YvqE and CovRS of Group A Streptococcus Play a Pivotal Role in Viability and Phenotypic Adaptations to Multiple Environmental Stresses

Streptococcus pyogenes (group A Streptococcus, or GAS) is a human pathogen that causes a wide range of diseases. For successful colonization within a variety of host niches, GAS utilizes TCSs to sense and respond to environmental changes and adapts its pathogenic traits accordingly; however, many GAS TCSs and their interactions remain uncharacterized. Here, we elucidated the roles of a poorly characterized TCS, YvqEC, and a well-studied TCS, CovRS, in 2 different GAS strain SSI-1 and JRS4, respectively. Deletion of yvqE and yvqC in JRS4 resulted in lower cell viability and abnormality of cell division when compared to the wild-type strain under standard culture conditions, demonstrating an important role for YvqEC. Furthermore, a double-deletion of yvqEC and covRS in SSI-1 and JRS4 resulted in a significantly impaired ability to survive under various stress conditions, as well as an increased sensitivity to cell wall-targeting antibiotics compared to that observed in either single mutant or wild-type strains suggesting synergistic interactions. Our findings provide new insights into the impact of poorly characterized TCS (YvqEC) and potential synergistic interactions between YvqEC and CovRS and reveal their potential role as novel therapeutic targets against GAS infection.