Streptococcus pneumoniae secretion chaperones PrsA, SlrA, and HtrA are required for competence, antibiotic resistance, colonization, and invasive disease.

Streptococcus pneumoniae is a Gram-positive bacterium and a significant health threat with the populations most at risk being children, the elderly, and the immuno-compromised. To colonize and transition into an invasive infectious organism, S. pneumoniae secretes virulence factors that are translocated across the bacterial membrane and destined for surface exposure, attachment to the cell wall, or secretion into the host. The surface exposed protein chaperones PrsA, SlrA, and HtrA facilitate S. pneumoniae protein secretion; however, the distinct roles contributed by each of these secretion chaperones have not been well defined. Tandem Mass-Tagged Mass Spectrometry and virulence, adhesion, competence, and cell wall integrity assays were used to interrogate the individual and collective contributions of PrsA, SlrA, and HtrA to multiple aspects of S. pneumoniae physiology and virulence. PrsA, SlrA, and HtrA were found to play critical roles in S. pneumoniae host cell infection and competence, and the absence of each of these secretion chaperones significantly altered the S. pneumoniae secretome in distinct ways. PrsA and SlrA were additionally found to contribute to cell wall assembly and resistance to cell wall-active antimicrobials and were important for enabling S. pneumoniae host cell adhesion during colonization and invasive infection. These findings serve to further illustrate the pivotal contributions of PrsA, SlrA, and HtrA to S. pneumoniae protein secretion and virulence.