Microbiological research最新文献

{"title":"Cobalamin-mediated protection of Faecalibacterium duncaniae against oxidative stress: Insights from proteomic and membrane fatty acid profiles","authors":"Maria Alejandra de Angel Fontalvo ,&nbsp;Simon Ménard ,&nbsp;Rime Chebbo ,&nbsp;Jasmina Vidic ,&nbsp;Alban Amoros ,&nbsp;Christine Péchoux ,&nbsp;Lydie Oliveira Correia ,&nbsp;Sébastien Dupont ,&nbsp;Florence Dubois-Brissonnet ,&nbsp;Laurent Beney ,&nbsp;Bonastre Oliete ,&nbsp;Jean-Marc Chatel ,&nbsp;Sandrine Auger","doi":"10.1016/j.micres.2026.128455","DOIUrl":"10.1016/j.micres.2026.128455","url":null,"abstract":"<div><div><em>Faecalibacterium</em> species are keystone commensals of the human gut, contributing to intestinal homeostasis, immune modulation, and epithelial health. However, their extreme sensitivity to oxygen and reactive oxygen species renders them highly vulnerable during inflammatory conditions, severely limiting their therapeutic application. Understanding the molecular mechanisms underlying their oxidative stress responses is therefore critical for harnessing these bacteria as next-generation probiotics to restore gut health. In this study, we investigated oxidative stress responses in <em>Faecalibacterium duncaniae</em> A2–165 using comprehensive proteomic and membrane fatty acid profiling. We demonstrated that increasing hydrogen peroxide (H₂O₂) concentrations extend the lag phase of growth and affect survival during the first hour of exposure, notably altering the redox potential. Exposure to H₂O₂ triggered a remodeling of the proteome, including detoxification systems, metal transporters, DNA repair systems, transcriptional regulators, and enzymes involved in cobalamin biosynthesis. Complementary RT-qPCR analyses revealed coordinated and time-dependent transcriptional activation of genes involved in oxidative stress response. Remarkably, cobalamin supplementation enhanced bacterial growth, mitigated H₂O₂-induced stress, and lowered superoxide levels in <em>F. duncaniae,</em> highlighting its direct antioxidant activity. By analyzing membrane fatty acid profiles, we showed that cobalamin preserves membrane fluidity, counteracting oxidative stress induced by H₂O₂ in <em>F. duncaniae.</em> These findings reveal the multifaceted strategies employed by <em>F. duncaniae</em> to withstand oxidative stress and provide a foundation for future efforts to optimize its production at industrial scales and its therapeutic potential as a next-generation probiotic.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"306 ","pages":"Article 128455"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of phage tail fiber proteins to counter bacterial resistance and improve biocontrol efficacy in plant disease models","authors":"Xinyan Xu ,&nbsp;Xuefang Huang ,&nbsp;Luokai Wang ,&nbsp;Jingxian Yang ,&nbsp;Munazza Ijaz ,&nbsp;Jianping Chen ,&nbsp;Kotaro Kiga ,&nbsp;Bin Li","doi":"10.1016/j.micres.2026.128459","DOIUrl":"10.1016/j.micres.2026.128459","url":null,"abstract":"<div><div>Phage therapy is being used to combat pathogenic bacterial infections that threaten plant, animal, and human health. However, its application remains limited by high host specificity and the emergence of bacterial resistance. In this study, we addressed the key issues in phage therapy using rice bacterial blight pathogen <em>Xanthomonas oryzae</em> pv<em>. oryzae</em> (<em>Xoo</em>) strain N1 and its lytic phage NP1. Strain N1 acquired resistance to the phage NP1 through mutations and downregulation of lipopolysaccharide (LPS) biosynthesis genes. A directed evolution assay using phage NP1 and the resistant strain N1R resulted in the development of phage E12–2, which overcame bacterial resistance, expanded its host range and improved bacterial suppression by targeting alternative LPS binding sites. Moreover, genome analysis identified two amino acid substitutions (V303L and G317V) in its tail fiber protein. Additionally, phage E12–2 improved disease control efficiency by 51 % compared to the wild-type phage NP1 and induced plant immunity in a plant disease model. These findings enhance our understanding of how bacteria-phage evolution shapes the dynamics of phage therapy in plants.