Shabayek Sarah, Bauer Richard, Mauerer Stefanie, Mizaikoff Boris, Spellerberg Barbara
Institute of Medical Microbiology and Hygiene, University of Ulm, Ulm, Germany.
Microbiology and Immunology Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Mol Microbiol. 2016 May;100(4):589-606. doi: 10.1111/mmi.13335. Epub 2016 Feb 29.
Streptococcus agalactiae or Group B Streptococcus (GBS) is a commensal bacterium of the human gastrointestinal and urogenital tracts as well as a leading cause of neonatal sepsis, pneumonia and meningitis. Maternal vaginal carriage is the main source for GBS transmission and thus the most important risk factor for neonatal disease. Several studies in eukaryotes identified a group of proteins natural resistance-associated macrophage protein (NRAMP) that function as divalent cation transporters for Fe(2+) and Mn(2+) and confer on macrophages the ability to control replication of bacterial pathogens. Genome sequencing predicted potential NRAMP homologues in several prokaryotes. Here we describe for the first time, a pH-regulated NRAMP Mn(2+) /Fe(2+) transporter in GBS, designated MntH, which confers resistance to reactive oxygen species (ROS) and is crucial for bacterial growth and survival under low pH conditions. Our investigation implicates MntH as an important colonization determinant for GBS in the maternal vagina as it helps bacteria to adapt to the harsh acidic environment, facilitates bacterial adherence, contributes to the coexistence with the vaginal microbiota and plays a role in GBS intracellular survival inside macrophages.
无乳链球菌或B族链球菌(GBS)是人类胃肠道和泌尿生殖道的共生菌,也是新生儿败血症、肺炎和脑膜炎的主要病因。孕妇阴道携带是GBS传播的主要来源,因此也是新生儿疾病最重要的危险因素。在真核生物中的几项研究鉴定出一组天然抗性相关巨噬细胞蛋白(NRAMP),其作为Fe(2+)和Mn(2+)的二价阳离子转运蛋白,赋予巨噬细胞控制细菌病原体复制的能力。基因组测序预测了几种原核生物中潜在的NRAMP同源物。在此我们首次描述了GBS中一种受pH调节的NRAMP Mn(2+)/Fe(2+)转运蛋白,命名为MntH,它赋予对活性氧(ROS)的抗性,并且在低pH条件下对细菌生长和存活至关重要。我们的研究表明MntH是GBS在孕妇阴道中重要的定植决定因素,因为它帮助细菌适应恶劣的酸性环境,促进细菌黏附,有助于与阴道微生物群共存,并在GBS在巨噬细胞内的存活中发挥作用。