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靶向多重耐药菌的新型噬菌体的基因组和功能特征分析

Genomic and Functional Characterization of Novel Phages Targeting Multidrug-Resistant .

作者信息

Orozco-Ochoa Alma Karen, Quiñones Beatriz, González-Gómez Jean Pierre, Castro-Del Campo Nohelia, Valdez-Torres José Benigno, Chaidez-Quiroz Cristóbal

机构信息

Laboratorio Nacional para la Investigación en Inocuidad Alimentaria (LANIIA), Centro de Investigación en Alimentación y Desarrollo, A.C. (CIAD), Carretera a Eldorado Km 5.5, Campo El Diez, Culiacán 80110, Sinaloa, Mexico.

Produce Safety and Microbiology Research Unit, Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, CA 94710, USA.

出版信息

Int J Mol Sci. 2025 Jun 26;26(13):6141. doi: 10.3390/ijms26136141.

Abstract

is an opportunistic pathogen and a major cause of nosocomial infections worldwide. This study aimed to isolate and characterize phages with lytic activity against multidrug-resistant strains to enable antibacterial alternatives. Eight phages (AKO8a, PS118, B612, MCR, IDQ7, 89P13, CRL20, and CIM23) were isolated and subjected to genomic, phylogenetic, and functional analyses. Antibacterial activity was assessed in vitro against strain AbAK04 by measuring optical density over 17 h at multiplicities of infection (MOIs) of 0.1, 1, and 10, using a repeated-measures design with time as a crossed factor and MOI as a nested factor. Tukey's post-hoc test identified significant bacterial growth reductions of 57-72% ( < 0.001). Specifically, phages PS118 and 89P13 reduced growth by 71% at MOI 10; CIM23, B612, and CRL20 achieved 68% reduction at MOI 1; and MCR reduced growth by 64% at MOIs 0.1 and 1. Notably, lytic phage MCR encodes a glycosyl hydrolase family 58 (GH58) enzyme, potentially contributing to its antibacterial activity. Genomic analyses confirmed absence of virulence and antibiotic resistance genes, with all phages classified as novel species within the genus. These findings support the use of these phages as promising candidates for in vivo evaluation.

摘要

是一种机会致病菌,也是全球医院感染的主要原因。本研究旨在分离和鉴定对多重耐药菌株具有裂解活性的噬菌体,以提供抗菌替代方案。分离出8种噬菌体(AKO8a、PS118、B612、MCR、IDQ7、89P13、CRL20和CIM23),并对其进行基因组、系统发育和功能分析。通过在感染复数(MOI)为0.1、1和10的情况下,在17小时内测量光密度,采用以时间为交叉因素、MOI为嵌套因素的重复测量设计,对菌株AbAK04进行体外抗菌活性评估。Tukey事后检验确定细菌生长显著降低了57 - 72%(<0.001)。具体而言,噬菌体PS118和89P13在MOI为10时使生长降低了71%;CIM23、B612和CRL20在MOI为1时使生长降低了68%;MCR在MOI为0.1和1时使生长降低了64%。值得注意的是,裂解性噬菌体MCR编码一种糖基水解酶家族58(GH58)酶,可能有助于其抗菌活性。基因组分析证实没有毒力和抗生素抗性基因,所有噬菌体均被归类为该属内的新物种。这些发现支持将这些噬菌体作为体内评估的有前景候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613a/12249539/462ac72ac1a7/ijms-26-06141-g001.jpg

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