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"306 ","pages":"Article 128459"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of a Con7-related transcription factor in Coprinopsis cinerea indicates evolutionary conservation of morphogenetic roles","authors":"Hongli Wu ,&nbsp;Zsolt Merényi ,&nbsp;Máté Virágh ,&nbsp;Xiao-Bin Liu ,&nbsp;Botond Hegedüs ,&nbsp;Zhihao Hou ,&nbsp;Edit Ábrahám ,&nbsp;Anett Fürtön ,&nbsp;Zsolt Kristóffy ,&nbsp;Zoltán Lipinszki ,&nbsp;László G. Nagy","doi":"10.1016/j.micres.2026.128462","DOIUrl":"10.1016/j.micres.2026.128462","url":null,"abstract":"<div><div>Fruiting bodies of mushroom-forming fungi (Agaricomycetes) exhibit the highest degree of multicellular complexity in fungi, yet the molecular underpinnings of their developmental programs remain incompletely understood. Here, we characterize <em>gcd1</em>, a gene encoding a transcription factor in the Con7 subfamily of C2H2-type zinc finger proteins. This subfamily has previously been implicated in pathogenic morphogenesis in Ascomycota, but its role in Agaricomycetes has not previously been addressed. In <em>Coprinopsis cinerea</em>, CRISPR/Cas9-mediated deletion of <em>gcd1</em> resulted in strains with severely impaired fruiting body morphogenesis, with malformed cap, stipe, and gill tissues. <em>Gcd1</em> deletion strains lacked universal veil, resembling species with open (gymnocarpous) development. We find that GCD1/Con7 homologs are widely distributed in most Dikarya species and are mostly encoded by a single gene in each species’ genome. Transcriptome analyses identified several misregulated genes in the Δ<em>gcd1</em> mutant, which pinpoint potential mechanisms underlying its developmental defects as well as provided insights into the morphogenesis of mushroom fruiting bodies. These findings establish GCD1 as a key regulator of multicellular development in <em>C. cinerea</em> and broaden the known functions of Con7-like transcription factors to include fruiting body morphogenesis in Agaricomycetes. Overall, our results and the morphogenetic role of Con7-like transcription factors of Ascomycota suggest functional conservation over half a billion years of evolution.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"306 ","pages":"Article 128462"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial diversity loss affects old and modern barley cultivars differently under varying nitrogen sources","authors":"Nikolaj L. Kindtler ,&nbsp;Sanea Sheikh ,&nbsp;Rujia He ,&nbsp;Rute R.da Fonseca ,&nbsp;Kristian H. Laursen ,&nbsp;Flemming Ekelund","doi":"10.1016/j.micres.2026.128458","DOIUrl":"10.1016/j.micres.2026.128458","url":null,"abstract":"<div><div>Soil microbial diversity is crucial for plant nutrition and health, yet how its loss affects plant performance remains unclear. We used a dilution-to-extinction approach to test how declining rhizo-microbiome diversity influences two barley cultivars: the modern RGT Planet and the older Babushka. Plants were grown in sterilized systems amended with mineral or organic nitrogen and inoculated with microbiome treatments (10^-¹, 10^-³, 10^-⁵, and 10^-⁷ dilutions), plus a no-inoculum treatment. We used amplicon sequencing (16S, ITS, 18S) to profile rhizosphere communities, and quantified plant biomass, shoot nitrogen, and chitin mineralization. Protists and fungi were present in 10^-¹ and 10^-³ but absent in all others. Microbiome inoculum and nitrogen source explained most variation in rhizo-microbiome composition, with cultivar having a smaller effect. Under organic nitrogen, Babushka showed a marked decline in biomass with decreasing diversity, whereas RGT was largely unaffected, indicating that the older cultivar relied more on a diverse microbiome to maintain growth. At intermediate diversity, when protists and fungi were lost, both cultivars showed improved growth and shoot nitrogen, coinciding with shifts in bacterial composition and loss of potential pathogens. Hence, reduced diversity did not always impair growth, suggesting functional compensation. Under mineral nitrogen, both cultivars were less sensitive to diversity loss. Overall, nitrogen source and cultivar identity modulated plant responses to microbial diversity loss. Diverse microbiomes promoted efficient use of organic nitrogen, particularly for the older cultivar, while the modern cultivar maintained growth at lower diversity. Our results demonstrate that the consequences of diversity loss are context-dependent and cultivar-specific.