{"title":"Protection against DSS-induced colitis in mice through FcεRIα deficiency: the role of altered Lactobacillus","authors":"Yue Yin, Ruilong Wang, Yanning Li, Wenfei Qin, Letian Pan, Chenyuan Yan, Yusen Hu, Guangqiang Wang, Lianzhong Ai, Qixiang Mei, Li Li","doi":"10.1038/s41522-024-00563-z","DOIUrl":"https://doi.org/10.1038/s41522-024-00563-z","url":null,"abstract":"<p>The role of mast cells (MCs) in ulcerative colitis (UC) development is controversial. FcεRI, the IgE high-affinity receptor, is known to activate MCs. However, its role in UC remains unclear. In our study, Anti-FcεRI showed highly diagnostic value for UC. FcεRIα knockout in mice ameliorated DSS-induced colitis in a gut microbiota-dependent manner. Increased <i>Lactobacillus</i> abundance in FcεRIα deficient mice showed strongly correlation with the remission of colitis. RNA sequencing indicated activation of the NLRP6 inflammasome pathway in FcεRIα knockout mice. Additionally, <i>Lactobacillus plantarum</i> supplementation protected against inflammatory injury and goblet cell loss, with activation of the NLRP6 inflammasome during colitis. Notably, this effect was absent when the strain is unable to produce lactic acid. In summary, colitis was mitigated in FcεRIα deficient mice, which may be attributed to the increased abundance of <i>Lactobacillus</i>. These findings contribute to a better understanding of the relationship between allergic reactions, microbiota, and colitis.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214713","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":"Integrating respiratory microbiome and host immune response through machine learning for respiratory tract infection diagnosis","authors":"Hongbin Chen, Tianqi Qi, Siyu Guo, Xiaoyang Zhang, Minghua Zhan, Si Liu, Yuyao Yin, Yifan Guo, Yawei Zhang, Chunjiang Zhao, Xiaojuan Wang, Hui Wang","doi":"10.1038/s41522-024-00548-y","DOIUrl":"https://doi.org/10.1038/s41522-024-00548-y","url":null,"abstract":"<p>At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832–1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214521","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}
Tianyuan Jia, Xianbiao Bi, Menglu Li, Chenhui Zhang, Anmin Ren, Shangru Li, Tian Zhou, Yingdan Zhang, Yang Liu, Xue Liu, Yinyue Deng, Bin Liu, Guobao Li, Liang Yang
{"title":"Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence","authors":"Tianyuan Jia, Xianbiao Bi, Menglu Li, Chenhui Zhang, Anmin Ren, Shangru Li, Tian Zhou, Yingdan Zhang, Yang Liu, Xue Liu, Yinyue Deng, Bin Liu, Guobao Li, Liang Yang","doi":"10.1038/s41522-024-00550-4","DOIUrl":"https://doi.org/10.1038/s41522-024-00550-4","url":null,"abstract":"<p><i>Pseudomonas aeruginosa</i> is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in <i>P. aeruginosa</i> PAO1, PqsS, which promotes bacterial pathogenicity and <i>pseudomonas quinolone signal</i> quorum sensing (<i>pqs</i> QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed <i>pqsL</i> transcript, increasing PQS levels for <i>pqs</i> QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the <i>pqsL</i> mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on <i>P. aeruginosa</i> pathogenesis and targeted treatment.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226935","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}
Sunjae Lee, Victoria Meslier, Gholamreza Bidkhori, Fernando Garcia-Guevara, Lucie Etienne-Mesmin, Frederick Clasen, Junseok Park, Florian Plaza Oñate, Haizhuang Cai, Emmanuelle Le Chatelier, Nicolas Pons, Marcela Pereira, Maike Seifert, Fredrik Boulund, Lars Engstrand, Doheon Lee, Gordon Proctor, Adil Mardinoglu, Stéphanie Blanquet-Diot, David Moyes, Mathieu Almeida, S Dusko Ehrlich, Mathias Uhlen, Saeed Shoaie
{"title":"Transient colonizing microbes promote gut dysbiosis and functional impairment.","authors":"Sunjae Lee, Victoria Meslier, Gholamreza Bidkhori, Fernando Garcia-Guevara, Lucie Etienne-Mesmin, Frederick Clasen, Junseok Park, Florian Plaza Oñate, Haizhuang Cai, Emmanuelle Le Chatelier, Nicolas Pons, Marcela Pereira, Maike Seifert, Fredrik Boulund, Lars Engstrand, Doheon Lee, Gordon Proctor, Adil Mardinoglu, Stéphanie Blanquet-Diot, David Moyes, Mathieu Almeida, S Dusko Ehrlich, Mathias Uhlen, Saeed Shoaie","doi":"10.1038/s41522-024-00561-1","DOIUrl":"https://doi.org/10.1038/s41522-024-00561-1","url":null,"abstract":"<p><p>Species composition of the healthy adult gut microbiota tends to be stable over time. Destabilization of the gut microbiome under the influence of different factors is the main driver of the microbial dysbiosis and subsequent impacts on host physiology. Here, we used metagenomics data from a Swedish longitudinal cohort, to determine the