Lyon Laurie M, Marroquin Stephanie M, Thorstenson John C, Joyce Luke R, Fuentes Ernesto J, Doran Kelly S, Horswill Alexander R
University of Colorado Anschutz Medical Campus, Department of Immunology and Microbiology, Aurora, CO, USA.
Department of Biochemistry and Molecular Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Cell Rep. 2025 Mar 25;44(3):115421. doi: 10.1016/j.celrep.2025.115421. Epub 2025 Mar 13.
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.
耐甲氧西林金黄色葡萄球菌（MRSA）是一种机会致病菌，可在包括鼻腔、皮肤和阴道在内的身体各个部位定植。在怀孕期间，定植可导致生态失调、不良妊娠结局和侵袭性疾病。为了鉴定有助于MRSA在阴道中生存适应的基因，我们使用阴道定植的小鼠模型进行了转座子测序（Tn-seq），鉴定出超过250个条件必需基因。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、唾液酸分解代谢酶NanE和呼吸葡萄球菌调节因子SrrAB的基因。RNA测序和比较分析确定了超过30个SrrAB调节的基因，这些基因可能对在类似阴道环境中的生存适应很重要；特别是在氧应激条件下。这些发现突出了有氧呼吸、杆菌硫醇生物合成、唾液酸分解代谢和转录调节等途径，这些途径支持MRSA在阴道中的竞争适应性。