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"306 ","pages":"Article 128458"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective role of the gut microbiota against Listeria monocytogenes: From colonization resistance to therapeutic approaches","authors":"Junnan Huang ,&nbsp;Xuejuan Xia ,&nbsp;Jing Lu ,&nbsp;Xuanyu Chen ,&nbsp;Keyao Ye ,&nbsp;Jia Yu ,&nbsp;Zhuosi Li ,&nbsp;Yue Ma ,&nbsp;Xiaojie Qin ,&nbsp;Yangtai Liu ,&nbsp;Xiang Wang ,&nbsp;Hai Chi ,&nbsp;Guannan Li ,&nbsp;Chang Liu ,&nbsp;Qingli Dong","doi":"10.1016/j.micres.2026.128454","DOIUrl":"10.1016/j.micres.2026.128454","url":null,"abstract":"<div><div><em>Listeria monocytogenes</em> (LM) is a significant foodborne pathogen with considerable resilience in diverse environments. Following ingestion via contaminated food, LM can breach the intestinal barrier and infect target organs, causing systemic infection. This breach represents a critical step in its pathogenesis. The gut microbiota, a key component of intestinal defense, can restrict the colonization and invasion of the pathogen through mechanisms such as nutrient competition and bacteriocin production. In response, LM has evolved counterstrategies to enhance its survival and invasiveness in the gut environment. Furthermore, the efficacy of the gut microbiota in resisting LM is influenced by multiple factors, such as population differences and dietary habits, leading to variations in susceptibility to infection among individuals. Currently, antibiotic therapy for listeriosis faces limitations, highlighting the need for alternative control and therapeutic strategies. This review systematically summarizes the mechanisms by which the gut microbiota resists LM, the adaptive strategies of the pathogen, and the factors influencing this interaction. It also discusses current microbiota-based preventive and therapeutic approaches, aiming to provide a theoretical foundation for future research.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"306 ","pages":"Article 128454"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated high-throughput microscopy screening unveiled new Listeria monocytogenes genes involved in cell infection","authors":"Ângela Alves ,&nbsp;Diana Meireles ,&nbsp;Chiara Suriano ,&nbsp;Ricardo Monteiro ,&nbsp;Rute Oliveira ,&nbsp;Beatriz G. Bernardes ,&nbsp;Sandra Sousa ,&nbsp;Rita Pombinho ,&nbsp;Didier Cabanes","doi":"10.1016/j.micres.2026.128442","DOIUrl":"10.1016/j.micres.2026.128442","url":null,"abstract":"<div><div>To uncover novel genetic factors required for <em>Listeria monocytogenes</em> cell infection, we developed an automated high-throughput microscopy screening pipeline that integrates GFP-expressing <em>bacteria</em> with machine learning-based image analysis. Using this approach, we screened a mariner transposon library comprising 4224 <em>L. monocytogenes</em> EGDe mutants and identified 58 with significantly reduced numbers of intracellular bacteria. Sequencing revealed 24 unique insertion sites corresponding to 14 genes, including previously known virulence factors and nine novel candidates not previously implicated in cell infection. These genes encode the protease chaperone ClpX, the ferric uptake regulator Fur, the sensor histidine kinase LisK, the peptide chain release factor 2 PrfB, proteins involved in proline and purine biosynthesis (ProAB, PurAB), and Lmo2217, a protein of unknown function. Among these, the targeted deletion of the adenylosuccinate synthetase gene, <em>purA</em>, resulted in impaired growth in minimal medium, severely reduced proliferation in epithelial and macrophage cell lines, and attenuated virulence in mice. Unexpectedly, PurA was also essential for bacterial internalization into cells. Supplementation with AMP or adenine, but not ATP, rescued the invasion capacity of the Δ<em>purA</em> mutant. Mechanistically, <em>purA</em> deletion induced a reduction in the levels of surface-associated GAPDH, a putative plasminogen-binding protein, likely contributing to the observed invasion defect. Overall, these findings highlight the power of automated high-throughput microscopy screening to dissect host–pathogen interactions, identify novel <em>L. monocytogenes</em> genes required for cell infection, and uncover an unexpected role for PurA in maintaining GAPDH surface localization and promoting bacterial entry into host cells.