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Published on: May 4, 2016
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.
Abstract:
Outer membrane protein A (OmpA) plays a vital role in the interactions between Acinetobacter baumannii and host cells. Autophagy is a defense mechanism that hinders the intracellular replication of bacteria, thereby safeguarding cells against microbial infections. While it has been observed that A. baumannii triggers cellular autophagy, the precise role of its virulence protein OmpA in this process remains uncertain. In this study, we investigated the effects of A. baumannii OmpA (AbOmpA) on autophagy and explored the underlying molecular mechanisms. We found that AbOmpA exerted its autophagy-suppressive effect through inhibition of CaMKK2 phosphorylation. Compared to the wild-type strain, the ompA-deletion mutant strain displayed considerably enhanced autophagy induction, via the AMPK-ULK1 pathway. AbOmpA hindered starvation-induced autophagy, while A. baumannii-Omp33 (AbOmp33) and Escherichia coli-OmpA (EcOmpA) did not. Importantly, we confirmed that exogenous AbOmpA suppressed autophagy through the CaMKK2-AMPK-ULK1 pathway during A. baumannii infection. These findings reveal a novel mechanism for AbOmpA-mediated autophagy evasion, providing new insights into the pathogenesis of A. baumannii infection.IMPORTANCEAcinetobacter baumannii is a significant clinical pathogen notorious for causing infections in hospitals. Its outer membrane protein A acts as a virulence factor and helps the bacteria evade host defenses. Autophagy is a defense mechanism that hinders the intracellular replication of bacteria. While it has been observed that A. baumannii triggers cellular autophagy, the precise role of its AbOmpA in this process remains uncertain. Our studies demonstrate the AbOmpA of A. baumannii inhibits the cellular defense process, autophagy, through the CaMKK2-AMPK-ULK1 signaling cascade, thereby enhancing bacterial survival. This insight into how AbOmpA bypasses autophagy sheds light on A. baumannii infection's novel virulence strategy and suggests possible treatments.
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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