Pec 1 of Pseudomonas aeruginosa Inhibits Bacterial Clearance of Host by Blocking Autophagy in Macrophages

ACS Infect Dis. 2024 Aug 9;10(8):2741-2754. doi: 10.1021/acsinfecdis.4c00096. Epub 2024 Jul 24.

Abstract

Pseudomonas aeruginosa (P. aeruginosa), a common opportunistic pathogen, is highly prone to chronic infection and is almost impossible to eradicate, especially attributed to virulence factors and adaptive mutations. In the present study, pseudomonas effector candidate 1 (Pec 1), a novel virulence factor of P. aeruginosa, was investigated, which inhibited bacterial clearance by the host and aggravated lung injury. Further, it demonstrated that Pec 1 inhibited miR-155 via suppressing integrin β3 expression, thereby activating PI3K-AKT-mTOR and inhibiting autophagy in macrophages. Additionally, the identification of Pec 1 in sputum was related to the bacterial load and assisted in rapid diagnosis of P. aeruginosa infection. This finding underlined the importance of Pec 1 in the pathogenesis of P. aeruginosa infection and indicated that Pec 1 could be a vital independent virulence factor during chronic infection with P. aeruginosa, providing new insights in rapid diagnosis, therapeutic targets, and vaccine antigens of P. aeruginosa infection.

Keywords: Pseudomonas aeruginosa; autophagy; diagnosis; macrophages; pseudomonas effector candidate 1.

MeSH terms

  • Animals
  • Autophagy*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Macrophages* / microbiology
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pseudomonas Infections* / immunology
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa* / pathogenicity
  • Pseudomonas aeruginosa* / physiology
  • TOR Serine-Threonine Kinases / metabolism
  • Virulence Factors* / genetics
  • Virulence Factors* / metabolism

Substances

  • Virulence Factors
  • MicroRNAs
  • Bacterial Proteins
  • TOR Serine-Threonine Kinases
  • Phosphatidylinositol 3-Kinases