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"306 ","pages":"Article 128442"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural product honokiol exerts anti-methicillin resistant Staphylococcus aureus infection activity by targeting pyruvate kinase to inhibit glucose metabolism","authors":"Jingwen Bai,&nbsp;Jinjin Zheng,&nbsp;Chi Wei,&nbsp;Bin Yu,&nbsp;Jingwen Sun,&nbsp;Ziyang Feng,&nbsp;Yu Yang","doi":"10.1016/j.micres.2026.128451","DOIUrl":"10.1016/j.micres.2026.128451","url":null,"abstract":"<div><div>The global spread of methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) urgently demands novel therapeutic strategies. This study demonstrates that honokiol (HNK), a natural biphenolic compound, is a potent and broad-spectrum agent against MRSA, including clinical isolates. HNK exhibited rapid bactericidal activity, effectively disrupted biofilms, and in a murine abscess model, significantly promoted wound healing while reducing pro-inflammatory cytokines, with excellent biocompatibility. Through an integrated multi-omics, biochemical, and biophysical approach, we identified pyruvate kinase (PYK), the terminal enzyme of glycolysis, as the primary cellular target. Remarkably, HNK employs a dual-targeting strategy, concurrently inhibiting PYK enzyme activity and downregulating <em>pyk</em> gene transcription. Molecular docking, dynamics simulations, and computational mutagenesis delineated the precise binding mode and validated key interaction residues. This concerted attack triggers a catastrophic metabolic cascade severe obstruction of glycolytic flux, impairment of the TCA cycle, profound depletion of ATP/NADH, and oxidative stress ultimately leading to bacterial death and virulence attenuation. Our findings not only elucidate a novel antibacterial mechanism centered on the simultaneous transcriptional and functional inhibition of a metabolic hub but also provide a structural basis for drug design, positioning HNK as a valuable lead compound against multidrug-resistant staphylococcal infections. The definitive genetic validation of PYK as the essential target remains the critical next step to advance this therapeutic strategy.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"306 ","pages":"Article 128451"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HsbA represses stationary phase biofilm formation in Pseudomonas putida","authors":"Marta Pulido-Sánchez ,&nbsp;Elisa Montero-Beltrán ,&nbsp;Aroa López-Sánchez ,&nbsp;Fernando Govantes","doi":"10.1016/j.micres.2025.128428","DOIUrl":"10.1016/j.micres.2025.128428","url":null,"abstract":"<div><div><em>Pseudomonas putida</em> biofilm growth is associated to nutrient-sufficient conditions and biofilm dispersal is induced by nutrient starvation, signaled by the stringent response-associated nucleotide alarmone (p)ppGpp. We have used transcriptomic analysis to show that (p)ppGpp regulates the <em>hsbAR-hptB</em> gene cluster, encoding components of a phosphorelay pathway and an anti-σ factor antagonist, and <em>cfcR</em>, encoding a response regulator with diguanylate cyclase (DGC) activity. Transcription of <em>hsbAR-hptB</em> and <em>cfcR</em> is RpoS-dependent and induced by stationary phase and the stringent response. A ∆<em>hsbA</em> mutant resumed biofilm formation after dispersal in late stationary phase and displayed increased pellicle formation at the medium-air interphase and Congo Red adsorption. All these phenotypes were traced down to increased c-di-GMP levels in stationary phase, dependent on the activity of CfcR and its cognate sensor kinase, CfcA. HsbA was reversibly phosphorylated by the combined action of HptB and HsbR. HsbA phosphorylation conditioned its interaction with CfcR and CfcA and the subcellular distribution of the three proteins. In spite of this, HsbA retained its ability to prevent biofilm formation regardless of its phosphorylation state. Our results support a model in which HsbA forms a complex with CfcR to inhibit its DGC activity regardless of its phosphorylation state. Upon HsbA dephosphorylation, this complex is recruited to the cell membrane by CfcA to strengthen the inhibitory effect. While this pathway contributes to biofilm dispersal by denying <em>de novo</em> c-di-GMP synthesis during nutrient starvation, it may also enable quick restoration of the biofilm phenotype to colonize new sites or during biofilm maturation.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"305 ","pages":"Article 128428"},"PeriodicalIF":6.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic regulation of K33- and K48-linked ubiquitination of Tip60 by TRIM37 orchestrates host DNA damage response during Pseudomonas aeruginosa infection and recovery","authors":"Hua Yu ,&nbsp;Xingmin Wang ,&nbsp;Junzhi Xiong,&nbsp;Xiaomei He,&nbsp;Caifeng Ma,&nbsp;Qilin Wang,&nbsp;Rongrong Chen,&nbsp;Yuanyuan Li,&nbsp;Qian Dai,&nbsp;Qian Min,&nbsp;Jianyun Zhou,&nbsp;Kebin Zhang","doi":"10.1016/j.micres.2025.128414","DOIUrl":"10.1016/j.micres.2025.128414","url":null,"abstract":"<div><div>Bacterial infections pose a significant threat to host cells by inducing DNA damage, potentially leading to chromosomal instability, cell cycle arrest, apoptosis, or even