth Ramirez-Zepp, Jeffrey R Abbott, Jeb P Owen, Dana K Shaw","doi":"10.1128/iai.00246-25","DOIUrl":"10.1128/iai.00246-25","url":null,"abstract":"Ticks are obligate hematophagous parasites and pathogen vectors responsible for morbidity and mortality worldwide. Ixodes scapularis is a vector for at least seven pathogens relevant to human and animal health, including the Lyme disease microbe, Borrelia burgdorferi, and the causative agent of anaplasmosis, Anaplasma phagocytophilum. Tick-host interactions affect the maintenance of tick-borne pathogens in a population. Here, we report that repeated I. scapularis larval infestations on the wild host species Peromyscus leucopus lead to immune-mediated rejection of the tick, a phenomenon termed acquired tick resistance (ATR). On previously infested mice, we observed that larval feeding success was reduced by over 50%, and fed larvae had decreased blood meal weights compared to larvae fed on naïve hosts. Over sequential infestations, mice exhibited increasingly severe inflammation at tick bite sites characterized by an influx of basophils, eosinophils, neutrophils, and T lymphocytes. Larvae fed on sensitized mice ingested higher quantities of host leukocytes when compared to ticks fed on naïve hosts, which rarely ingested nucleated cells. When challenged with B. burgdorferi or A. phagocytophilum, larvae fed on sensitized mice ingested more bacteria. Altogether, we demonstrate that reservoir host species develop ATR against larval I. scapularis, which reduces tick feeding success and affects pathogen ingestion by larvae. These results indicate that ATR could impact Ixodes population dynamics, prevalence of infected ticks, and pathogen circulation in the wild.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0024625"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Host-directed therapeutic targets in macrophages and their ligands against mycobacteria tuberculosis. 巨噬细胞及其配体抗结核分枝杆菌的宿主靶向治疗靶点。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-08-25 DOI: 10.1128/iai.00063-25

Jin Li, Yanmei Wang, Lei He, Luchuan Yang, Tao Tao, Lang Bai, Youfu Luo

{"title":"Host-directed therapeutic targets in macrophages and their ligands against mycobacteria tuberculosis.","authors":"Jin Li, Yanmei Wang, Lei He, Luchuan Yang, Tao Tao, Lang Bai, Youfu Luo","doi":"10.1128/iai.00063-25","DOIUrl":"10.1128/iai.00063-25","url":null,"abstract":"Although current combination regimens of antibiotics have significantly improved tuberculosis (TB) cure rates, substantial challenges persist in the global effort to end TB. These include poor patient compliance, the emergence of drug-resistant strains due to prolonged treatments, and the persistence of latent TB infections. Host-directed therapies (HDTs) have emerged as a promising complementary strategy, leveraging the modulation of host immune responses to combat Mycobacterium tuberculosis (Mtb). Unlike conventional antibiotics, HDTs can enhance therapeutic outcomes by boosting host defense mechanisms, reducing treatment duration and dosage, and minimizing the risk of resistance development. Notably, several HDTs have shown significant efficacy against multidrug-resistant (MDR) Mtb strains, while also mitigating excessive inflammation and lowering relapse rates-achievements that remain elusive with antibiotic regimens alone. This review provides a comprehensive overview of recent advancements in HDTs, focusing on druggable targets and the mechanisms by which these therapies restore or enhance immune functions disrupted by Mtb. By integrating insights into macrophage polarization, metabolic modulation, autophagy promotion, and cell death regulation, HDTs offer innovative and multifaceted approaches to TB treatment. Furthermore, the potential for HDTs to synergize with existing antibiotics underscores their relevance in overcoming current therapeutic limitations. This synthesis aims to inspire further research and development, with the ultimate goal of advancing HDTs as a transformative solution for TB management.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0006325"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Complete deletion of the Chlamydia muridarum putative cytotoxin locus reveals contributions during invasion in tissue culture and oviduct pathology during murine genital tract infection. muridarum衣原体假定的细胞毒素位点的完全缺失揭示了在组织培养和小鼠生殖道感染期间的输卵管病理侵袭过程中的贡献。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-09-22 DOI: 10.1128/iai.00419-25

