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Acinetobacter baumannii (A. baumannii) is characterized by a high prevalence of drug resistance; how to effectively treat it is still a major clinical challenge. Our previous experiments confirmed that ompA, which is one of the most well-characterized virulence factors, may be dependent on the caspase-1 pathway-stimulated expression of NLRP3 inflammasome to enhance inflammation. TLRs (i.e., TLR2, etc.) is the initiating signal for NLRP3 inflammasome activation; how it relates to ompA in its underlying pathogenic mechanism is not clear. In this study, we proofed that ompA promoted NLRP3 inflammasome activation while the TLR2-NF-κB pathway was also activated after A. baumannii infection. Additionally, the expression of NLRP3 inflammasome-associated proteins and genes was inhibited by silencing TLR2 and NLRP3. This indicated that ompA might depend on the TLR2-NF-κB pathway to assemble and activate the NLRP3 inflammasome. OmpA promoted the assembly of the NLRP3 inflammasome through the TLR2-NF-κB pathway and inhibited the degradation of caspase-1 by the proteasome so that a large number of mature IL-1β/IL-18 and other proinflammatory factors were released extracellularly to enhance the body's inflammatory response. Taken together, the results of the joint pre-study confirmed a novel TLR2-NF-κB/NLRP3/caspase-1-modulated mechanism underpinning ompA activity, the NLRP3 inflammasome pathway may be as a potential immunomodulatory target against A. baumannii infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing fnancial interests or personal relationships that could have appeared to infuence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acinetobacter baumannii (A. baumannii), one of the major pathogens that causes severe nosocomial infections, is characterised by a high prevalence of drug resistance. It has been reported that A. baumannii triggers the NOD-like receptor 3 (NLRP3) inflammasome, but the role of its virulence-related outer membrane protein A (ompA) remains unclear. Therefore, this study aimed to explore the effects of ompA on the NLRP3 inflammasome and its underlying molecular mechanisms. Results showed that ompA enhanced inflammatory damage, which was reduced as a result of knockout of the ompA gene. Additionally, ompA-stimulated expression of NLRP3 inflammasome was significantly blocked by silencing caspase-1, but activation of NLRP3 inflammasome was not altered after silencing ASC; this indicated that ompA was dependent on the caspase-1 pathway to activate the inflammatory response. Simultaneously, the wild-type (WT) strains triggered NLRP3 inflammasome after inhibition of caspase-1 degradation by proteasome inhibitor MG-132, aggravating tissue damage. These findings indicated that ompA may be dependent on the caspase-1 pathway to enhance inflammation and exacerbate tissue damage. Taken together, these results confirmed a novel capsase-1-modulated mechanism underpinning ompA activity, which further reveals the NLRP3 inflammasome pathway as a potential immunomodulatory target against A. baumannii infections., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Outer membrane protein A (OmpA) of Acinetobacter baumannii (A. baumannii) is associated with autophagy, which plays an important role in its pathogenicity. However, its exact pathophysiological role in the process of lung tissue cell autophagy remains unclear. In this study, animal and cell infection models were established by wild A. baumannii strain and An OmpA knockout mutant (OmpA-/- A. baumannii) strain. The expression levels of markers autophagy, histological change, cell viability and protein expression levels of inflammatory cytokines were examined. OmpA-/-A. baumannii was successfully constructed. The capacities of bacterial adhesion and invasion to host cells increased more obviously in the AB group and the AB + Rapa group than in the OmpA-/- AB group and AB + CQ group. The AB group and AB + Rapa group could produce double membrane vacuoles, endoplasmic reticulum dilation, mitochondrial ridge rupture, and mitochondrial vacuoles. OmpA could lead to increased LC3, AMPK, and PAMPK protein release, and decreased levels of P62, mTOR and pmTOR proteins in vivo and in vitro. OmpA caused lung pathology and the release of inflammatory cytokines. A. baumannii OmpA promotes autophagy in lung cells through the mTOR signalling pathway, which increases the bacterial colonization ability in the double-layer membrane autophagosome formed by the autophagy reaction to escape the clearance of bacteria by the host, promote the release of inflammatory mediators and aggravate the damage to the host., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)