cancer. <em>Pseudomonas aeruginosa</em> (<em>P. aeruginosa</em>) infection-induced DNA double-strand breaks (DSBs) activates DNA damage response (DDR) to facilitate repair. However, the mechanisms linking <em>P. aeruginosa</em> infection and host DNA repair remain unclear. Here, we demonstrate that DSBs-induced by <em>P. aeruginosa</em> in lung epithelial cells promote Tip60 activation and stabilization, which help counteract DNA damage. However, diminished Tip60 activation and reduced protein levels during the post-infection recovery phase exacerbate DNA damage. Mechanistically, elevated Tip60 levels during infection are associated with suppressed K33- and K48-linked ubiquitination, whereas the decline of Tip60 during recovery coincides with enhanced K33- and K48-linked ubiquitination. These specific ubiquitination modifications promote proteasomal degradation of Tip60, thereby reducing its stability. Supporting this, we observed that wild-type Tip60 undergoes markedly less K33- and K48-linked ubiquitination than its histone acetyltransferase (HAT) activity-deficient mutant. Notably, we identify the E3 ubiquitin ligase TRIM37 as a positive regulator of Tip60 stability, largely independent of its E3 ligase activity. Silencing TRIM37 enhances K33- and K48-linked ubiquitination and accelerates Tip60 degradation, thereby exacerbating DNA damage during both infection and recovery. TRIM37 binds to the C-terminal MYST domain of Tip60, with this interaction strengthened during infection but weakened upon recovery. This dynamic regulation arises because TRIM37 preferentially associates with the activated form of Tip60. Collectively, our findings identify the TRIM37-Tip60 axis as a critical regulator of host DDR in response to <em>P. aeruginosa</em> infection, offering new insights into infection-associated DDR and therapeutic strategies.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"305 ","pages":"Article 128414"},"PeriodicalIF":6.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of phage therapy for drug-resistant Pseudomonas aeruginosa infections","authors":"Xiao Yu ,&nbsp;Jinbei Zhang ,&nbsp;Xiangmei Li ,&nbsp;Guyu Li ,&nbsp;Xiaoxiao Lu ,&nbsp;Yinghan Shi ,&nbsp;Wei Lin ,&nbsp;Xiuli Wang ,&nbsp;Weihua Zhang ,&nbsp;Yigang Tong ,&nbsp;Mengzhe Li ,&nbsp;Lixin Xie ,&nbsp;Mengying Yao","doi":"10.1016/j.micres.2025.128417","DOIUrl":"10.1016/j.micres.2025.128417","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> is a major opportunistic pathogen implicated in a wide range of infections, including chronic respiratory infections, burn wound infections, urinary tract infections, and device-associated infections. Its intrinsic and acquired resistance mechanisms, particularly its capacity for biofilm formation, pose serious challenges to conventional antibiotic therapy. With the continued rise of multidrug-resistant and pan-drug-resistant strains, the need for alternative therapeutic strategies has become increasingly urgent. Phages, viruses that specifically recognize and lyse bacteria, have shown unique advantages in combating antibiotic-resistant infections. This review systematically summarizes recent advances in the application of phage therapy for <em>P. aeruginosa</em> infections, covering <em>in vitro</em> bactericidal activity, biofilm degradation, and synergistic interactions with antibiotics. We further discuss evidence from animal models, including therapeutic efficacy, immunomodulatory effects, and pharmacokinetics. Emphasis is placed on clinical use cases, including different routes of administration, symptom relief, biomarker modulation, pathogen clearance rates, and adverse events. Typical case reports and early-phase clinical trials support the safety and efficacy of phage therapy. Nevertheless, translational barriers persist, such as the need for precise host matching, risks of immune neutralization, and the lack of standardized regulatory frameworks and Good Manufacturing Practice (GMP)-grade production systems. The rapid development of engineered phages and individualized therapeutic approaches offers a feasible path forward. In conclusion, phage therapy holds significant promise for the treatment of drug-resistant <em>P. aeruginosa</em> infections, and future efforts should focus on establishing standardized systems, conducting multicenter clinical studies, and leveraging synthetic biology to accelerate its translation from bench to bedside.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"305 ","pages":"Article 128417"},"PeriodicalIF":6.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}