Microbial pathogenesis最新文献

{"title":"Preparation of steam explosion modified pea protein peptides and its antibacterial mechanism against Staphylococcus aureus.","authors":"Yanqing Zhang, Mingwu Qiao, Yue Shen, Ning Li, Xianqing Huang, Fengmei Lei, Junxiao Hei, Qian Li, Lianjun Song","doi":"10.1016/j.micpath.2026.108882","DOIUrl":"https://doi.org/10.1016/j.micpath.2026.108882","url":null,"abstract":"<p><p>In this study, the enzymatic hydrolysis process of steam explosion modified pea proteins was optimized through single-factor experiments and a Box-Behnken experimental design. The maximum degree of hydrolysis of 23.13% was achieved at 7.38% substrate concentration (w/v), 5% enzyme-to-substrate ratio (w/w), pH 9.5, and 55 °C for 3 h. Steam explosion modified pea protein peptides (SE-PPP) exhibited strong antibacterial activity against Staphylococcus aureus (S. aureus), with a minimum inhibitory concentration of 0.0244 mg/mL. Mechanistic studies revealed that SE-PPP disrupted the integrity of bacterial cell wall and membrane, as evidenced by increased alkaline phosphatase activity, decreased adenosine triphosphate levels, reactive oxygen species and malondialdehyde accumulation. These effects led to nucleic acid and protein leakage, thereby inhibiting bacterial proliferation. These findings confirmed that steam explosion pretreatment markedly enhanced the yield of low-molecular-weight peptides from pea protein. Moreover, the obtained SE-PPP had excellent antibacterial activity against S. aureus, supporting its potential as a natural food preservative for the high-value utilization of pea proteins.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108882"},"PeriodicalIF":3.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228339","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":"The key amino acids (cysteine and histidine) across BVDV-1 N^pro sequence that affect autoprotease activity and inhibition of IFN-β synthesis.","authors":"Xiao-Ting Ren, Ju-Shuang Hong, Le-le An, Tong Wang, Xiao-Xia Ma","doi":"10.1016/j.micpath.2026.108891","DOIUrl":"https://doi.org/10.1016/j.micpath.2026.108891","url":null,"abstract":"<p><p>The N-terminal protease (N^pro) of bovine viral diarrhea virus (BVDV) possesses two major biological functions, namely autoprotease activity and antagonism of interferon (IFN) synthesis, both of which are important for viral replication and immune evasion. Given the high mutation rate of the BVDV genome, whether mutations in N^pro affect these functions remains largely unknown. Because cysteine and histidine residues are critical determinants of N^pro activity, we systematically investigated the roles of all cysteine and histidine residues in regulating autoprotease activity and IFN antagonism. Synonymous codon substitutions involving cysteine or histidine residues did not affect the autoprotease activity of N^pro. In contrast, analyses of nonsynonymous substitutions revealed that, in addition to the previously identified catalytic residues His49 and Cys69, His40, His99, and the zinc-binding residues Cys112, Cys134, and Cys138 were also essential for efficient autoprotease activity. By comparison, substitution of His148 had no detectable effect on either autoprotease activity or IFN antagonism. Functional dissociation analyses demonstrated that mutations at Glu22 and His49 enhanced IFN-β antagonism while abolishing autoprotease activity, whereas the Cys69 mutation abolished autocleavage but retained IFN suppression. In contrast, certain substitutions at His130 and Cys161 selectively impaired IFN antagonism without affecting autocleavage, indicating that these two functions are partially separable. Notably, mutations at His40, His99, Cys112, Cys134 and Cys138 markedly impaired both autoprotease activity and IFN antagonism, suggesting that these residues represent common functional determinants of the two activities. Sequence alignment of N^pro proteins from different BVDV-1 strains identified naturally occurring non-conservative variations at positions 40, 130 and 148. Further analyses showed that the naturally occurring His40Arg and His130Pro substitutions significantly affected both autoprotease activity and IFN antagonism, supporting a functional association between N^pro autocleavage and IFN suppression. In contrast, His148Arg, His148Asn, and His148Gln substitutions had no detectable effect on either activity. Collectively, these findings demonstrate that cysteine and histidine residues play critical roles in regulating both autoprotease activity and IFN antagonism of BVDV-1 N^pro. Mutations at specific residues differentially affect these functions, highlighting the importance of conserved cysteine and histidine residues in maintaining the multifunctional properties of N^pro.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108891"},"PeriodicalIF":3.