Infection and Immunity最新文献_第2页

HDAC6 inhibition reduces Pseudomonas aeruginosa adherence and internalization in cystic fibrosis epithelial cells via microtubule stabilization. 抑制HDAC6通过微管稳定减少囊性纤维化上皮细胞中的铜绿假单胞菌粘附和内化。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-12 DOI: 10.1128/iai.00225-25

Kathleen L Boyne, Conor Broeking, Mark Blackstone, Sruthi Singaraju, Thomas J Kelley, Deborah A Corey, Patrick C Seed

{"title":"HDAC6 inhibition reduces Pseudomonas aeruginosa adherence and internalization in cystic fibrosis epithelial cells via microtubule stabilization.","authors":"Kathleen L Boyne, Conor Broeking, Mark Blackstone, Sruthi Singaraju, Thomas J Kelley, Deborah A Corey, Patrick C Seed","doi":"10.1128/iai.00225-25","DOIUrl":"https://doi.org/10.1128/iai.00225-25","url":null,"abstract":"Pseudomonas aeruginosa is a common opportunistic pathogen that causes chronic lung infections in individuals with cystic fibrosis. Despite advances in therapies that restore cystic fibrosis transmembrane conductance regulator function, persistent colonization of the airway remains a major clinical challenge. Reduced clearance of P. aeruginosa from the cystic fibrosis airway has been associated with the increased activity of histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase that decreases microtubule acetylation and stability. In this study, we investigated the role of HDAC6 in modulating interactions between P. aeruginosa and cystic fibrosis airway epithelial cells. Pharmacologic inhibition of HDAC6 significantly reduced bacterial adherence in both mouse and human cystic fibrosis epithelial cells. Genetic deletion of HDAC6 produced similar effects, while knockout of a microtubule-stabilizing protein increased bacterial adherence, mimicking the cystic fibrosis phenotype. HDAC6 inhibition also reduced bacterial internalization, although to a lesser extent compared to adherence. These results suggest that microtubule destabilization contributes to the enhanced colonization of cystic fibrosis airways by P. aeruginosa. Targeting host microtubule regulatory pathways, particularly by inhibiting HDAC6, may represent a promising host-directed strategy to limit early bacterial attachment and reduce the risk of chronic infection in cystic fibrosis.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0022525"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712248","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

ABPs: diffusible antibacterial toxins secreted by and active against diverse gram-positive bacteria. ABPs：由多种革兰氏阳性细菌分泌的扩散性抗菌毒素。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-22 DOI: 10.1128/iai.00297-26

Jake Colautti, Daniel Mwangi, Joshua J Woodward, John C Whitney

{"title":"ABPs: diffusible antibacterial toxins secreted by and active against diverse gram-positive bacteria.","authors":"Jake Colautti, Daniel Mwangi, Joshua J Woodward, John C Whitney","doi":"10.1128/iai.00297-26","DOIUrl":"10.1128/iai.00297-26","url":null,"abstract":"Competition between organisms is a ubiquitous feature of life on Earth and a major driver of evolutionary innovation. As Earth's most diverse and abundant organisms, bacteria employ numerous strategies to inhibit the growth of competitors, ranging from the production of diffusible antibiotic metabolites to the secretion of sophisticated protein toxins. Although secreted antibacterial protein toxins have been extensively studied in gram-negative bacteria, analogous systems employed by gram-positive organisms remain comparatively poorly understood. Recent work has shed light on a widespread family of secreted protein toxins associated with co-secreted serine proteases that likely mediate interbacterial competition among gram-positive species. These systems, termed antibacterial protein (ABP) systems, consist of a secreted polymorphic toxin (AbpT), a co-secreted serine protease (AbpP), and a cytoplasmic immunity protein (AbpI). Following proteolytic processing, ABP toxins inhibit the growth of a remarkably diverse range of gram-positive bacteria spanning the phyla Bacillota and Actinomycetota. Existing evidence suggests that these proteins combine the properties of cationic antimicrobial peptides with those of classical polymorphic antibacterial toxins, potentially enabling toxin delivery into distantly related bacteria. In this review, we summarize the current understanding of the organization, mechanisms, and ecology of ABP systems; discuss major outstanding questions regarding toxin import and native biological function; and highlight opportunities for future mechanistic and biotechnological investigation in this emerging field.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0029726"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548791","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

