The Potential Ability of Group A Streptococcus to Evade Lysosomal Degradation in Host Cells
Authors:Hyewon No, Cheryl Okumura, Andreas Till
Mentor:Cheryl Okumura, Biology Professor, Occidental College
Group A Streptococcus (GAS) is a bacterial pathogen known for causing a variety of infections ranging from mild pharyngitis to the invasive necrotizing fasciitis. Despite the evasive and virulent evolution of GAS that has contributed to its persistence, the defensive mechanisms employed by host cells are equally as notable. In this study, we sought to create a molecular tool to study intracellular trafficking and degradation of GAS by phagocytic cells. We created a construct using a tandem red fluorescent protein linked to a pH-sensitive green fluorescent protein (mWASABI), which upon contact with the low pH environment of the lysosomes would be degraded. We confirmed successful cloning and expression of the construct into GAS. However, to our surprise, our preliminary research involving the infection of phagocytic cells with the RFP-mWASABI expressing bacteria in combination with immunofluorescent assays indicates the failure of the GFP to degrade despite evidence of bacterial colocalization with lysosomes. Our data suggests that GAS is either disabling lysosomal acidification, thus preventing the activation of lysosomal degradative enzymes, or is capable of withstanding the low pH environment and proteolytic enzymes present in the lysosomes. These mechanisms of resistance to lysosomal degradation may further contribute to bacterial virulence and persistence. Our project continues to explore this prospect and generate data that will contribute to our overall understanding of how GAS has evolved to circumvent cellular defense mechanisms so that we can continue to develop the appropriate treatment options for GAS infections.