Microevolution in the major outer membrane protein OmpA of Acinetobacter baumannii

VIALE ALEJANDRO M; EVANS, BENJAMIN

Frankfurt

Simposio; 12th International Symposium on the Biology of Acinetobacter; 2019

OmpA is the most abundant protein in the outer membrane of Acinetobacter baumannii, and has beenproposed as a vaccine target. It forms an 8-stranded beta-barrel domain embedded in the outermembrane, four extra-cellular external loops (ELs), and a C-terminal periplasmic domain that binds tocell wall peptidoglycan. A. baumannii OmpA proposed functions range from a porin involved in antibioticresistance, host cell adhesion and invasion, and biofilm formation, representing many different, potentiallycompeting, selective pressures acting upon the protein. Here, we analysed the polymorphisms inAcinetobacter OmpA to obtain clues on how the clinical environment may have shaped the evolution ofthis protein.Analysis of nearly 250 Acinetobacter genomes identified five major groups of ompA alleles, named V1 toV5, comprising 50 different alleles coding for 29 different protein variants. Across the protein sequence,17% of amino acid positions were polymorphic, with polymorphisms concentrated in 5 regionscorresponding to the four ELs and the C-terminal end of the protein. Evidence for intra-genicrecombination was seen, for example between the V3 and V4 groups at EL1, the V2 and V4 groups atEL4, and a 6 amino-acid indel located at the C-terminal end of the protein. When mapped against a coregene phylogeny, ompA alleles were not randomly distributed, with the V1a1 allele almost exclusive toMLST clonal complex 1 (CC1) strains (Pasteur MLST typing scheme), while the V2a1 allele was found in26/31 CC2 strains. Evidence was found for exchange of ompA alleles between different A. baumanniilineages, and between different Acinetobacter species. Analyses of the substitution patterns of the alleleswithin V groups found little evidence for positive selection of the ELs, but suggested that non-synonymoussubstitutions in the transmembrane regions between species may have been selected.In conclusion, we find a diversity of OmpA alleles in A. baumannii, and that major global clones preservedtheir clone-associated allele, suggesting they confer significant fitness advantages. Lateral gene transferand recombination appear to drive the evolution of OmpA in this species, such as the acquisition of a Cterminalinsertion that may stabilise the bacterial envelope. These data demonstrate that any ompA allelethat evolves a clinically relevant phenotype can spread within and between Acinetobacter species, andthat a vaccine based upon OmpA may be limited in its effectiveness.