Lucie H Berclaz, Gracie Eicher, Grace Wieselquist, Akosua Frimpong, Aria Mallare, Rebeccah S Lijek, Kenneth A Fields

{"title":"Complete deletion of the Chlamydia muridarum putative cytotoxin locus reveals contributions during invasion in tissue culture and oviduct pathology during murine genital tract infection.","authors":"Lucie H Berclaz, Gracie Eicher, Grace Wieselquist, Akosua Frimpong, Aria Mallare, Rebeccah S Lijek, Kenneth A Fields","doi":"10.1128/iai.00419-25","DOIUrl":"10.1128/iai.00419-25","url":null,"abstract":"Chlamydiaceae is a family of obligate intracellular bacteria that infect a wide range of human and animal hosts. Chlamydia muridarum is a murine-specific species that has been leveraged as an efficacious model of disease mediated by human-specific Chlamydia trachomatis. Genes within the plasticity zone, a region of the chromosome with increased genetic variation across species and serovars, are speculated to contribute to species-specific pathogenesis. C. muridarum expresses three homologous proteins (TC0437-0439) that show similarity to large clostridial cytotoxins. The putative chlamydial cytotoxins have been proposed to mediate immediate toxicity in highly infected epithelial cells by interfering with actin polymerization. We utilized FRAEM mutagenesis to delete all three putative cytotoxins (tc0437-0439). The null strain retained immediate cytotoxicity but exhibited decreased invasion efficiency in tissue culture. During murine infections of the female genital tract, the absence of the putative cytotoxins caused decreased oviduct pathology and did not impact bacterial burden in the upper genital tract. These results indicate that the putative cytotoxins contribute to infection at the cellular level and in the female genital tract of mice.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0041925"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elevated glucose increases Staphylococcus aureus antibiotic resistance in a cystic fibrosis airway epithelial cell infection model. 在囊性纤维化气道上皮细胞感染模型中，葡萄糖升高会增加金黄色葡萄球菌的抗生素耐药性。

IF 2.8 3区医学

Infection and Immunity Pub Date : 2025-10-14 Epub Date: 2025-09-22 DOI: 10.1128/iai.00178-25

Emily M Hughes, Meghan J Hirsch, Joshua T Huffines, Stefanie Krick, Megan R Kiedrowski

{"title":"Elevated glucose increases Staphylococcus aureus antibiotic resistance in a cystic fibrosis airway epithelial cell infection model.","authors":"Emily M Hughes, Meghan J Hirsch, Joshua T Huffines, Stefanie Krick, Megan R Kiedrowski","doi":"10.1128/iai.00178-25","DOIUrl":"10.1128/iai.00178-25","url":null,"abstract":"In a healthy lung, the airway epithelium regulates glucose transport to maintain low glucose concentrations in the airway surface liquid (ASL). However, hyperglycemia and chronic lung diseases, such as cystic fibrosis (CF), can result in increased glucose in bronchial aspirates. People with CF are also at increased risk of lung infections caused by bacterial pathogens, including methicillin-resistant Staphylococcus aureus. Yet, it is not known how increased airway glucose availability affects bacteria in chronic CF lung infections or impacts treatment outcomes. To model the CF airways, we cultured immortalized CF (CFBE41o-) and non-CF (16HBE) human bronchial epithelial cells at the air-liquid interface (ALI). Glucose concentrations in the basolateral media were maintained at 5.5 or 12.5 mM to mimic a normal and hyperglycemic milieu, respectively. We found that glucose concentrations in the ASL of ALI cultures maintained in normal or high glucose mimicked levels measured in breath condensate assays from people with CF and hyperglycemia. Additionally, we found hyperglycemia increased S. aureus aggregation and antibiotic resistance during infection of cells maintained in high glucose compared to normal glucose conditions. Heightened antibiotic resistance was not observed during in vitro growth with elevated glucose. Limiting glucose with 2-deoxyglucose both decreased aggregation and reduced antibiotic resistance back to levels comparable to non-hyperglycemic conditions. These data indicate that hyperglycemia alters S. aureus growth during infection and may reduce efficacy of antibiotic treatment. Glucose restriction is a potential option that could be explored to limit bacterial growth and improve treatment outcomes in chronic airway infections.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0017825"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0