McCutcheon Cole R, Pell Macy E, Gaddy Jennifer A, Aronoff David M, Petroff Margaret G, Manning Shannon D
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, United States.
Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Front Microbiol. 2021 Nov 22;12:770499. doi: 10.3389/fmicb.2021.770499. eCollection 2021.
Although the neonatal and fetal pathogen Group B (GBS) asymptomatically colonizes the vaginal tract of ∼30% of pregnant women, only a fraction of their offspring develops invasive disease. We and others have postulated that these dimorphic clinical phenotypes are driven by strain variability; however, the bacterial factors that promote these divergent clinical phenotypes remain unclear. It was previously shown that GBS produces membrane vesicles (MVs) that contain active virulence factors capable of inducing adverse pregnancy outcomes. Because the relationship between strain variation and vesicle composition or production is unknown, we sought to quantify MV production and examine the protein composition, using label-free proteomics on MVs produced by diverse clinical GBS strains representing three phylogenetically distinct lineages. We found that MV production varied across strains, with certain strains displaying nearly twofold increases in production relative to others. Hierarchical clustering and principal component analysis of the proteomes revealed that MV composition is lineage-dependent but independent of clinical phenotype. Multiple proteins that contribute to virulence or immunomodulation, including hyaluronidase, C5a peptidase, and sialidases, were differentially abundant in MVs, and were partially responsible for this divergence. Together, these data indicate that production and composition of GBS MVs vary in a strain-dependent manner, suggesting that MVs have lineage-specific functions relating to virulence. Such differences may contribute to variation in clinical phenotypes observed among individuals infected with GBS strains representing distinct lineages.
尽管新生儿和胎儿病原体B族链球菌（GBS）无症状地定植于约30%孕妇的阴道生殖道，但只有一小部分其后代会发生侵袭性疾病。我们和其他人推测这些双态临床表型是由菌株变异性驱动的；然而，促进这些不同临床表型的细菌因素仍不清楚。先前已表明GBS会产生膜泡（MVs），其含有能够诱导不良妊娠结局的活性毒力因子。由于菌株变异与囊泡组成或产生之间的关系尚不清楚，我们试图对MV产生进行定量，并使用无标记蛋白质组学研究由代表三个系统发育不同谱系的多种临床GBS菌株产生的MVs的蛋白质组成。我们发现MV产生在不同菌株间存在差异，某些菌株的产生量相对于其他菌株增加了近两倍。蛋白质组的层次聚类和主成分分析表明，MV组成依赖于谱系，但与临床表型无关。多种有助于毒力或免疫调节的蛋白质，包括透明质酸酶、C5a肽酶和唾液酸酶，在MVs中的丰度存在差异，并且部分导致了这种差异。总之，这些数据表明GBS MVs的产生和组成以菌株依赖的方式变化，表明MVs具有与毒力相关的谱系特异性功能。这种差异可能导致在感染代表不同谱系的GBS菌株的个体中观察到的临床表型的变化。