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228334","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":"Therapeutic effects of Stemona japonica extract against Mycoplasma gallisepticum infection: Association with suppression of NF-κB-mediated inflammatory response.","authors":"Wei Yao, Xicai Liang, Zehui Zhang, Xueyu Li, Xinrui Ma, Zelin Zhao, Zhenqi Wu","doi":"10.1016/j.micpath.2026.108890","DOIUrl":"10.1016/j.micpath.2026.108890","url":null,"abstract":"<p><p>Mycoplasma gallisepticum (MG) is the primary causative agent of chronic respiratory disease (CRD) in chickens, causing massive economic losses to the global poultry industry. The widespread emergence of antibiotic-resistant MG strains has created an urgent need for safe and effective alternative therapies. Stemona japonica (Baibu), a traditional Chinese medicine with well-documented antitussive and anti-inflammatory properties, has not been systematically evaluated for its anti-MG activity. This study investigated the therapeutic effects of S. japonica extract against MG infection both in vitro and in vivo, and elucidated its underlying molecular mechanisms. In chicken respiratory epithelial cells, S. japonica extract significantly alleviated MG-induced cellular injury, improved cell viability, reduced apoptosis, and dose-dependently downregulated the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ). Mechanistically, S. japonica suppressed MG-induced activation of the NF-κB signaling pathway by inhibiting the phosphorylation and degradation of IκBα and subsequent phosphorylation of p65. In a chicken MG infection model, S. japonica treatment significantly alleviated clinical symptoms, reduced body weight loss and mortality, elevated serum IgG and IgA levels, and attenuated lung pathological damage. Transcriptome sequencing further confirmed that S. japonica reversed MG-induced gene expression changes, with differentially expressed genes highly enriched in NF-κB, TNF, and cytokine-receptor interaction pathways. Collectively, these findings demonstrate that S. japonica exerts potent therapeutic effects against MG infection, which is associated with suppression of NF-κB-mediated inflammatory responses and enhancement of host humoral immunity. This study provides a scientific basis for the development of S. japonica as a promising alternative agent for the treatment of CRD in poultry.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108890"},"PeriodicalIF":3.9,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224448","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":"Salmonella phage characterization and host-dependent responses relevant to cocktail formulation.","authors":"Yuechong Liu, Xi Liu, Song Zhang, Juhee Ahn","doi":"10.1016/j.micpath.2026.108883","DOIUrl":"https://doi.org/10.1016/j.micpath.2026.108883","url":null,"abstract":"<p><p>This study was characterized infection efficiency, replication kinetics, environmental tolerance, and host-associated responses of six Salmonella phages (Yrd1, Yrd2, NB1, NB2, NB3, and FPU) as candidate parameters relevant to cocktail formulation. All phages belong to the class Caudoviricetes, comprising five myovirus-like and one siphovirus-like (NB3) morphotype, with capsid dimensions of 38-74 nm in width and 46-94 nm in length, and tail lengths of 78-109 nm. Multiplicity of infection (MOI) assays (0.001-10) showed that low MOI conditions (0.001-0.01) produced higher phage amplification, whereas a high MOI (10) markedly reduced amplification, indicating reduced infection efficiency at higher phage-to-host ratios. One-step growth analysis (MOI 0.1) showed phage-specific latent periods ranging from 10 to 30 min. Burst size ranged from 15 to 389 PFU/cell, with Yrd2 and NB1 showing the two highest values. Stability assays showed phage-specific responses. FPU displayed the broadest pH tolerance profile in the plotted comparison, retaining normalized infectivity from pH 5 to 10, and showed the highest plotted normalized infectivity at 50-60^OC. All six phages showed near-zero normalized infectivity at pH 2-3, pH 11-12, and 70^OC. Network-based interaction analysis showed broader OD-based inhibitory connectivity for selected cocktails than for monophages across PU13036, EN, KE, and TY. On PU519, specific FPU-containing combinations showed reduced inhibition, but these effects are not interpreted as mechanistic phage-phage antagonism or generalized beyond the tested host. Because the assays used different host backgrounds, these measurements provide candidate parameters for future cocktail-selection studies, but their predictive value requires further validation.