Acinetobacter baumannii OmpA hinders host autophagy via the CaMKK2-reliant AMPK-pathway

Kyungho Woo1,2, Dong Ho Kim1,2, Ho-Sung Park1,3,4

  • 1Department of Microbiology, School of Medicine, Chungnam National University, Daejeon, South Korea.

Mbio
|February 25, 2025
PubMed

Insights

Acinetobacter baumannii outer membrane protein A (AbOmpA) suppresses host cell autophagy, a key defense mechanism. This evasion occurs via the CaMKK2-AMPK-ULK1 pathway, aiding bacterial survival and pathogenesis.

Area of Science:

  • Microbiology
  • Cellular Biology
  • Immunology

Background:

  • Outer membrane protein A (OmpA) is crucial for *Acinetobacter baumannii* host cell interactions.
  • Autophagy is a cellular defense against microbial invasion, hindering bacterial replication.
  • The role of *A. baumannii* OmpA in modulating host autophagy remains unclear.

Purpose of the Study:

  • To investigate the impact of *Acinetobacter baumannii* OmpA (AbOmpA) on host cell autophagy.
  • To elucidate the molecular mechanisms by which AbOmpA influences autophagy.
  • To understand AbOmpA's contribution to *A. baumannii* pathogenesis.

Main Methods:

  • Investigated autophagy induction in host cells treated with *A. baumannii* and its OmpA.
  • Utilized gene deletion mutants (*ompA*-deletion) to assess autophagy levels.
  • Examined the role of the CaMKK2-AMPK-ULK1 signaling pathway in AbOmpA-mediated autophagy suppression.
  • Compared the effects of AbOmpA with other OmpA proteins (AbOmp33, EcOmpA).

Main Results:

  • AbOmpA significantly suppressed autophagy by inhibiting CaMKK2 phosphorylation.
  • An *ompA*-deletion mutant showed enhanced autophagy induction via the AMPK-ULK1 pathway.
  • AbOmpA, but not AbOmp33 or EcOmpA, inhibited starvation-induced autophagy.
  • Exogenous AbOmpA suppressed autophagy through the CaMKK2-AMPK-ULK1 pathway during infection.

Conclusions:

  • AbOmpA is a novel virulence factor that actively evades host autophagy.
  • The CaMKK2-AMPK-ULK1 pathway is a critical target for AbOmpA-mediated immune evasion.
  • Understanding this mechanism provides insights into *A. baumannii* pathogenesis and potential therapeutic strategies.

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