Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice.
Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice.
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DOI：
10.1128/spectrum.01058-21
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发表时间：
2021-12-22
影响因子：
3.7
通讯作者：
Patras KA
中科院分区：
文献类型：
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作者：
Ballard MB;Mercado-Evans V;Marunde MG;Nwanosike H;Zulk J;Patras KA
革兰氏阳性病原体B族链球菌（GBS）是新生儿细菌感染、早产和死产的主要原因。虽然母体GBS阴道定植是GBS相关不良出生结局的一个危险因素，但促进GBS阴道持续存在的机制尚未完全确定。GBS具有广泛保守的小分子CAMP因子，其在金黄色葡萄球菌鞘磷脂酶C存在下是共溶血性的。虽然临床实验室通常使用这种共溶血反应来识别GBS，但CAMP因子对GBS阴道持续性的贡献尚不清楚。使用体外生物膜、永生化人阴道上皮VK2细胞的粘附和侵袭试验以及GBS阴道定植的小鼠模型，我们使用GBS菌株COH1及其同基因cAMP缺陷突变体（Δcfb）检测了cAMP因子的贡献。我们没有发现任何证据表明CAMP因子参与GBS生物膜的形成，或在存在或不存在S.金黄色。此外，在小鼠定植模型中，COH 1和Δcfb菌株之间的阴道负荷或持久性无差异。总之，我们使用体外人细胞系和小鼠模型的结果不支持CAMP因子在促进GBS阴道定植中的关键作用。重要性B族链球菌（GBS）仍然是孕妇及其新生儿的普遍病原体。对GBS阳性母亲进行母体筛查和产时抗生素预防减少了GBS新生儿疾病，但没有消除GBS新生儿疾病，也没有影响GBS相关的早产或死产。此外，这种抗生素暴露与对母体和新生儿微生物群的不良影响有关。确定对母体阴道定植重要的关键GBS因素将促进开发更具针对性的抗生素治疗替代疗法。在这里，我们调查了一个广泛保守的GBS决定簇，CAMP因子，GBS阴道定植的贡献，并发现CAMP因子是不太可能的生物学目标，以控制产妇GBS定植。
The Gram-positive pathogen group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections, preterm birth, and stillbirth. Although maternal GBS vaginal colonization is a risk factor for GBS-associated adverse birth outcomes, mechanisms promoting GBS vaginal persistence are not fully defined. GBS possesses a broadly conserved small molecule, CAMP factor, that is co-hemolytic in the presence of Staphylococcus aureus sphingomyelinase C. While this co-hemolytic reaction is commonly used by clinical laboratories to identify GBS, the contribution of CAMP factor to GBS vaginal persistence is unknown. Using in vitro biofilm, adherence and invasion assays with immortalized human vaginal epithelial VK2 cells, and a mouse model of GBS vaginal colonization, we tested the contribution of CAMP factor using GBS strain COH1 and its isogenic CAMP-deficient mutant (Δcfb). We found no evidence for CAMP factor involvement in GBS biofilm formation, or adherence, invasion, or cytotoxicity toward VK2 cells in the presence or absence of S. aureus. Additionally, there was no difference in vaginal burdens or persistence between COH1 and Δcfb strains in a murine colonization model. In summary, our results using in vitro human cell lines and murine models do not support a critical role for CAMP factor in promoting GBS vaginal colonization. IMPORTANCE Group B Streptococcus (GBS) remains a pervasive pathogen for pregnant women and their newborns. Maternal screening and intrapartum antibiotic prophylaxis to GBS-positive mothers have reduced, but not eliminated GBS neonatal disease, and have not impacted GBS-associated preterm birth or stillbirth. Additionally, this antibiotic exposure is associated with adverse effects on the maternal and neonatal microbiota. Identifying key GBS factors important for maternal vaginal colonization will foster development of more targeted, alternative therapies to antibiotic treatment. Here, we investigate the contribution of a broadly conserved GBS determinant, CAMP factor, to GBS vaginal colonization and find that CAMP factor is unlikely to be a biological target to control maternal GBS colonization.