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"221 ","pages":"108883"},"PeriodicalIF":3.9,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224510","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":"Molecular identification and pathogenicity study of Pseudomonas juntendi isolated from infected Nile tilapia.","authors":"Kampan Bisai, Aswathy Ashokan, Chinmaya Kumar Parida, Pragati Shetty, Perumal Muthuvinayagam, Kanchi Bhargavi, Sophia Margaret Joseph, Sudalayandi Kannappan, Bijay Kumar Behera","doi":"10.1016/j.micpath.2026.108885","DOIUrl":"10.1016/j.micpath.2026.108885","url":null,"abstract":"<p><p>Bacterial pathogens are major threats to sustainable aquaculture, leading to huge economic losses and reducing fish health and productivity. In this study, isolation, identification and characterization of the causative agent of acute mortality (approximately 55%) in Nile tilapia (Oreochromis niloticus) was carried out. The isolate was identified as Pseudomonas juntendi based on multilocus sequence analysis (16S rRNA, gyrB, rpoB and rpoD), showing highest similarity to reference strains. Most of the biochemical features were in line with previously reported P. juntendi. Virulence factors of the bacterium included high swimming motility, efficient biofilm formation and β-hemolysis. Antibiogram assay indicated that the isolate was resistant to six types of antibiotics with a calculated MAR index of 0.25. Pathogenicity was confirmed experimentally after challenge of healthy Nile tilapia fingerlings, resulting in development of hemorrhagic lesions and mortality with 96 h median lethal dose (LD₅₀) of 5.9 × 10⁵ CFU/fish. Sublethal infection significantly altered host-response gene expression in liver and head kidney tissues, marked by upregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), immune-related transcription factors (NF-κB and TLR-7), the chemotactic mediator CC-chemokine 1 and the antigen-presentation marker MHC-IIα. Histopathological examination revealed extensive tissue damage in the liver and head kidney with cellular degeneration, aggregation and structural disorganization, indicating systemic infection. The findings in this study clearly demonstrate for the first time that P. juntendi is a virulent pathogen in Nile tilapia, causing significant mortality, tissue damage and immune responses. This investigation contributes to our growing understanding of bacterial pathogens in tilapia farming.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108885"},"PeriodicalIF":3.9,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207256","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":"Quorum sensing and quenching as integrated strategies for antimicrobial resistance mitigation in aquaculture: Applications and future directions.","authors":"Arielle Shelby, Nitish Kumar Sankurabhukta, Grace Ramena, Susan Knudson, Yathish Ramena","doi":"10.1016/j.micpath.2026.108884","DOIUrl":"10.1016/j.micpath.2026.108884","url":null,"abstract":"<p><p>The rapid expansion of aquaculture has been accompanied by an increased prevalence of bacterial diseases, leading to widespread antibiotic use and the accelerated emergence of antimicrobial resistance (AMR). Rising water temperatures and environmental stressors further exacerbate pathogen proliferation and disease outbreaks, posing significant threats to global aquaculture productivity and sustainability. Quorum sensing (QS), a bacterial cell-to-cell communication system, plays a central role in regulating virulence factor expression, biofilm formation, and AMR-related pathways in aquatic pathogens. Consequently, disrupting QS through quorum quenching (QQ) has emerged as a promising alternative to conventional antibiotic-based treatments. This review synthesizes current knowledge on the mechanisms underlying QS and its role in AMR development in aquaculture systems. It highlights various QQ strategies, including enzymatic degradation of signaling molecules, competitive inhibition using small-molecule quorum sensing inhibitors, and the application of probiotic organisms capable of interfering with QS pathways. Evidence from recent studies demonstrates that QQ can effectively reduce virulence, enhance antibiotic sensitivity, and lower the required dosage of antimicrobial agents. Despite its potential, the implementation of QQ in aquaculture faces several challenges, including environmental stability, scalability, species-specific variability in QS systems, and regulatory concerns. Future research should focus on developing broad-spectrum, non-toxic, and environmentally stable QQ agents, as well as improving delivery systems for practical field applications. Overall, quorum quenching represents a promising, eco-friendly strategy to mitigate AMR, reduce antibiotic dependence, and enhance the sustainability of aquaculture systems worldwide.