Salmonella Typhimurium PgtE is an essential arsenal to defend against the host resident antimicrobial peptides

• Published in: Microbiological research 2023-06, Vol.271, p.127351-127351, Article 127351
• Main Authors: Chatterjee, Ritika, Chowdhury, Atish Roy, Nair, Abhilash Vijay, Hajra, Dipasree, Kar, Arpita, Datey, Akshay, Shankar, Santhosh, Mishra, Rishi Kumar, Chandra, Nagasuma, Chakravortty, Dipshikha
• Format: Article
• Language: English
• Subjects: Animals; Antimicrobial Peptides; Antimicrobial peptides (AMPs); Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bactericidal/ permeability-increasing protein (BPI); Endopeptidases - genetics; Endopeptidases - metabolism; Humans; Macrophages; Mice; Mice, Inbred C57BL; Omptins; Outer membrane protease; Peptide Hydrolases - genetics; Peptide Hydrolases - metabolism; Salmonella Typhimurium; Salmonella typhimurium - metabolism
• ISSN: 0944-5013; 1618-0623
• DOI: 10.1016/j.micres.2023.127351

Salmonella enterica serovar Typhimurium is a common cause of gastroenteritis in humans and occasionally causes systemic infection. Salmonella's ability to survive and replicate within macrophages is an important characteristic during systemic infection. The outer membrane protease PgtE of S. enterica is a member of the Omptin family of outer membrane aspartate proteases which has well-characterized proteolytic activities in-vitro against a wide range of physiologically relevant substrates. However, no study has been done so far that draws a direct correlation between these in-vitro observations and the biology of the pathogen in-vivo. The main goals of this study were to characterize the pathogenesis-associated functions of pgtE and study its role in the intracellular survival and in-vivo virulence of Salmonella Typhimurium. Our study elucidated a possible role of Salmonella Typhimurium pgtE in combating host antimicrobial peptide- bactericidal/ permeability increasing protein (BPI) to survive in human macrophages. The pgtE-deficient strain of Salmonella showed attenuated proliferation and enhanced colocalization with BPI in U937 and Thp1 cells. In the presence of polymixin B, the attenuated in-vitro survival of STM ΔpgtE suggested a role of PgtE against the antimicrobial peptides. In addition, our study revealed that compared to the wild type Salmonella, the pgtE mutant is replication-deficient in C57BL/6 mice. Further, we showed that PgtE interacts directly with several antimicrobial peptides (AMPs) in the host gut. This gives the pathogen a survival advantage and helps to mount a successful infection in the host