Division of Infectious Diseases, Department of Pediatrics, McGovern Medical School, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
Division of Infectious Diseases, Department of Pediatrics, McGovern Medical School, University of Texas Health Sciences Center at Houston, Houston, Texas, USA
Infect Immun. 2020 Mar 23;88(4). doi: 10.1128/IAI.00709-19.
(group A [GAS]) is a human pathogen responsible for a wide range of diseases. Asymptomatic carriage of GAS in the human pharynx is commonplace and a potential reservoir for GAS transmission. Early studies showed that GAS transmission correlated with high bacterial burdens during the acute symptomatic phase of the disease. Human studies and the nonhuman primate model are generally impractical for investigation of the bacterial mechanisms contributing to GAS transmission and persistence. To address this gap, we adapted an infant mouse model of pneumococcal colonization and transmission to investigate factors that influence GAS transmission and persistence. The model recapitulated the direct correlation between GAS burden and transmission during the acute phase of infection observed in humans and nonhuman primates. Furthermore, our results indicate that the ratio of colonized to uncolonized hosts influences the rates of GAS transmission and persistence. We used the model to test the hypothesis that capsule production influences GAS transmission and persistence in a strain-dependent manner. We detected significant differences in rates of transmission and persistence between capsule-positive () and capsule-negative () GAS strains. Capsule was associated with higher levels of GAS shedding, independent of the strain background. In contrast to the capsule-positive strain, restoring capsule production in GAS did not increase transmissibility, and the absence of capsule enhanced persistence only in the capsule-negative () strain background. These data suggest that strain background (capsule positive versus capsule negative) influences the effect of capsule in GAS transmission and persistence and that as-yet-undefined factors are required for the transmission of capsule-negative types.
(group A [GAS]) 是一种人类病原体,可导致多种疾病。无症状携带 GAS 是人类咽部的常见现象,也是 GAS 传播的潜在储库。早期研究表明,GAS 传播与疾病急性症状期的高细菌负荷相关。由于人类研究和非人类灵长类动物模型通常不适合研究导致 GAS 传播和持续存在的细菌机制,因此通常采用这些方法。为了解决这一差距,我们采用了一种肺炎球菌定植和传播的婴儿小鼠模型来研究影响 GAS 传播和持续存在的因素。该模型再现了人类和非人类灵长类动物感染急性期观察到的 GAS 负荷与传播之间的直接相关性。此外,我们的结果表明,定植宿主与未定植宿主的比例影响 GAS 传播和持续存在的速度。我们使用该模型来检验以下假设,即荚膜产生以菌株依赖性方式影响 GAS 传播和持续存在。我们检测到荚膜阳性()和荚膜阴性()GAS 菌株之间在传播和持续存在方面存在显著差异。荚膜与 GAS 脱落水平的升高独立相关,而与菌株背景无关。与荚膜阳性菌株不同,荚膜缺失的 GAS 恢复荚膜产生并不会增加传染性,而荚膜缺失仅增强荚膜阴性()菌株背景下的持续性。这些数据表明,菌株背景(荚膜阳性与荚膜阴性)影响荚膜在 GAS 传播和持续存在中的作用,并且荚膜阴性 型的传播需要尚未确定的因素。