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108884"},"PeriodicalIF":3.9,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216542","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":"Biofilm-mediated pathogenesis in staphylococcal bovine mastitis: A mechanistic review of virulence, pharmacokinetic barriers, and advanced anti-biofilm therapeutic strategies.","authors":"Hemanth Kumar Lakhanapuram, Kunchaphorn Ratchasong, Avinash Varma, Vijay Kumar, Muhammad Arslan, Phirabhat Saengsawang, Watcharapong Mitsuwan","doi":"10.1016/j.micpath.2026.108880","DOIUrl":"10.1016/j.micpath.2026.108880","url":null,"abstract":"<p><p>Bovine mastitis remains one of the most economically significant infectious diseases affecting dairy production worldwide, causing substantial losses through reduced milk yield, treatment costs, and premature culling. Among the causative agents, Staphylococcus aureus and non-aureus staphylococci (NAS) are particularly problematic due to their capacity to establish chronic intramammary infections through biofilm formation, facilitating immune evasion and marked antimicrobial tolerance. Following PRISMA 2020 guidelines, this systematic review integrates mechanistic and translational evidence on biofilm-mediated pathogenesis, pharmacokinetic barriers, and anti-biofilm interventions in staphylococcal bovine mastitis. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science Core Collection was conducted for investigations published between January 2015 and February 2026. From 513 identified records, 26 primary empirical studies met all eligibility criteria and were synthesized. Mechanistically, staphylococcal biofilm development entails initial adhesion mediated by microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), followed by extracellular matrix accumulation governed by the icaADBC operon responsible for polysaccharide intercellular adhesin (PIA/PNAG) synthesis, alongside ica-independent pathways orchestrated by the biofilm-associated protein (Bap) and extracellular DNA (eDNA). These developmental stages and dispersal dynamics are coordinated by the agr quorum-sensing system and the global regulator sarA. Comparative genomic evidence indicates that NAS species, particularly Staphylococcus chromogenes and Staphylococcus haemolyticus, harbor specialized virulence and antimicrobial resistance determinants that drive subclinical persistence. Beyond bacterial determinants, antimicrobial efficacy is severely constrained by mammary pharmacokinetic barriers, including non-specific drug binding to milk proteins, sequestration in fat globules, and rapid clearance during milking cycles. Emerging therapeutic strategies notably phytochemical-loaded nanoemulsions, matrix-dispersing enzymes, and bacteriophage endolysins-demonstrate substantial capacity to dismantle established biofilms and restore antimicrobial susceptibility in preclinical models. Overcoming persistent staphylococcal mastitis will require translating dual-action formulations combining matrix-degrading agents with advanced delivery systems into validated intramammary therapeutics.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108880"},"PeriodicalIF":3.9,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216540","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":"Identification of atypical Escherichia coli as hidden reservoir of tet(X4)-positive IncX1 plasmid.","authors":"Jie Zhang, Ke Wu, Mengjiao Du, Di Xie, Ling Xu, Honglin Peng, Yi Zhou, Changwei Lei, Hongning Wang, Xin Yang","doi":"10.1016/j.micpath.2026.108886","DOIUrl":"10.1016/j.micpath.2026.108886","url":null,"abstract":"<p><p>The horizontal dissemination of antimicrobial resistance genes (ARGs) poses a significant threat to public health. In this study, we investigated the presence and transferability of a tet(X4)-positive IncX1 plasmid in an atypical Escherichia coli isolate, GX-3-49. Genomic analysis revealed that GX-3-49 is markedly distinct from conventional E. coli, characterized by a reduced gene repertoire, fewer toxin genes, and a distinct phylogenetic lineage. Phenotypic characterization further demonstrated that, compared to the reference strain EC25922, GX-3-49 exhibits diminished motility, growth, and virulence, alongside a marked increase in biofilm formation and pH tolerance, but greater sensitivity to high temperature. These findings suggested that GX-3-49 might have evolved a fitness trade-off, reducing its virulence in exchange for enhanced resilience under acidic and biofilm-forming conditions. Additionally, a tet(X4)-positive IncX1 plasmid co-harboring bla_SHV-12, tet(A), and floR, was identified in GX-3-49 and remained stable during serial passaging. This plasmid exhibited high sequence similarity to IncX1 plasmids previously identified in E. coli and Klebsiella pneumoniae and was capable of conjugative transfer to E. coli EC600, suggesting its potential for interspecies dissemination. In conclusion, this study identified a stable and transferable tet(X4)-positive IncX1 plasmid in an atypical E. coli strain exhibiting reduced virulence and increased susceptibility to heat, yet enhanced stress resilience under specific environmental conditions. These findings highlight the potential of such bacteria to serve as hidden reservoirs for antimicrobial resistance and facilitate the dissemination of ARGs.