The Outer Membrane Proteins OmpA, CarO, and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen

Abstract

Of all the ESKAPE pathogens, carbapenem-resistant and multidrug-resistant Acinetobacter baumannii is the leading cause of hospital-acquired and ventilator-associated pneumonia. A. baumannii infections are notoriously hard to eradicate due to its propensity to rapidly acquire multitude of resistance determinants and the virulence factor cornucopia elucidated by the bacterium that help it fend off a wide range of adverse conditions imposed upon by host and environment. One such weapon in the arsenal of A. baumannii is the outer membrane protein (OMP) compendium. OMPs in A. baumannii play distinctive roles in facilitating the bacterial acclimatization to antibiotic- and host-induced stresses, albeit following entirely different mechanisms. OMPs are major immunogenic proteins in bacteria conferring bacteria host-fitness advantages including immune evasion, stress tolerance, and resistance to antibiotics and antibacterials. In this review, we summarize the current knowledge of major A. baumannii OMPs and discuss their versatile role in antibiotic resistance and virulence. Specifically, we explore how OmpA, CarO, and OprD-like porins mediate antibiotic and amino acid shuttle and host virulence.

Acinetobacter baumannii: An Ancient Commensal with Weapons of a Pathogen

“…Since recent papers provide detailed coverage of the genes and mechanisms used by A. baumannii to gain resistance to antibiotics, including carbapenems and colistin, this topic will not be discussed in detail and the reader is referred to [ 37 , 38 , 39 ]. To improve our knowledge of A. baumannii pathogenesis and develop new strategies to combat infections, several studies investigated its virulence factors [ 11 , 18 , 40 , 41 , 42 ]. Remarkably, A. baumannii has a huge pathogenic potential that enables it to firmly resist in the environment, form biofilms, move, interact with host cells, capture micronutrients, and secrete proteins [ 3 , 13 , 16 , 18 , 41 , 42 , 43 , 44 ].…”

“…Outer membrane proteins (Omps) embedded within the outer membrane (OM) are cornerstone proteins involved in cellular permeability and virulence in A. baumannii . These monomeric or trimeric β-barrel proteins, also known as porins, connect the external environment to the periplasmic space, allowing the diffusion of nutrients as well as small molecules, antibiotics, and disinfectants [ 18 , 40 , 41 , 44 , 51 ]. To date, identified Omps in A. baumannii are OmpA, CarO, OprD-like, Omp33-36 kDa, OmpW, AbuO, TolB, DcaP, Oma87/BamA, NmRmpM, CadF, OprF, LptD [ 18 , 41 , 44 ].…”

“…These monomeric or trimeric β-barrel proteins, also known as porins, connect the external environment to the periplasmic space, allowing the diffusion of nutrients as well as small molecules, antibiotics, and disinfectants [ 18 , 40 , 41 , 44 , 51 ]. To date, identified Omps in A. baumannii are OmpA, CarO, OprD-like, Omp33-36 kDa, OmpW, AbuO, TolB, DcaP, Oma87/BamA, NmRmpM, CadF, OprF, LptD [ 18 , 41 , 44 ]. Besides its role in antibiotic-resistance, OmpA plays a central role in A. baumannii virulence, including, serum resistance, biofilm formation, host-interaction, cytotoxicity, and apoptosis [ 11 , 18 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 122 ].…”

OmpA Protein-Deficient Acinetobacter baumannii Outer Membrane Vesicles Trigger Reduced Inflammatory Response

“…In this study we aimed to investigate the cytotoxic and immunomodulatory properties of OMVs secreted by clinical A. baumannii strain and its ompA gene deletion mutant. We demonstrated that OmpA protein could modulate the response of murine macrophages not only by being incorporated into the outer membrane of bacteria [ 19 ], but also as the component of OMVs, thereby expanding its effect in the infected host tissues.…”

Molecular characterization of lpxACD and pmrA/B two-component regulatory system in the colistin resistance Acinetobacter baumannii clinical isolates

“…Furthermore, resistance due to lipid A modifications by a mutation in PmrAB two-component regulatory system has a relatively low biologic cost, especially concerning A. baumannii virulence (Wand et al, 2015). Third mechanism of Col-R involve, activation of a broadspectrum efflux pump by mutation in the ΔemrB gene family or changes in membrane permeability through reduction in the number of entry channels, like ompA porin (Uppalapati et al, 2020;Lin et al, 2017). Recent research on mechanism of Col-R in A. baumannii suggest that, the disruption of the global regulator H-NS by insertion sequence ISAba125 into lpxA, lpxC and lpxD is playing an important role in the Col-R A. baumannii.…”