Host Protease Activity on Bacterial Pathogens Promotes Complement and Antibiotic-Directed Killing

• Published in: Pathogens (Basel) Vol. 10; no. 11; p. 1506
• Main Authors: Chen, Shaorong, Zhang, Dongmei, Roberts, Alexandria-Jade, Lu, Hsueh-Chung, Cannon, Carolyn L., Qin, Qing-Ming, de Figueiredo, Paul
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 18-11-2021; MDPI
• Subjects: Antibiotics; Bacteria; Bacterial infections; bacterial pathogens; Communication; Complement; Complement system; Cytotoxicity; Drug resistance; Elastase; host complement system; host immune system; Hypotheses; Immune system; Leukocytes (neutrophilic); multidrug resistant bacteria; Pathogens; Protease; protease neutrophil elastase; Proteinase; Pseudomonas aeruginosa; Vaccines
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens10111506

Our understanding of how the host immune system thwarts bacterial evasive mechanisms remains incomplete. Here, we show that host protease neutrophil elastase acts on Acinetobacter baumannii and Pseudomonas aeruginosa to destroy factors that prevent serum-associated, complement-directed killing. The protease activity also enhances bacterial susceptibility to antibiotics in sera. These findings implicate a new paradigm where host protease activity on bacteria acts combinatorially with the host complement system and antibiotics to defeat bacterial pathogens.