Infection and Immunity最新文献

{"title":"Gut microbial metabolism of amino acids and its impact on enteric infections.","authors":"Kanchan Jaswal, Judith Behnsen","doi":"10.1128/iai.00298-26","DOIUrl":"https://doi.org/10.1128/iai.00298-26","url":null,"abstract":"<p><p>Amino acids are the fundamental building blocks of proteins. Dietary proteins and endogenous protein turnover are the main sources of amino acids in the body. Over the past decade, our understanding of the role of the gut microbiota in amino acid metabolism has expanded considerably. The gut microbiota metabolizes dietary amino acids, regulates intestinal amino acid bioavailability, and maintains host nutrient homeostasis. Besides nutrient regulation, emerging evidence has revealed that amino acid availability in the gut also plays a crucial role in modulating enteric infections. Amino acids can influence infection outcomes both directly, by affecting the virulence of enteric pathogens, and indirectly, by shaping host immune responses. While most studies have focused on bacterial metabolism of amino acids, recent findings highlight important contributions from non-bacterial members of the gut microbiota, including fungi and protists. Both fungi and protists can shape amino acid availability in the gut and, consequently, infection outcomes. In this review, we integrate current knowledge on how diet and amino acid metabolism, mediated by both bacterial and non-bacterial communities, collectively influence enteric infection dynamics.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0029826"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136510","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}

{"title":"Self-destructing attenuated adjuvant <i>Salmonella</i> strains: design, construction, characterization, and evaluation of safety and efficacy following <i>in ovo</i> inoculation of chicken embryos.","authors":"Vinicius Lima, Douglas Natoce, Soo-Young Wanda, Shifeng Wang, Banikalyan Swain, Roy Curtiss","doi":"10.1128/iai.00318-26","DOIUrl":"https://doi.org/10.1128/iai.00318-26","url":null,"abstract":"<p><p>Self-destructing attenuated adjuvant <i>Salmonella</i> (SDAAS) strains are next-generation attenuated <i>S</i>. Typhimurium strains designed to be used as live adjuvants. They possess diverse means to prevent persistence <i>in vivo</i>, survival if excreted, and to enhance the induction of innate immunity. In this study, we investigated whether SDAAS strains can be safely delivered to chicken embryos by <i>in ovo</i> inoculation without compromising hatchability or hatchling health. We then evaluated their growth in different media, sensitivity to complement-mediated killing, motility, serum agglutination, flagellar and LPS profiling, their ability to attach to and invade Int-407 cells, and the activation of different pattern recognition receptors displayed by HEK-Blue cells. We also determined whether these strains could induce protective immune responses in chicks following homologous challenge at day of hatch with a virulent <i>S</i>. Typhimurium strain by reducing intestinal colonization and organ invasion. Our findings demonstrate that SDAAS strains can be safely administered <i>in ovo</i> in a dose-dependent manner. Family A strains exhibit strict requirements for 2,6-diaminopimelic acid and D-alanine, while Family B strains demonstrate absolute dependence on L-arabinose for growth in liquid and solid media. Adjuvant strains demonstrate increased activation of murine receptors NOD1, NOD2, TLR4, TLR5, TLR8, and TLR9 in HEK-Blue cells compared to the parent strain χ3761, despite having lower rates of cell adhesion to and invasion of Int-407 cells. Lastly, we observed that <i>in ovo</i> administration of SDAAS strains reduced titers of <i>S</i>. Typhimurium recovered from birds as they became older, suggesting a time-dependent enhancement of protective immunity induced by SDAAS strains.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0031826"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136465","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}

