Zhongshan Hospital, Fudan University, Shanghai, China.
Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Front Cell Infect Microbiol. 2021 Dec 3;11:792305. doi: 10.3389/fcimb.2021.792305. eCollection 2021.
is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming increasingly prevalent worldwide, the use of bacteriophages to treat pathogenic bacterial infections has recently gained attention. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapy. In this study, a total of 22 K isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and antibiotic susceptibility testing. In addition, the beta-lactamase gene () was characterized to determine the spread and outbreak of carbapenemase (KPC)-producing enterobacterial pathogens. Using these ST11 carbapenem-resistant isolates, three phages (NL_ZS_1, NL_ZS_2, and NL_ZS_3) from the family of were isolated and characterized to evaluate the application of lytic phages against the MDR isolates. inhibition assays with three phages and strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant and phage-sensitive mutants, suggesting several anti-phage mechanisms had developed in the host populations. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.
是社区获得性和医院获得性感染的主要原因，特别是在免疫功能低下的个体中。越来越多的多药耐药（MDR）分离株的出现显著影响了抗菌药物的效果。随着抗生素耐药性在全球范围内的日益普遍，利用噬菌体来治疗致病性细菌感染最近引起了关注。阐明噬菌体-细菌相互作用的细节将深入了解噬菌体生物学，并更好地发展噬菌体治疗。在这项研究中，通过多位点序列分型（MLST）、内切酶 S1 核酸酶脉冲场凝胶电泳（S1-PFGE）和抗生素敏感性测试，对总共 22 个 K 分离株进行了遗传和表型相关性评估。此外，还对β-内酰胺酶基因 () 进行了表征，以确定产碳青霉烯酶（KPC）肠杆菌病原体的传播和爆发。使用这些 ST11 碳青霉烯耐药 分离株，从 科中分离并表征了三种噬菌体（NL_ZS_1、NL_ZS_2 和 NL_ZS_3），以评估裂解噬菌体对 MDR 分离株的应用。三种噬菌体和 菌株 ZS15 的抑制试验表明噬菌体具有很强的裂解潜力，然而，随后噬菌体抗性和噬菌体敏感突变体的快速生长表明宿主群体中已经发展出几种抗噬菌体机制。总之，这些数据为已知的噬菌体生物学增加了更全面的知识，并进一步强调了它们的复杂性和未来挑战，以便在使用噬菌体控制这种重要的 MDR 细菌之前克服这些挑战。