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108886"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207176","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":"Molecular epidemiology of NDM-producing Enterobacterales in Huai'an, China: Genomic diversity and evaluation of aztreonam-avibactam and cefiderocol.","authors":"Ping Chen, Haifeng Yang, Jingchen Hao, Guangyu Bao, Huachun Jiang, Jian Hu, Chengfeng Gao, Jun Xie, Guocai Li","doi":"10.1016/j.micpath.2026.108887","DOIUrl":"10.1016/j.micpath.2026.108887","url":null,"abstract":"<p><p>Metallo-β-lactamase-producing carbapenem-resistant Enterobacterales (MBL-CRE) pose a serious threat due to antimicrobial resistance. However, their prevalence in the Huai'an region of Jiangsu Province in eastern China remains unknown. Carbapenem-resistant Enterobacterales (CRE) isolates collected from Xuyi People's Hospital were screened for carbapenemase production using the modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM), followed by PCR confirmation. Antimicrobial susceptibility testing, biofilm formation assays, growth kinetics analyses, and whole-genome sequencing with bioinformatics were performed to characterize the isolates. The 12 NDM-producing Enterobacterales identified comprised seven Escherichia coli, three Klebsiella pneumoniae, and two Enterobacter hormaechei. Beyond carbapenem resistance, resistance to aztreonam, tetracycline, fluoroquinolones, and aminoglycosides was common among the isolates. Four isolates (including three E. coli) showed intermediate susceptibility to cefiderocol, and the aztreonam-avibactam combination exhibited synergistic activity against aztreonam-resistant NDM-producing isolates. Genomic analysis revealed eight isolates carrying bla_NDM-5, three carrying bla_NDM-1, and one carrying bla_NDM-13. These isolates belonged to various sequence types, including two novel types. The NDM-13 isolate and one NDM-1-positive E. hormaechei isolate displayed distinct genetic contexts, whereas most isolates harbored a bla_NDM-ble_MBL-trpF-tat-dct genetic structure. Among the three cefiderocol-intermediate E. coli isolates, mutations were identified in cirA and ftsI. This study reveals the prevalence and diverse genetic backgrounds of MBL-CRE in Xuyi County, demonstrates the potent activity of aztreonam-avibactam, and suggests that cefiderocol resistance may involve multiple factors.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108887"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207225","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":"PA4933 mediates dual regulation of oxidative resistance and virulence in Pseudomonas aeruginosa pulmonary infection.","authors":"Haining Xia, Yinzhen Liu, Yangcheng Shen, Ronghua Zhong, Shebin Zhang, Jieying Pu, Cong Shen, Cha Chen, Jianming Zeng","doi":"10.1016/j.micpath.2026.108878","DOIUrl":"10.1016/j.micpath.2026.108878","url":null,"abstract":"<p><p>Pseudomonas aeruginosa is a critical opportunistic pathogen requiring rigorous prevention and control, which triggers severe infections in immunocompromised populations. Bacterial membrane proteins serve as core regulatory molecules coordinating stress tolerance and virulence homeostasis during host colonization. Nevertheless, the physiological functions of numerous structurally homologous yet unannotated membrane proteins remain largely elusive. In this study, we identified a significantly upregulated hypothetical gene, PA4933, from published transcriptomic datasets of P. aeruginosa PA14 infecting RAW264.7 macrophages. Bioinformatic prediction preliminarily confirmed that PA4933 is a highly conserved seven-transmembrane protein sharing high structural homology with ABC transporters. Mechanistically, PA4933 elevates the transcription of glnA to enrich intracellular glutamine, thereby markedly boosting glutathione (GSH) biosynthesis and enhancing bacterial antioxidant capacity. Meanwhile, PA4933 represses the transcription of virulence-related genes including phzC, rhlA, pel, motA, and motC, which consequently inhibits pyocyanin production, rhamnolipid synthesis, biofilm formation and swarming motility. Such regulatory effects alleviate bacterial damage to multiple infection models, including A549 alveolar epithelial cells, Galleria mellonella larvae and murine acute pneumonia models. Collectively, PA4933 exerts dual regulatory roles: facilitating antioxidant immune evasion while suppressing virulence and mitigating host tissue injury. This protein regulates the infection homeostasis of PAO1, it provides new insights into P. aeruginosa infection.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108878"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207305","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}