{"title":"Immune responses induced by a subunit vaccine against <i>Mycoplasma gallisepticum</i>.","authors":"Jeremy M Miller, Arlind B Mara, Rosemary G Ozyck, Richard Savoie, Esmeralda F Hernandez, Kyunghyun Lee, Morgan L Hunte, Jessica B Malek, Edan R Tulman, Steven M Szczepanek, Steven J Geary","doi":"10.1128/iai.00305-26","DOIUrl":"https://doi.org/10.1128/iai.00305-26","url":null,"abstract":"<p><p><i>Mycoplasma gallisepticum</i> (MG) is an avian respiratory pathogen responsible for global economic loss to the poultry industry. We previously developed an efficacious subunit vaccine to address the drawbacks of current bacterin and live-attenuated vaccine designs. To improve our understanding of how the subunit vaccine works, we sought to understand if the vaccine influences the biology of the pathogen, whether the subunit vaccine has correlates of protection when analyzing antibody responses or tracheal-associated cells, and whether each component of the subunit vaccine contributes to protection. We performed five experiments to answer these questions. In the first experiment, we found that the subunit vaccine induces changes in the <i>in vivo vlhA</i> expression patterns of the infecting MG. We also found that on day 1 post-challenge, anti-VlhA 3.06 systemic IgY correlated negatively with the thickest tracheal mucosal section. In the second experiment, we found that on day 1 post-challenge, anti-MG lysate systemic IgY, anti-VlhA 3.03 systemic IgY, and anti-VlhA 5.05 systemic IgY negatively correlated with bacterial recovery. We also found that when looking at tracheal-associated cell frequencies, γδ T cells, with specific regard to CD8^- γδ T cells, and monocytes/macrophages, with specific regard to the monocyte/macrophage:granulocyte ratio, were negatively correlated with bacterial recovery, average tracheal mucosal thickness, or thickest tracheal mucosal section. In experiments three through five, we found that VlhAs 3.03, 3.06, and 5.05 contributed to reducing bacterial recovery, whereas VlhA 4.07 was dispensable, and we found that GapA and CrmA contributed to reducing bacterial recovery and average tracheal mucosal thickness.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0030526"},"PeriodicalIF":3.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127413","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}

{"title":"Metabolic modeling: the link between AI and multi-omics data to accelerate the discovery of antibiotic-resistant traits in ESKAPE pathogens.","authors":"Nazmul Muzahid, Arjun Patel, Mason Raymond, Tiana Egidi, Nhi Nguyen, Cristal Zuniga","doi":"10.1128/iai.00435-26","DOIUrl":"https://doi.org/10.1128/iai.00435-26","url":null,"abstract":"<p><p>The development of predictive understanding of bacterial resistance to antibiotics is one of the greatest challenges of modern medicine. Genome-scale metabolic models (GEMs) are mathematical representations of the metabolic network of a given organism assembled from genomic data that predict cellular activity across many environmental and genetic contexts. Because a single model can be solved under thousands of conditions, GEMs generate data at scales that support downstream analysis with artificial intelligence tools, helping to elucidate how pathogens adapt to host environments, evade immune responses, and acquire resistance. Here, we review how GEMs of ESKAPE pathogens are built, what data they require, and what they can and cannot do. We describe the reconstruction workflow from automated draft network through manual curation, gap filling, and experimental validation and the public and experimental data sources each stage depends on. We then describe how accessory genes and transcriptomic measurements are incorporated to yield strain- and condition-specific models and where machine learning contributes both in expanding functional annotation and in consuming model-generated flux distributions. Applications are illustrated with ESKAPE examples throughout, including conserved metabolic vulnerabilities identified across strain collections and flux rewiring observed under antibiotic exposure. Despite this progress, high-quality GEMs exist for only a fraction of ESKAPE species; many are constrained by incomplete annotation or limited experimental validation, and non-metabolic resistance mechanisms are captured only insofar as they impose a metabolic cost. Providing reliable tools to build new models from trustworthy templates, therefore, remains a priority for narrowing the gap between genotype and phenotype.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0043526"},"PeriodicalIF":3.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127422","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}

{"title":"Tumor necrosis factor-α coordinates the macrophage innate immune response to <i>Histoplasma capsulatum</i>.","authors":"Bradford L Crowther, William Buesing, Ty Troutman, George S Deepe","doi":"10.1128/iai.00302-26","DOIUrl":"https://doi.org/10.1128/iai.00302-26","url":null,"abstract":"<p><p><i>Histoplasma capsulatum</i> is a fungal pathogen that thrives in macrophages until activated by interferon-gamma (IFN-γ). Tumor necrosis factor-α (TNF-α) is required for control of infection during adaptive immunity but does not directly activate macrophages to eliminate fungal elements. Collapse of immunity associated with TNF-α blockade is not accompanied by depression of IFN-γ. To determine if TNF-α antagonism impairs fungal clearance prior to adaptive immunity, we infected mice given anti-TNF-α and quantified lung <i>H. capsulatum</i> up to day 3 of infection. Anti-TNF-α elevated the number of organisms in the lungs by day 3. Neutralization of IFN-γ manifested a similar effect. Since neutralization of both cytokines impaired innate immunity, we hypothesized that the action of IFN-γ required TNF-α. IFN-γ-stimulated macrophages expressed fungicidal activity <i>in vitro</i>, and TNF-α neutralization or its congenital deficiency in macrophages reversed this effect. Blockade of TNF-α slightly dampened M1 response but did not promote M2. TNF-α was not required for IFN-γ to shift the metabolic capacity of macrophages. We investigated the production of nitric oxide, which is a mediator of anti-<i>H</i>. <i>capsulatum</i> activity by macrophages. In the absence of TNF-α, there was no difference when compared to IFN-γ stimulation alone. Lung macrophages harbored the highest infection burden in anti-TNF-α recipients. Though IFN-γ receptor 1 was modestly downregulated by anti-TNF-α blockade, this treatment downregulated pSTAT1 at day 2 of infection. TNF-α is required for optimal IFN-γ signaling and effector function of cytokine-stimulated macrophages. When TNF-α is absent, macrophages are insufficiently activated and fail to halt intracellular growth of yeast cells.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0030226"},"PeriodicalIF":3.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080722","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}

