Microevolution in the major outer membrane protein OmpA of Acinetobacter baumannii

Acinetobacter baumannii is nowadays a relevant nosocomial pathogen characterized by multidrug resistance (MDR) and concomitant difficulties to treat infections. OmpA is the most abundant A. baumannii outer membrane (OM) protein, and is involved in virulence, host-cell recognition, biofilm formation, regulation of OM stability, permeability and antibiotic resistance. OmpA members are two-domain proteins with an N-terminal eight-stranded beta-barrel domain with four external loops (ELs) interacting with the environment, and a C-terminal periplasmic domain binding non-covalently to the peptidoglycan. Here, we combined data from genome sequencing, phylogenetic and multilocus sequence analyses from 975 strains/isolates of the Acinetobacter calcoaceticus/Acinetobacter baumannii complex (ACB), 946 from A. baumannii, to explore ompA microevolutionary divergence. Five major ompA variant groups were identified (V1 to V5) in A. baumannii, encompassing 52 different alleles coding for 23 different proteins. Polymorphisms were concentrated in five regions corresponding to the four ELs and the C-terminal end, and provided evidence for intra-genic recombination. ompA variants were not randomly distributed across the A. baumannii phylogeny, with the most frequent V1(lct)a1 allele found in most clonal complex 2 (CC2) strains and the second most frequent V2(lct)a1 allele in the majority of CC1 strains. Evidence was found for assortative exchanges of ompA alleles not only between separate A. baumannii lineages, but also different ACB species. The overall results have implications for A. baumannii evolution, epidemiology, virulence and vaccine design.