Document Type
Article
Publication Title
bioRxiv
Abstract
Streptococcus pneumoniae (Spn) resides in the nasopharynx where it can disseminate to cause disease. One key Spn 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 Spn was present in nasal lavage elutes collected from asymptomatically colonized mice at levels ∼10-fold higher that its isogenic PspA-deficient mutant (ΔpspA). Wildtype Spn also formed aggregates in mucosal secretions composed of sloughed epithelial cells and hundreds of pneumococci, whereas ΔpspA did not. Spn 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 Spn in saline containing mGAPDH also enhanced tolerance to desiccation, but only for wildtype Spn. mGAPDH was sufficient to cause low-level aggregation of wildtype Spn but not ΔpspA. 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 Spn 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.
DOI
https://doi.org/10.1101/2023.09.27.559802
Publication Date
9-30-2023
PubMed ID
PMID: 37808718; PMCID: PMC10557681
College or School
School of Medicine
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Supplemental Associated Link
https://www.biorxiv.org/content/10.1101/2023.09.27.559802v2
Recommended Citation
Lane JR, Tata M, Yasmin R, Im H, Briles DE, Orihuela CJ. PspA-mediated aggregation protects Streptococcus pneumoniae against desiccation on fomites. bioRxiv [Preprint]. 2023 Sep 30:2023.09.27.559802. doi: 10.1101/2023.09.27.559802. PMID: 37808718; PMCID: PMC10557681.
Comments
2023/2024 APC Fund Awardee:
Dr. Carlos Orihuela, Professor
Heersink School of Medicine
Award Amount: $1,500.00