Genome-wide mutagenesis identifies factors involved in MRSA vaginal colonization.

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-03-13 DOI:10.1016/j.celrep.2025.115421

Laurie M Lyon, Stephanie M Marroquin, John C Thorstenson, Luke R Joyce, Ernesto J Fuentes, Kelly S Doran, Alexander R Horswill

{"title":"Genome-wide mutagenesis identifies factors involved in MRSA vaginal colonization.","authors":"Laurie M Lyon, Stephanie M Marroquin, John C Thorstenson, Luke R Joyce, Ernesto J Fuentes, Kelly S Doran, Alexander R Horswill","doi":"10.1016/j.celrep.2025.115421","DOIUrl":null,"url":null,"abstract":"<p><p>Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that colonizes various body sites, including the nares, skin, and vagina. During pregnancy,colonization can lead to dysbiosis, adverse pregnancy outcomes, and invasive disease. To identify genes contributing to MRSA vaginal fitness, we performed transposon sequencing (Tn-seq) using a murine model of vaginal colonization, identifying over 250 conditionally essential genes. Five genes were validated in our murine model, including those encoding the aerobic respiration protein QoxB, bacillithiol biosynthesis component BshB2, sialic acid catabolism enzyme NanE, and staphylococcal regulator of respiration SrrAB. RNA sequencing and comparative analysis identified over 30 SrrAB-regulated genes potentially important for fitness in vaginal-like conditions, particularly under oxygen stress. These findings highlight pathways such as aerobic respiration, bacillithiol biosynthesis, sialic acid catabolism, and transcriptional regulation that support MRSA's competitive fitness in the vaginal tract.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115421"},"PeriodicalIF":7.5000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2025.115421","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that colonizes various body sites, including the nares, skin, and vagina. During pregnancy,colonization can lead to dysbiosis, adverse pregnancy outcomes, and invasive disease. To identify genes contributing to MRSA vaginal fitness, we performed transposon sequencing (Tn-seq) using a murine model of vaginal colonization, identifying over 250 conditionally essential genes. Five genes were validated in our murine model, including those encoding the aerobic respiration protein QoxB, bacillithiol biosynthesis component BshB2, sialic acid catabolism enzyme NanE, and staphylococcal regulator of respiration SrrAB. RNA sequencing and comparative analysis identified over 30 SrrAB-regulated genes potentially important for fitness in vaginal-like conditions, particularly under oxygen stress. These findings highlight pathways such as aerobic respiration, bacillithiol biosynthesis, sialic acid catabolism, and transcriptional regulation that support MRSA's competitive fitness in the vaginal tract.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

耐甲氧西林金黄色葡萄球菌（MRSA）是一种机会性病原体，可在人体的不同部位定植，包括鼻腔、皮肤和阴道。在怀孕期间，定植可导致菌群失调、不良妊娠结局和侵袭性疾病。为了确定有助于MRSA阴道适应性的基因，我们利用小鼠阴道定植模型进行了转座子测序（Tn-seq），确定了250多个条件性必需基因。在我们的小鼠模型中验证了五个基因，包括编码有氧呼吸蛋白 QoxB、杆菌硫醇生物合成成分 BshB2、硅铝酸分解酶 NanE 和葡萄球菌呼吸调节因子 SrrAB 的基因。RNA 测序和比较分析确定了 30 多个 SrrAB 调节基因，这些基因可能对类阴道条件下（尤其是氧胁迫条件下）的适应性非常重要。这些发现强调了有氧呼吸、杆菌硫醇生物合成、唾液酸分解和转录调控等支持 MRSA 在阴道中竞争适应性的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.