The ClpXP Protease Contributes to Staphylococcus aureus Pneumonia

• Published in: The Journal of infectious diseases Vol. 222; no. 8; pp. 1400 - 1404
• Main Authors: Kim, Gyu-Lee, Akoolo, Lavoisier, Parker, Dane
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15-10-2020
• Subjects: Animal models; Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Disease Models, Animal; Endopeptidase Clp - genetics; Endopeptidase Clp - metabolism; Female; Host-Pathogen Interactions; Inflammation; Major and Brief Reports; Male; Mice; Mice, Inbred C57BL; Microbial Viability; Mutation; Neutrophils - immunology; Pathogenesis; Penicillin; Pneumonia; Pneumonia, Staphylococcal - immunology; Pneumonia, Staphylococcal - microbiology; Pneumonia, Staphylococcal - pathology; Protein turnover; Proteinase; Respiratory tract; Staphylococcus aureus; Staphylococcus aureus - enzymology; Staphylococcus aureus - genetics; Staphylococcus aureus - pathogenicity; lung; ClpX; host–pathogen interactions; pneumonia; inflammation; ClpP; ClpXP; neutrophils; Staphylococcus aureus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiaa251

Abstract
Staphylococcus
aureus is a leading cause of pneumonia. We show here that the ClpXP protease involved in protein turnover is important for pathogenesis in a murine model of acute pneumonia. Staphylococcus aureus lacking this protease is attenuated in vivo, being rapidly cleared from the airway and leading to decreased immune cell influx and inflammation. Characterization of defined mutations in vitro identified defects in intracellular survival and protection against neutrophil killing. Our results further expand on what is known about ClpXP in the pathogenesis of S. aureus to include the respiratory tract.
This study shows that the ClpXP protease of Staphylococcus aureus is important for acute pneumonia. Mice display improved clearance and reduced inflammation, whereas S. aureus mutants are more susceptible to host cell killing.