{"title":"Curiouser and curiouser: understanding the intersection of inter- and intra-specific diversity during the <i>Borrelia burgdorferi</i> enzootic cycle and Lyme disease.","authors":"Marina S Winter, Kareem D Adams, Jeffrey S Bourgeois","doi":"10.1128/iai.00554-25","DOIUrl":"10.1128/iai.00554-25","url":null,"abstract":"<p><p>A consequence of the <i>Borrelia</i> (<i>Borreliella</i>) <i>burgdorferi</i> lifecycle is that a \"standard\" host-pathogen interaction involving the spirochete is challenging to define. The bacteria continuously cycle between vertebrate and invertebrate hosts, each inflicting substantially different selective pressures on the spirochete. Focusing solely on vertebrate infections, the spirochete can be found in numerous hosts in nature, including deermice, shrews, birds, and lizards. The immune pressures that the bacteria face in each of these hosts are variable and are thought to drive broad intraspecific variation across <i>B. burgdorferi</i> strains-with different strains appearing to be avian adapted, mammalian adapted, or generalist. In addition to its natural zoonotic hosts, <i>B. burgdorferi</i> can infect humans and cause Lyme disease. Here, natural human genetic variation can drive dramatically different disease outcomes, as some individuals seem capable of killing the bacteria before it can successfully colonize, while others are predisposed to continue reacting to the pathogen even long after it is killed by antibiotics. In this review, we describe studies investigating how host and bacterial diversity affect <i>B. burgdorferi</i> infection outcomes, with an emphasis on how this variability impacts the bacteria's spread in nature and Lyme disease severity during human infection.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0055425"},"PeriodicalIF":3.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669374","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}

{"title":"Comparison of <i>Galleria mellonella</i>, epithelial cell cytotoxicity, and mouse model of bacteremia to measure <i>Pseudomonas aeruginosa</i> virulence.","authors":"Aliki Valdes, Christopher Axline, Travis J Kochan, Sophia Nozick, Timothy Ward, Issay Niki, Ethan VanGosen, David Hynes, Julia Nelson, Preeti Garai, Tania Afzal, Daniel Amusin, Sumitra D Mitra, Timothy L Turner, William Cheng, Joanne J Lee, Prarthana Prashanth, Nathan B Pincus, Jonathan P Allen, Jake Hauser, Egon A Ozer, Kelly E R Bachta, Cheng-Hsun Chiu, Antonio Oliver, Alan R Hauser","doi":"10.1128/iai.00335-26","DOIUrl":"10.1128/iai.00335-26","url":null,"abstract":"<p><p>Considerable effort has focused on identifying alternatives to mouse models in research studies. In the field of bacterial pathogenesis, <i>Galleria mellonella</i> and epithelial cell lines have been widely used for this purpose, but the concordance of these models with mice remains unclear. To begin to address this knowledge gap, we used 105 clinical isolates of <i>Pseudomonas aeruginosa</i> for which virulence had previously been determined in a mouse bacteremia model. A semistrong correlation was observed between <i>G. mellonella</i> median time to 50% mortality and mouse 50% pre-lethal dose (LD₅₀) values (Spearman's rank correlation coefficient [ρ] = 0.75), whereas percent A549 epithelial-like cell lysis during co-culture showed a weak correlation to mouse LD₅₀ values (ρ=-0.47). Given the stronger correlation between <i>G. mellonella</i> and mouse virulence, we next examined whether <i>G. mellonella</i> could substitute for mice when asking questions about the virulence of large numbers of <i>P. aeruginosa</i> isolates. Results from mice indicated that isolates with resistance to more antibiotics were significantly less virulent, and the use of <i>G. mellonella</i> identified the same inverse correlation. Furthermore, both models found no evidence for the existence of hypervirulent clonal lineages. In particular, isolates belonging to sequence types defined as high-risk clones were not consistently more virulent than other isolates, despite the known association of high-risk clones with poor clinical outcomes. These findings suggest that <i>G. mellonella</i> can serve as an adequate substitute for mice when addressing specific population-based virulence questions, although conclusions should be confirmed in mice.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0033526"},"PeriodicalIF":3.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792579","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}

