Streptococcus pyogenes manipulates host immunity via the Rgg2/3 quorum sensing system

摘要

ABSTRACT Group A Streptococcus (GAS) is an obligate human pathogen that causes 600 million infections annually, ranging from superficial to severe and invasive. Interestingly, GAS can also asymptomatically colonize up to 30% of children. Because the reservoir for this bacterium is exclusively humans, a better understanding of mechanisms promoting the asymptomatic lifestyle of GAS can help control the persistence of this ubiquitous bacterium in the population. Like many other bacterial species, GAS utilizes chemical communication, or quorum sensing (QS) systems, to genetically coordinate behaviors across a population. Our lab has characterized the Rgg2/3 QS system and has shown that it promotes phenotypes indicative of cell surface alterations, including lysozyme resistance and biofilm formation. Our preliminary experiments show that Rgg2/3 activation also alters the host response in vitro, resulting in decreased macrophage pro-inflammatory cytokine responses, and in vivo, resulting in prolonged mouse nasopharyngeal colonization. This proposal seeks to test the hypothesis that GAS utilizes Rgg2/3 QS-mediated modifications to alter interactions with the host. We will examine the implications of these modifications on the adaptive and innate immune responses to GAS, and we will determine what altered GAS surface molecules contribute to this modulation. Understanding the role of QS in manipulating immune responses will provide additional support for developing future strategies to combat infection.