title: Five decades of genome evolution in the globally distributed, extensively antibiotic-resistantAcinetobacter baumanniiglobal clone 1.
abstract: The majority ofAcinetobacter baumanniiisolates that are multiply, extensively and pan-antibiotic resistant belong to two globally disseminated clones, GC1 and GC2, that were first noticed in the 1970s. Here, we investigated microevolution and phylodynamics within GC1 via analysis of 45 whole-genome sequences, including 23 sequenced for this study. The most recent common ancestor of GC1 arose around 1960 and later diverged into two phylogenetically distinct lineages. In the 1970s, the main lineage acquired the AbaR resistance island, conferring resistance to older antibiotics, via a horizontal gene transfer event. We estimate a mutation rate of ∼5 SNPs genome- 1year- 1and detected extensive recombination within GC1 genomes, introducing nucleotide diversity into the population at >20 times the substitution rate (the ratio of SNPs introduced by recombination compared with mutation was 22). The recombination events were non-randomly distributed in the genome and created significant diversity within loci encoding outer surface molecules (including the capsular polysaccharide, the outer core lipooligosaccharide and the outer membrane protein CarO), and spread antimicrobial resistance-conferring mutations affecting thegyrAandparCgenes and insertion sequence insertions activating theampCgene. Both GC1 lineages accumulated resistance to newer antibiotics through various genetic mechanisms, including the acquisition of plasmids and transposons or mutations in chromosomal genes. Our data show that GC1 has diversified into multiple successful extensively antibiotic-resistant subclones that differ in their surface structures. This has important implications for all avenues of control, including epidemiological tracking, antimicrobial therapy and vaccination.
authors.affiliation: 1​ Department of Biochemistry & Molecular Biology, The University of Melbourne, Royal Parade, Parkville, Victoria, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Holt
authors.affiliation: 2​ School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Johanna J
authors.initials: JJ
authors.lastname: Kenyon
authors.affiliation: 3​ School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hamidian
authors.affiliation: 4​ Centre for Systems Genomics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Schultz
authors.affiliation: 5​ Wellcome Sanger Trust Institute, Hinxton, Cambridge, UK.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Pickard
authors.affiliation: 5​ Wellcome Sanger Trust Institute, Hinxton, Cambridge, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: 3​ School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hall
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D016680:Genome, Bacterial / Q000235:genetics*; D010957:Plasmids / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements
keywords: Acinetobacter baumannii; antibiotic resistance; capsule; evolution; phylogenomics; recombination