{"title":"Dual roles of genes required for intrinsic resistance to clarithromycin in evasion of killing by serum complement in <i>Haemophilus influenzae</i>.","authors":"Cameron Huhn, Justine Dees, Jeffrey Gawronski, Asma Ul Taslim, Sandy Wong, Brian Akerley","doi":"10.1128/iai.00369-26","DOIUrl":"10.1128/iai.00369-26","url":null,"abstract":"<p><p>Macrolide antibiotics are commonly prescribed to treat <i>Haemophilus influenzae</i> respiratory tract infections. Studies have primarily focused on emerging <i>H. influenzae</i> strains with acquired macrolide resistance, while the bacterium's intrinsic resistance to antibiotics has been underexamined. Here, we used a genome-wide approach of transposon insertion-site sequencing to screen an <i>H. influenzae</i> mutant library grown in sub-inhibitory doses of the macrolide antibiotic clarithromycin (CLR) to identify 33 genes involved in intrinsic CLR resistance. Almost half of these genes are also needed for survival in the mouse lung. We focused on candidate genes necessary for both intrinsic macrolide resistance and lung survival. Two of these genes affect the outer-membrane composition of <i>H. influenzae</i>, <i>orfH</i> and <i>omp26</i>. Deletions of these genes in Rd and nontypeable <i>H. influenzae</i> clinical isolates, Hi375 and NT127, conferred sensitivity to CLR and polymyxin B and increased membrane permeability to ethidium bromide (EtBr). The <i>omp26</i> mutant was sensitive to killing by human serum. Deletions of <i>orfH</i> or <i>omp26</i> in an <i>acrR</i> mutant strain overexpressing a multidrug efflux pump abrogated resistance of the <i>acrR</i> mutant to CLR and restored permeability to EtBr. Thus, deletion of these genes not only mitigates the effects of an acquired resistance mechanism but also remarkably overrides it. Complementation of these deletion mutations restored CLR resistance and decreased permeability to EtBr. Our results indicate that the subset of genes with dual roles in intrinsic resistance and host lung survival may provide potential novel combination antimicrobial therapeutic targets.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0036926"},"PeriodicalIF":3.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678321","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}

{"title":"The AP-1 adaptor complex is required for cell surface modifications and the survival of <i>Cryptococcus neoformans</i> in phagocytic cells.","authors":"Eddy Sánchez-León, Kabir Bhalla, Victoria French, Polina Beskrovnaya, Shweta Parmar, Guanggan Hu, Melissa Lagace, Sophie Thanasack, E Johan Foster, Elitza I Tocheva, James W Kronstad","doi":"10.1128/iai.00098-26","DOIUrl":"10.1128/iai.00098-26","url":null,"abstract":"<p><p>The pathogenic yeast <i>Cryptococcus neoformans</i> causes life-threatening meningoencephalitis in individuals with compromised immune systems. The ability of the fungus to cause disease depends on key cell-surface features, such as a polysaccharide capsule that protects it from the mammalian immune system. However, the mechanisms by which <i>C. neoformans</i> traffics polysaccharide capsule, melanin, and other materials to the cell surface are poorly understood. In this study, we employed mutants lacking specific subunits of the adaptor protein complex 1 (AP-1) to investigate its role in the elaboration of virulence-related materials at the cell surface. Importantly, the mutants displayed multiple defects, including alterations in capsule size and cell morphology, and defects in melanin production and urease secretion. Together, these results support the key observation that the AP-1 complex is required for <i>C. neoformans</i> survival in phagocytic cells. Together, our findings provide insights into the endomembrane trafficking machinery required for fungal pathogenesis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0009826"},"PeriodicalIF":3.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669392","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}

{"title":"HDAC6 inhibition reduces <i>Pseudomonas aeruginosa</i> 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":"10.1128/iai.00225-25","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i>. 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.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0022525"},"PeriodicalIF":3.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552101/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}