# Staphylococcus aureus type VII secretion mediated immune evasion

> **NIH NIH F32** · UNIVERSITY OF CHICAGO · 2020 · $67,446

## Abstract

ABSTRACT
Staphylococcus aureus colonizes the nasopharynx and gastrointestinal tract of humans, which
represents a key risk factor for invasive diseases such as skin and bloodstream infections.
Hallmarks of S. aureus are the persistent colonization of about one third of the human
population and the ability to cause reiterative infections without eliciting protective immune
responses. Earlier work reported that the type VII secretion system (ESS or T7bSS) is crucial
for the pathogenesis of S. aureus bloodstream infections and staphylococcal escape from T cell
responses. During infection, S. aureus activate dendritic cells to secrete IL-12 (p40/p70),
thereby compromising the induction of adaptive immune responses due to IL-12 skewing of g-
interferon-producing TH1 cells, which impede TH2 polarization and the host's ability to produce
pathogen-specific antibodies. Earlier work identified genes (esaA, essA, essB and essC), whose
products function as core components of the T7bSS in the staphylococcal membrane, which
associate with mobile proteins (EsxA, EsxB, EsxC, EsxD and EssD) that travel the ESS
pathway. One of these secretion substrates, EssD comprises a nuclease domain that cleaves
DNA and promotes IL-12 secretion in myeloid cells in vivo and in vitro. We also identified new
genes whose products are essential for ESS secretion. The product of essH is secreted via the
Sec pathway and exhibits peptidoglycan hydrolase activity required for the assembly of the ESS
pathway. Genes whose products are members of the DUF5079 and DUF5080 family represent
membrane proteins that contribute to T7bSS pathway. Our proposal seeks to investigate the
trafficking of the EssH effector into myeloid cells, to locate its nuclease activity in subcellular
compartments of myeloid cells and to identify host signaling components required for IL-12
secretion. Other work will examine the mechanistic contributions of EssH, DUF5079 and
DUF5080 proteins towards assembly and secretion of the T7bSS. Last, we will study S. aureus
WU1, an ST88 isolate that adapted to persistently colonize the nasopharynx and
gastrointestinal tract of mice and to cause spontaneous invasive diseases. Our experiments will
explore the contributions of the ESS pathway during S. aureus WU1 persistent colonization and
invasive disease in mice.

## Key facts

- **NIH application ID:** 9962298
- **Project number:** 5F32AI140643-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Maksym Bobrovskyy
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2018-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962298

## Citation

> US National Institutes of Health, RePORTER application 9962298, Staphylococcus aureus type VII secretion mediated immune evasion (5F32AI140643-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9962298. Licensed CC0.

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