Journal
INFECTION AND IMMUNITY
Volume 87, Issue 12, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00695-19
Keywords
ExsA; ImpA; Pseudomonas aeruginosa; type III secretion system; macrophages; phagocytosis
Categories
Funding
- National Key Research and Development Project of China [2017YFE0125600]
- National Science Foundation of China [31670130, 31970680, 31870130, 81670766]
- Tianjin Municipal Science and Technology Commission, China [19JCYBJC24700]
- Fundamental Research Funds for the Central Universities, Nankai University [63191521, 63191121]
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Pseudomonas aeruginosa is an opportunistic pathogenic bacterium whose type III secretion system (T3SS) plays a critical role in acute infections. Translocation of the T3SS effectors into host cells induces cytotoxicity. In addition, the T3SS promotes the intracellular growth of P. aeruginosa during host infections. The T3SS regulon genes are regulated by an AraC-type regulator, ExsA. In this study, we found that an extracellular metalloprotease encoded by impA (PA0572) is under the regulation of ExsA. An ExsA consensus binding sequence was identified upstream of the impA gene, and direct binding of the site by ExsA was demonstrated via an electrophoretic mobility shift assay. We further demonstrate that secreted ImpA cleaves the macrophage surface protein CD44, which inhibits the phagocytosis of the bacterial cells by macrophages. Combined, our results reveal a novel ExsA-regulated virulence factor that cooperatively inhibits the functions of macrophages with the T3SS.
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