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

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.