stability of the gut microbiome and uncovered two distinct microbial species groups; persistent colonizing species (PCS) and transient colonizing species (TCS). We validated the continuation of this grouping, generating gut metagenomics data for additional time points from the same Swedish cohort. We evaluated the existence of PCS/TCS across different geographical regions and observed they are globally conserved features. To characterize PCS/TCS phenotypes, we performed bioreactor fermentation with faecal samples and metabolic modeling. Finally, using chronic disease gut metagenome and other multi-omics data, we identified roles of TCS in microbial dysbiosis and link with abnormal changes to host physiology.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154717","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}
Anthony M Bonacolta, Pieter T Visscher, Javier Del Campo, Richard Allen White Iii
{"title":"The eukaryome of modern microbialites reveals distinct colonization across aquatic ecosystems.","authors":"Anthony M Bonacolta, Pieter T Visscher, Javier Del Campo, Richard Allen White Iii","doi":"10.1038/s41522-024-00547-z","DOIUrl":"10.1038/s41522-024-00547-z","url":null,"abstract":"<p><p>Protists are less studied for their role and diversity in ecosystems. Notably, protists have played and still play an important role in microbialites. Microbialites, or lithified microbial mats, represent the oldest evidence of fossil biofilms (~3.5 Gyr). Modern microbialites may offer a unique proxy to study the potential role of protists within a geological context. We examined protist diversity in freshwater (Kelly and Pavilion Lake in British Columbia, Canada) and marine (Highborne Cay, Bahamas) to hypersaline (Shark Bay, Australia) microbialites to decipher their geomicrobiological role. The freshwater microbialite communities were clearly distinct from their marine and hypersaline counterparts. Chlorophytes had higher numerical abundance in freshwater microbialites; whereas pennate diatoms dominated numerically in marine microbialites. Despite the differences, protists across ecosystems may have adopted similar roles and functions. We suggest a consistent biogeochemical role of protists across microbialites globally; but that salinity may shape protist composition and evolution in these ecosystems.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel N Villageliu, Kelly C Cunningham, Deandra R Smith, Daren L Knoell, Mason Mandolfo, Todd A Wyatt, Derrick R Samuelson
{"title":"Natural killer cell effector function is critical for host defense against alcohol-associated bacterial pneumonia.","authors":"Daniel N Villageliu, Kelly C Cunningham, Deandra R Smith, Daren L Knoell, Mason Mandolfo, Todd A Wyatt, Derrick R Samuelson","doi":"10.1038/s41522-024-00558-w","DOIUrl":"10.1038/s41522-024-00558-w","url":null,"abstract":"<p><p>Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon receptor (AhR) signaling. Employing a binge-on-chronic alcohol-feeding model we sought to define the role and interaction of indole and NK cells during pulmonary host defense against alcohol-associated pneumonia. We demonstrate that alcohol dysregulates NK cell effector function and pulmonary recruitment via alterations in two key signaling pathways. We found that alcohol increases transforming growth factor beta (TGF-β) signaling while suppressing AhR signaling. We further demonstrated that NK cells isolated from alcohol-fed mice have a reduced ability to kill Klebsiella pneumoniae. NK cell migratory capacity to chemokines was also significantly altered by alcohol, as NK cells isolated from alcohol-fed mice exhibited preferential migration in response to CXCR3 chemokines but exhibited reduced migration in response to CCR2, CXCR4, and CX3CR1 chemokines. Together this data suggests that alcohol disrupts NK cell-specific TGF-β and AhR signaling pathways leading to decreased pulmonary recruitment and cytolytic activity thereby increasing susceptibility to alcohol-associated bacterial pneumonia.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E Gonzalez, M D Lee, B T Tierney, N Lipieta, P Flores, M Mishra, L Beckett, A Finkelstein, A Mo, P Walton, F Karouia, R Barker, R J Jansen, S J Green, S Weging, J Kelliher, N K Singh, D Bezdan, J Galazska, N J B Brereton
