Garretto Andrea, Dawid Suzanne, Woods Robert
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, United States of America.
medRxiv. 2024 Jul 18:2024.07.17.24310592. doi: 10.1101/2024.07.17.24310592.
Vancomycin resistant enterococci (VRE) are important pathogens in hospitalized patients, however, the factors involved in VRE colonization of hospitalized patients are not well characterized. Bacteriocins provide a competitive advantage to enterococci in experimental models of colonization, but little is known about bacteriocin content in samples derived from humans and even less is known about their dynamics in the clinical setting. To identify bacteriocins which may be relevant in the transmission of VRE, we present a systematic analysis of bacteriocin content in the genomes of 2,428 patient derived isolates collected over a six-year period from a single hospital system. We used computational methods to broadly search for bacteriocin structural genes and a functional assay to look for phenotypes consistent with bacteriocin expression. We identified homology to 15 different bacteriocins with two having high presence in this clinical cohort. Bacteriocin 43 (bac43) was found in a total of 58% of isolates, increasing from 8% to 91% presence over the six-year collection period. There was little genetic variation in the bac43 structural or immunity genes across isolates. The enterocin A structural gene was found in 98% of isolates but only 0.3% of isolates had an intact enterocin A gene cluster and displayed a bacteriocin producing phenotype. This study presents a wide survey of bacteriocins from hospital isolates and identified bac43 as highly conserved, increasing in prevalence, and phenotypically functional. This makes bac43 an interesting target for future investigation for a potential role in transmission.
While enterococci are a normal inhabitant of the human gut, vancomycin-resistant and are urgent public health threats responsible for hospital associated infections. Bacteriocins are ribosomally synthesized antimicrobial proteins and are commonly used by bacteria to provide a competitive advantage in polymicrobial environments. Bacteriocins have the potential be used by to invade and dominate the human gut leading to a greater propensity for transmission. In this work, we explore bacteriocin content in a defined clinically derived population of using both genetic and phenotypic studies. We show that one highly active bacteriocin is increasing in prevalence over time and demonstrates great potential relevance to transmission.
耐万古霉素肠球菌(VRE)是住院患者中的重要病原体,然而,住院患者VRE定植所涉及的因素尚未得到充分表征。在定植实验模型中,细菌素为肠球菌提供了竞争优势,但对于源自人类样本中的细菌素含量知之甚少,而关于它们在临床环境中的动态变化了解更少。为了鉴定可能与VRE传播相关的细菌素,我们对在六年期间从单一医院系统收集的2428株患者分离株的基因组中的细菌素含量进行了系统分析。我们使用计算方法广泛搜索细菌素结构基因,并通过功能测定来寻找与细菌素表达一致的表型。我们鉴定出与15种不同细菌素具有同源性,其中两种在该临床队列中高度存在。在总共58%的分离株中发现了细菌素43(bac43),在六年的收集期内从8%增加到91%。分离株中bac43结构或免疫基因的遗传变异很少。在98%的分离株中发现了肠球菌素A结构基因,但只有0.3%的分离株具有完整的肠球菌素A基因簇并表现出产生细菌素的表型。这项研究对医院分离株中的细菌素进行了广泛调查,并确定bac43高度保守、患病率增加且具有表型功能。这使得bac43成为未来研究其在传播中潜在作用的一个有趣靶点。
虽然肠球菌是人类肠道的正常居民,但耐万古霉素肠球菌是导致医院感染的紧迫公共卫生威胁。细菌素是核糖体合成的抗菌蛋白,细菌通常利用它们在多微生物环境中提供竞争优势。细菌素有可能被用于侵入并主导人类肠道,从而导致更大的传播倾向。在这项工作中,我们通过遗传和表型研究探索了特定临床来源人群中的细菌素含量。我们表明,一种高活性细菌素的患病率随时间增加,并且显示出与传播有很大的潜在相关性。