The role of probiotics in restoring and maintaining vaginal microbiome health: a review. 益生菌在恢复和维持阴道微生物群健康中的作用综述。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-06-26 DOI: 10.1128/iai.00011-26

Binaya Krushna Sahu, Sujogya Kumar Panda, Utkalika Mallick, Smita Hasini Panda, Mahesh Chandra Sahu

{"title":"The role of probiotics in restoring and maintaining vaginal microbiome health: a review.","authors":"Binaya Krushna Sahu, Sujogya Kumar Panda, Utkalika Mallick, Smita Hasini Panda, Mahesh Chandra Sahu","doi":"10.1128/iai.00011-26","DOIUrl":"10.1128/iai.00011-26","url":null,"abstract":"The vaginal microbiome is an important aspect of female reproductive health. The dominant microbial species of this ecosystem, Lactobacillus, offers protection from vaginal infections by maintaining lower pH levels and reducing potential pathogen colonization. Dysbiosis, or imbalance of the vaginal microbial ecosystem, has been associated with both common infections, such as bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and urinary tract infections (UTIs), and obstetric complications, including gestational diabetes, preterm labor, and obstetric anemia. This review provides an overview of the composition and function of the vaginal microbiota, emphasizing the role of Lactobacillus and other beneficial microbes and their mechanisms of action, including lactic acid and hydrogen peroxide production, competitive adherence, and immune modulation. Evidence from clinical trials supports the efficacy of these strains in reducing recurrence of BV, VVC, and UTIs. Additionally, emerging research shows promise for probiotic use in managing reproductive conditions such as gestational diabetes mellitus, preterm labor, and obstetric anemia. The review also discusses safety considerations, particularly in immunocompromised individuals, and the expanding interest in non-Lactobacillus genera like Bifidobacterium and Bacillus. Targeted probiotic interventions have great potential for restoring and maintaining a healthy vaginal microbiome, preventing recurrent infections, and helping improve reproductive outcomes. However, in order to incorporate these approaches in clinical practice, probiotic strains, delivery method, and dosage all need standardization.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0001126"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338576","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

Porphyromonas gingivalis sphingolipids affect early responses of THP-1 macrophages to outer membrane vesicles. 牙龈卟啉单胞菌鞘脂影响THP-1巨噬细胞对外膜囊泡的早期反应。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-06 DOI: 10.1128/iai.00736-25

Zavier G Eure, Tamires Fernanda Vilas Boas Cordeiro, Alejandro Riveros Walker, Fernanda G Rocha, Mary Ellen Davey, Frank C Gibson

{"title":"Porphyromonas gingivalis sphingolipids affect early responses of THP-1 macrophages to outer membrane vesicles.","authors":"Zavier G Eure, Tamires Fernanda Vilas Boas Cordeiro, Alejandro Riveros Walker, Fernanda G Rocha, Mary Ellen Davey, Frank C Gibson","doi":"10.1128/iai.00736-25","DOIUrl":"10.1128/iai.00736-25","url":null,"abstract":"Porphyromonas gingivalis is an oral bacterium commonly associated with periodontitis. P. gingivalis synthesizes sphingolipids (SLs), and recently, we reported that P. gingivalis SLs packaged into outer membrane vesicles (OMVs) can regulate THP-1 macrophage inflammatory responses to P. gingivalis OMVs. The contribution that P. gingivalis SLs have on host-pathogen interactions remains poorly understood, especially in the context of OMVs. Here, we demonstrate that P. gingivalis SLs significantly reduce the uptake of OMVs isolated from SL-containing wild-type (WT) P. gingivalis compared to OMVs from an SL-null mutant P. gingivalis strain, and that the loss of SLs drives uptake of P. gingivalis OMVs via lipid rafts in THP-1 macrophages. Intriguingly, we found that the sensing of P. gingivalis OMVs via TLR2 and MyD88 is attenuated due to the presence of SLs. Lastly, transcriptomic analysis of THP-1 macrophages co-cultured with either WT or SL-null P. gingivalis OMVs for 2 h revealed an array of differentially expressed genes. Interestingly, at 2 h, WT P. gingivalis OMVs promoted an overall trend of gene downregulation in THP-1 macrophages when compared to unchallenged, whereas SL-null OMVs strongly promoted upregulated gene expression. These findings provide early-phase characterization of the role of SLs in initial host cellular responses to P. gingivalis OMVs and expand our knowledge of interactions between SL-containing P. gingivalis OMVs and the host.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0073625"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390796","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

