{"title":"Bacteriophage induces modifications in outer membrane protein expression and antibiotic susceptibility in Acinetobacter baumannii.","authors":"Srajana Nayak, Vijay Gundmi Apurva, Pallavi Bhat Ajakkala, Somanath Disha, Juliet Mohan Raj, Vijaya Kumar Deekshit, Biswajit Maiti","doi":"10.1016/j.ijbiomac.2025.139589","DOIUrl":null,"url":null,"abstract":"<p><p>Bacteriophages, the most abundant biological agents targeting bacteria, offer a promising alternative to antibiotics for combating multi-drug resistant pathogens like Acinetobacter baumannii. However, the rapid development of bacteriophage resistance poses a significant challenge. This study highlights the contribution of outer membrane proteins (OMPs) in the emergence of bacteriophage resistance in A. baumannii. The bacteriophage-sensitive and resistant isolates were studied for their native OMP profiles. Bacteriophage-tolerant A. baumannii were generated by infecting bacteria with bacteriophages and sub-culturing the survivors, and their expression of OMP and virulence was further characterized. These tolerant strains had significantly downregulated omp genes and under-expressed OMPs. Phenotypic changes like reduced adsorption to phages, deviant growth rates, biofilm-forming capacities, higher survival in limiting conditions, higher motility, and higher alkaline protease production were observed in the phage-tolerant strains equipped with better survival and virulent properties. The tolerant strains were re-sensitized to antibiotics they previously resisted. The significantly under-expressed OMPs in phage-tolerant strains were identified as OmpA and other OMPs similar to OmpA. This study could identify certain OMPs significantly under-expressed on bacteriophage exposure. The tolerant bacteria had altered phenotypic properties in addition to the development of phage resistance and the re-sensitisation to antibiotics, which paved the way for the future of phage therapeutics.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"139589"},"PeriodicalIF":7.7000,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Macromolecules","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.ijbiomac.2025.139589","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Bacteriophages, the most abundant biological agents targeting bacteria, offer a promising alternative to antibiotics for combating multi-drug resistant pathogens like Acinetobacter baumannii. However, the rapid development of bacteriophage resistance poses a significant challenge. This study highlights the contribution of outer membrane proteins (OMPs) in the emergence of bacteriophage resistance in A. baumannii. The bacteriophage-sensitive and resistant isolates were studied for their native OMP profiles. Bacteriophage-tolerant A. baumannii were generated by infecting bacteria with bacteriophages and sub-culturing the survivors, and their expression of OMP and virulence was further characterized. These tolerant strains had significantly downregulated omp genes and under-expressed OMPs. Phenotypic changes like reduced adsorption to phages, deviant growth rates, biofilm-forming capacities, higher survival in limiting conditions, higher motility, and higher alkaline protease production were observed in the phage-tolerant strains equipped with better survival and virulent properties. The tolerant strains were re-sensitized to antibiotics they previously resisted. The significantly under-expressed OMPs in phage-tolerant strains were identified as OmpA and other OMPs similar to OmpA. This study could identify certain OMPs significantly under-expressed on bacteriophage exposure. The tolerant bacteria had altered phenotypic properties in addition to the development of phage resistance and the re-sensitisation to antibiotics, which paved the way for the future of phage therapeutics.
期刊介绍:
The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.