Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection

Abstract

Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing serious nosocomial infections, which is considered as the most threatening Gram-negative bacteria (GNB). Outer membrane protein A (OmpA), a major component of outer membrane proteins (OMPs) in GNB, is a key virulence factor which mediates bacterial biofilm formation, eukaryotic cell infection, antibiotic resistance and immunomodulation. The characteristics of OmpA in Escherichia coli (E. coli) have been extensively studied since 1974, but only in recent years researchers started to clarify the functions of OmpA in A. baumannii. In this review, we summarized the structure and functions of OmpA in A. baumannii (AbOmpA), collected novel therapeutic strategies against it for treating A. baumannii infection, and emphasized the feasibility of using AbOmpA as a potential therapeutic target.

Keywords: A. baumannii; AbOmpA; Infection; Multidrug-resistant; Therapeutic target.

Fig. 1

Functions of OmpA in A. baumannii. a upper panel. When contacting with epithelial cells, bacteria secrets OmpA into these cells. The OmpA are able to translocate in nucleus and mitochondria, and stimulate mitochondria to release cytochrome c. Then cytochrome c promotes apoptosis inducing factor (AIF) to translocate into nucleus and finally causes apoptosis of epithelial cells. Lower panel. OmpA increases the production of nitric oxide synthase (iNOS) and surface expression of Toll-like receptor 2 (TLR2) in epithelial cells, both of which trigger host cell death. b At low concentration, OmpA activates DCs which then stimulates CD4⁺T cells to exert Th1 response, while at high concentration; OmpA kills DCs by inducing mitochondria to release ROS. c AbOmpA can arrest serum factor H in serum, causing the paralysis of complement response. d AbOmpA play a dominant role in attaching abiotic surfaces and forming biofilm matrix. e AbOmpA is a porin protein which locates in outer membrane, selectively allowing the permeation of small molecular compounds