Balancing act of cytokines in controlling the severity of Clostridioides difficile infection. 细胞因子在控制艰难梭菌感染严重程度中的平衡作用。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-17 DOI: 10.1128/iai.00551-25

Kevin S Mears, Michael C Abt

引用次数: 0

Effluxosomes and the evolution of metal resistance in Mycobacterium tuberculosis. 结核分枝杆菌外排体与金属耐药性的演变。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-06-26 DOI: 10.1128/iai.00307-26

Louis Benastre, Pierre Dupuy, Claude Gutierrez, Pascal Demange, Olivier Neyrolles

{"title":"Effluxosomes and the evolution of metal resistance in Mycobacterium tuberculosis.","authors":"Louis Benastre, Pierre Dupuy, Claude Gutierrez, Pascal Demange, Olivier Neyrolles","doi":"10.1128/iai.00307-26","DOIUrl":"10.1128/iai.00307-26","url":null,"abstract":"During infection, host immune cells deploy a variety of strategies to neutralize invading pathogens, including the manipulation of metal availability, a process traditionally understood as nutritional immunity. While depriving microbes of essential metals, such as iron and manganese, inhibits their growth, host cells also engage in metal intoxication, actively overloading phagosomes with toxic levels of transition metals, such as copper and zinc. To survive these dual pressures, Mycobacterium tuberculosis, the etiological agent of tuberculosis, has evolved specialized metal resistance mechanisms. This review explores how M. tuberculosis counters host-imposed metal stress through an arsenal of P-type ATPases, particularly the diverse P1B subfamily of transition metal exporters. We detail the structural features, metal specificities, and regulatory mechanisms of M. tuberculosis' 12 P-type ATPases, focusing on three key systems, CtpC, CtpG, and CtpV, and their cognate scaffold proteins PacL1, PacL2, and PacL3. These PacL-Ctp pairs form dynamic membrane assemblies termed effluxosomes, which mediate resistance to transition metals such as zinc and cadmium. The review also highlights several distinctive features of M. tuberculosis P1B-ATPases relative to canonical transporters such as CopA and ZntA, suggesting unique adaptations to the intracellular environment. Finally, we discuss the challenges of functionally and structurally characterizing these systems and propose future directions to elucidate effluxosome assembly and function. Together, these insights reveal how M. tuberculosis leverages metal export as a critical survival strategy and suggest novel therapeutic opportunities targeting metal detoxification pathways.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0030726"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338566","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

Pseudomonas aeruginosa infection causes lysosomal dysfunction in the cystic fibrosis bronchial epithelium. 铜绿假单胞菌感染导致囊性纤维化支气管上皮溶酶体功能障碍。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-06-30 DOI: 10.1128/iai.00347-26

Emma Lea Matthews, Meghan June Hirsch, Kuen-You Tsai, Hannah J McIntire-Ray, Viviana Acevedo Rua, Angela N Morales, Luke I Jones, Jarrod W Barnes, Megan R Kiedrowski, Stefanie Krick

{"title":"Pseudomonas aeruginosa infection causes lysosomal dysfunction in the cystic fibrosis bronchial epithelium.","authors":"Emma Lea Matthews, Meghan June Hirsch, Kuen-You Tsai, Hannah J McIntire-Ray, Viviana Acevedo Rua, Angela N Morales, Luke I Jones, Jarrod W Barnes, Megan R Kiedrowski, Stefanie Krick","doi":"10.1128/iai.00347-26","DOIUrl":"10.1128/iai.00347-26","url":null,"abstract":"Cystic fibrosis (CF) is a genetic disorder that causes chronic airway disease, leading to accelerated aging, inflammation, and susceptibility to opportunistic infections. Pseudomonas aeruginosa (PA) is prevalent in the CF lung, often multidrug-resistant, and affecting lung function decline, highlighting a need for alternative treatment strategies, such as host-directed therapeutics. The PA metabolite pyocyanin can induce senescence-associated β-galactosidase (SA-βgal), a lysosomal cell senescence marker. However, whether PA can induce cell senescence and therefore affect immune functions has not been studied. Using established airway epithelial culture models, we observed that PA infection increased SA-βgal activity and proinflammatory cytokines without increasing a comprehensive set of cell senescence markers. PA infection also resulted in lysosomal neutralization and decreased lysosome biogenesis, with the latter attenuated by rapamycin (RAPA), a senolytic and an established inhibitor of mTOR signaling. In conclusion, our study implies that PA infection does not induce cell senescence in the CF bronchial epithelium but disturbs lysosomal homeostasis, which can be attenuated by RAPA. These findings highlight lysosomal health as a promising therapeutic target in CF airways, especially as patients live longer yet remain susceptible to recurrent airway infections.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0034726"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351951","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