{"title":"Spaceflight alters host-gut microbiota interactions.","authors":"E Gonzalez, M D Lee, B T Tierney, N Lipieta, P Flores, M Mishra, L Beckett, A Finkelstein, A Mo, P Walton, F Karouia, R Barker, R J Jansen, S J Green, S Weging, J Kelliher, N K Singh, D Bezdan, J Galazska, N J B Brereton","doi":"10.1038/s41522-024-00545-1","DOIUrl":"https://doi.org/10.1038/s41522-024-00545-1","url":null,"abstract":"<p><p>The ISS rodent habitat has provided crucial insights into the impact of spaceflight on mammals, inducing symptoms characteristic of liver disease, insulin resistance, osteopenia, and myopathy. Although these physiological responses can involve the microbiome on Earth, host-microbiota interactions during spaceflight are still being elucidated. We explore murine gut microbiota and host gene expression in the colon and liver after 29 and 56 days of spaceflight using multiomics. Metagenomics revealed significant changes in 44 microbiome species, including relative reductions in bile acid and butyrate metabolising bacteria like Extibacter muris and Dysosmobacter welbionis. Functional prediction indicate over-representation of fatty acid and bile acid metabolism, extracellular matrix interactions, and antibiotic resistance genes. Host gene expression described corresponding changes to bile acid and energy metabolism, and immune suppression. These changes imply that interactions at the host-gut microbiome interface contribute to spaceflight pathology and that these interactions might critically influence human health and long-duration spaceflight feasibility.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Philipp Licht, Nazzareno Dominelli, Johannes Kleemann, Stefan Pastore, Elena-Sophia Müller, Maximilian Haist, Kim Sophie Hartmann, Henner Stege, Matthias Bros, Markus Meissner, Stephan Grabbe, Ralf Heermann, Volker Mailänder
{"title":"The skin microbiome stratifies patients with cutaneous T cell lymphoma and determines event-free survival.","authors":"Philipp Licht, Nazzareno Dominelli, Johannes Kleemann, Stefan Pastore, Elena-Sophia Müller, Maximilian Haist, Kim Sophie Hartmann, Henner Stege, Matthias Bros, Markus Meissner, Stephan Grabbe, Ralf Heermann, Volker Mailänder","doi":"10.1038/s41522-024-00542-4","DOIUrl":"https://doi.org/10.1038/s41522-024-00542-4","url":null,"abstract":"<p><p>Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam M Hamilton, Lisa Blackmer-Raynolds, Yaqing Li, Sean D Kelly, Nardos Kebede, Anna E Williams, Jianjun Chang, Sandra M Garraway, Shanthi Srinivasan, Timothy R Sampson
{"title":"Diet-microbiome interactions promote enteric nervous system resilience following spinal cord injury.","authors":"Adam M Hamilton, Lisa Blackmer-Raynolds, Yaqing Li, Sean D Kelly, Nardos Kebede, Anna E Williams, Jianjun Chang, Sandra M Garraway, Shanthi Srinivasan, Timothy R Sampson","doi":"10.1038/s41522-024-00556-y","DOIUrl":"10.1038/s41522-024-00556-y","url":null,"abstract":"<p><p>Spinal cord injury (SCI) results in numerous systemic dysfunctions, including intestinal dysmotility and enteric nervous system (ENS) atrophy. The ENS has capacity to recover following perturbation, yet intestinal pathologies persist. With emerging evidence demonstrating SCI-induced alterations to gut microbiome composition, we hypothesized that microbiome modulation contributes to post-injury enteric recovery. Here, we show that intervention with the dietary fiber, inulin, prevents SCI-induced ENS atrophy and dysmotility in mice. While SCI-associated microbiomes and specific injury-sensitive gut microbes are not sufficient to modulate intestinal dysmotility after injury, intervention with microbially-derived short-chain fatty acid (SCFA) metabolites prevents ENS dysfunctions in injured mice. Notably, inulin-mediated resilience is dependent on IL-10 signaling, highlighting a critical diet-microbiome-immune axis that promotes ENS resilience post-injury. Overall, we demonstrate that diet and microbially-derived signals distinctly impact ENS survival after traumatic spinal injury and represent a foundation to uncover etiological mechanisms and future therapeutics for SCI-induced neurogenic bowel.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baixing Chen, Luis Ponce Benavente, Marco Chittò, Virginia Post, Caroline Constant, Stephan Zeiter, Pamela Nylund, Matteo D'Este, Mercedes González Moreno, Andrej Trampuz, Jeroen Wagemans, Rob Lavigne, Jolien Onsea, R Geoff Richards, Willem-Jan Metsemakers, T Fintan Moriarty
{"title":"Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections.","authors":"Baixing Chen, Luis Ponce Benavente, Marco Chittò, Virginia Post, Caroline Constant, Stephan Zeiter, Pamela Nylund, Matteo D'Este, Mercedes González Moreno, Andrej Trampuz, Jeroen Wagemans, Rob Lavigne, Jolien Onsea, R Geoff Richards, Willem-Jan Metsemakers, T Fintan Moriarty","doi":"10.1038/s41522-024-00552-2","DOIUrl":"https://doi.org/10.1038/s41522-024-00552-2","url":null,"abstract":"<p><p>Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 10<sup>3</sup> PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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