PspA-mediated aggregation protects against desiccation on fomites.

() resides in the nasopharynx where it can disseminate to cause disease. One key virulence factor is pneumococcal surface protein A (PspA), which promotes survival by blocking the antimicrobial peptide lactoferricin. PspA has also been shown to mediate attachment to dying epithelial cells in the lower airway due to its binding of cell surface-bound mammalian (m)GAPDH. Importantly, the role of PspA during colonization is not well understood. Wildtype was present in nasal lavage elutes collected from asymptomatically colonized mice at levels ~10-fold higher that its isogenic PspA-deficient mutant (Δ). Wildtype also formed aggregates in mucosal secretions composed of sloughed epithelial cells and hundreds of pneumococci, whereas Δ did not. within the center of these aggregates better survived prolonged desiccation on fomites than individual pneumococci and were capable of infecting naïve mice, indicating PspA-mediated aggregation conferred a survival/transmission advantage. Incubation of in saline containing mGAPDH also enhanced tolerance to desiccation, but only for wildtype . mGAPDH was sufficient to cause low-level aggregation of wildtype but not Δ. In strain WU2, the subdomain of PspA responsible for binding GAPDH (aa230-281) is ensconced within the lactoferrin (LF)-binding domain (aa167-288). We observed that LF inhibited GAPDH-mediated aggregation and desiccation tolerance. Using surface plasmon resonance, we determined that forms multimeric complexes of PspA-GAPDH-LF on its surface and that LF dislodges GAPDH. Our findings have important implications regarding pneumococcal colonization/transmission processes and ongoing PspA-focused immunization efforts for this deadly pathogen.