Pathological or preventative? Amyloid-β as an effector of innate immunity. 病理性的还是预防性的？淀粉样蛋白β作为先天免疫的效应器。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-06-26 DOI: 10.1128/iai.00085-26

Oluwagbenro O Adesunloro, Amanda N Tuckey, Jonathon P Audia, Allyson E Shea

引用次数: 0

Pseudomonas aeruginosa exotoxin A is not essential for corneal disease severity or bacterial survival. 铜绿假单胞菌外毒素A不是角膜疾病严重程度或细菌存活所必需的。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-22 DOI: 10.1128/iai.00165-26

James D Begando, Michaela E Marshall, Emma Caitlin Kundracik, George R Dubyak, Arne Rietsch, Eric Pearlman

引用次数: 0

A zoonotic Streptococcus equi subsp. zooepidemicus strain survives in activated blood neutrophils of pigs through SzM expression. 马链球菌的一种人畜共患亚种。动物流行毒株通过表达SzM在活化的猪血液中性粒细胞中存活。

IF 3.4 3区医学

Infection and Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-15 DOI: 10.1128/iai.00113-26

Sophie Öhlmann, Christine Weiße, Andreas Nerlich, Tanja Wurzer, Yannick Max Fornoville, Anna Majcher, Thomas Grochow, Simone A Fietz, Reiner Ulrich, René Bergmann, Christoph Georg Baums

{"title":"A zoonotic Streptococcus equi subsp. zooepidemicus strain survives in activated blood neutrophils of pigs through SzM expression.","authors":"Sophie Öhlmann, Christine Weiße, Andreas Nerlich, Tanja Wurzer, Yannick Max Fornoville, Anna Majcher, Thomas Grochow, Simone A Fietz, Reiner Ulrich, René Bergmann, Christoph Georg Baums","doi":"10.1128/iai.00113-26","DOIUrl":"10.1128/iai.00113-26","url":null,"abstract":"Streptococcus equi subsp. zooepidemicus (SEZ) causes diseases in various animals and humans. In pigs, it is an emerging pathogen that causes septicemia and other severe pathologies. SEZ expresses the M-like protein SzM, which recruits host proteins such as fibrinogen to the bacterial surface. The objective of this study was to investigate the survival mechanism of a zoonotic SEZ strain in porcine blood. The zoonotic SEZ C33 strain proliferated in porcine blood of 10-week-old piglets in vitro despite comparably high levels of IgM binding to the bacterial surface. Comparison with the isogenic szm deletion mutant showed that SzM_C33 expression is crucial for porcine blood survival. Flow cytometry analysis revealed that SEZ C33 was associated with porcine blood granulocytes, exhibiting a prominent generation of reactive oxygen species. Cytochalasin D treatment significantly inhibited this association. Furthermore, we found viable intracellular SEZ C33 in a penicillin/streptomycin protection assay in porcine blood and purified porcine granulocytes, in agreement with the microscopic detection of streptococci in neutrophils. Experimental infection with SEZ C33 confirmed the virulence of this strain in pigs, including one case of fibrino-suppurative meningoencephalitis and tarsitis. In conclusion, SEZ C33, originally isolated from a diseased human, demonstrated SzM-mediated intracellular survival in porcine blood granulocytes in vitro and is most likely involved in the pathogenesis of diseases such as meningitis and arthritis in vivo.","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0011326"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446011","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