# Characterization of pneumococcal secretion chaperones required for virulence

> **NIH NIH R00** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $249,000

## Abstract

Characterization of pneumococcal secretion chaperones required for virulence
Streptococcus pneumoniae is a Gram-positive pathogen that spreads through airborne droplets and
colonizes the human nasopharynx where asymptomatic carriage is a prerequisite for invasive disease. S.
pneumoniae is a significant health threat, globally causing more deaths than any other infectious disease. In
order for S. pneumoniae to colonize and transition into an invasive infection, the bacterium relies on the
elaboration of many virulence factors that are translocated across the bacterial membrane and destined for
attachment to the cell wall or secretion into the host. Despite the pivotal importance of secreted proteins in
bacterial pathogenesis, little is known about the mechanisms that regulate protein activity following
membrane translocation in Gram-positive bacteria. Our laboratory identified the secretion chaperone PrsA2
in the Gram-positive bacterium Listeria monocytogenes (Lm) which is essential for virulence, and appears
to be required for the proper folding and secretion of a number of virulence factors. My research has
focused on the two prsA alleles of Lm: prsA1 and prsA2 that both have peptidyl-prolyl isomerase (PPIase)
domains in addition to a foldase domain. We solved the crystal structure of Lm PrsA1 and I deciphered how
structural features of PrsA1 and PrsA2 contribute to PPIase and chaperone activities in the organism. I
have also determined that some PrsA activities are broadly conserved between species while others are
highly specific. We recently solved the crystal structure of S. pneumoniae PrsA and I will use this structure
to accomplish some of my research objectives to define the mechanisms that govern activity of secreted
virulence factors in S. pneumoniae. Central to S. pneumoniae protein secretion are the surface exposed
proteins: PrsA chaperone, HtrA protease/chaperone, and SlrA PPIase. I hypothesize that during host
infection, S. pneumoniae PrsA, HtrA, and SlrA regulate proper folding, stabilization, and activity of secreted
proteins which contribute to colonization and pathogenesis. In addition, surface exposed PrsA, HtrA and
SlrA are potentially attractive drug targets because inhibition may increase antibiotic susceptibility while
reducing virulence factor secretion. To implement my research objectives during the mentored K99 phase, I
will work closely with my mentor Dr. Nancy Freitag who is an expert in the field of Gram-positive
pathogenesis and my collaborator Dr. Don Morrison who is an expert in the field of S. pneumoniae
molecular genetics and biology. By taking advantage of advances in proteomic analytical techniques, this
award will enable me to establish a research program with the long-term objective of deciphering the
mechanisms of virulence factor secretion and regulation in the Gram-positive pathogen S. pneumoniae
which will also likely have broad relevance to other important Gram-positive pathogens.

## Key facts

- **NIH application ID:** 10046756
- **Project number:** 4R00AI128029-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Laty Adriella Cahoon
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046756

## Citation

> US National Institutes of Health, RePORTER application 10046756, Characterization of pneumococcal secretion chaperones required for virulence (4R00AI128029-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046756. Licensed CC0.

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