Department of Medical Biomaterials Engineering and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
Department of Medical Biomaterials Engineering and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
Microb Pathog. 2020 Jun;143:104159. doi: 10.1016/j.micpath.2020.104159. Epub 2020 Mar 18.
Bacteriophages have received great attention as an alternative over antibiotics due to the host specificity. Therefore, this study was designed to evaluate the associations between bacteriophage-insensitive (BI) and antibiotic-resistant mutants of Salmonella Typhimurium strains. Bacteriophage-sensitive (BS) Salmonella enterica serovar Typhimurium ATCC 19585 (BSST), ciprofloxacin-induced S. Typhimurium ATCC 19585 (BSST), S. Typhimurium KCCM 40253 (BSST), and clinically isolated multidrug-resistant S. Typhimurium CCARM 8009 (BSST) were used to induce the bacteriophage-insensitive mutants (BIST, BIST, BIST, and BIST), which were characterized by measuring mutant frequency lysogenic induction, phage adsorption, antibiotic susceptibility, and differential gene expression. The numbers of BSST, BSST, and BSST were reduced by P22 (>3 log), while the least lytic activity was observed for BSST, suggesting alteration in bacteriophage-binding receptors on the surface of multidrug-resistant strain. BSST treated with P22 showed the large variation in the cell state (CV>40%) and highest mutant frequency (62%), followed by 25% for BSST. The least similarities between BSST and BIST were observed for P22 and PBST-13 (<12%). The relative expression levels of bacteriophage-binding receptor-related genes (btuB, fhuA, fliK, fljB, ompC, ompF, rfaL, and tolC) were decreased in BIST and BIST. These results indicate that the bacteriophage resistance is highly associated with the antibiotic resistance. The findings in this study could pave the way for the application of bacteriophages as an alternative to control antibiotic-resistant bacteria.
噬菌体由于具有宿主特异性而受到极大关注，可以替代抗生素。因此，本研究旨在评估沙门氏菌噬菌体不敏感（BI）和抗生素耐药突变体之间的关联。使用噬菌体敏感（BS）鼠伤寒沙门氏菌血清型 Typhimurium ATCC 19585（BSST）、环丙沙星诱导的鼠伤寒沙门氏菌 ATCC 19585（BSST）、鼠伤寒沙门氏菌 KCCM 40253（BSST）和临床分离的多药耐药鼠伤寒沙门氏菌 CCARM 8009（BSST）诱导噬菌体不敏感突变体（BIST、BIST、BIST 和 BIST），通过测量突变频率溶原诱导、噬菌体吸附、抗生素敏感性和差异基因表达来表征这些突变体。P22 减少了 BSST、BSST 和 BSST 的数量（>3 log），而对多药耐药株的裂解活性最低，表明噬菌体结合受体在表面发生改变。用 P22 处理的 BSST 表现出细胞状态的巨大变化（CV>40%）和最高的突变频率（62%），其次是 BSST 的 25%。BSST 和 BIST 之间与 P22 和 PBST-13（<12%）的相似性最低。噬菌体结合受体相关基因（btuB、fhuA、fliK、fljB、ompC、ompF、rfaL 和 tolC）的相对表达水平在 BIST 和 BIST 中降低。这些结果表明噬菌体的耐药性与抗生素的耐药性密切相关。本研究的结果为噬菌体作为控制抗生素耐药细菌的替代物的应用铺平了道路。
