Bacteriophage induces modifications in outer membrane protein expression and antibiotic susceptibility in Acinetobacter baumannii

IF 7.7 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Srajana Nayak , Vijay Gundmi Apurva , Pallavi Bhat Ajakkala , Somanath Disha , Juliet Mohan Raj , Vijaya Kumar Deekshit , Biswajit Maiti
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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.
噬菌体诱导鲍曼不动杆菌外膜蛋白表达和抗生素敏感性的改变。
噬菌体是最丰富的针对细菌的生物制剂,为对抗鲍曼不动杆菌等多重耐药病原体提供了一种有希望的抗生素替代品。然而,噬菌体耐药性的快速发展带来了重大挑战。本研究强调了外膜蛋白(OMPs)在鲍曼不动杆菌噬菌体耐药性出现中的作用。研究了噬菌体敏感和耐药菌株的原生OMP谱。通过噬菌体感染细菌并继代培养产生耐噬菌体鲍曼不动杆菌,并对其OMP表达和毒力进行进一步表征。这些耐药菌株显著下调omp基因和低表达omp。表型变化,如减少对噬菌体的吸附,生长速率异常,生物膜形成能力,在限制条件下的更高存活率,更高的运动性和更高的碱性蛋白酶产量,在具有更好的生存和毒力的噬菌体耐受菌株中观察到。耐药菌株对它们以前抵抗的抗生素重新敏感。在噬菌体耐受菌株中显著低表达的OMPs被鉴定为OmpA和其他类似于OmpA的OMPs。本研究可以鉴定出某些在噬菌体暴露时显著低表达的OMPs。除了噬菌体耐药性的发展和对抗生素的再致敏外,耐药细菌还改变了表型特性,这为噬菌体治疗的未来铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International Journal of Biological Macromolecules
International Journal of Biological Macromolecules 生物-生化与分子生物学
CiteScore
13.70
自引率
9.80%
发文量
2728
审稿时长
64 days
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.
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