title: Comparative genomics of multidrug resistance in Acinetobacter baumannii.
abstract: Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria commonly found in water and soil. This organism was susceptible to most antibiotics in the 1970s. It has now become a major cause of hospital-acquired infections worldwide due to its remarkable propensity to rapidly acquire resistance determinants to a wide range of antibacterial agents. Here we use a comparative genomic approach to identify the complete repertoire of resistance genes exhibited by the multidrug-resistant A. baumannii strain AYE, which is epidemic in France, as well as to investigate the mechanisms of their acquisition by comparison with the fully susceptible A. baumannii strain SDF, which is associated with human body lice. The assembly of the whole shotgun genome sequences of the strains AYE and SDF gave an estimated size of 3.9 and 3.2 Mb, respectively. A. baumannii strain AYE exhibits an 86-kb genomic region termed a resistance island--the largest identified to date--in which 45 resistance genes are clustered. At the homologous location, the SDF strain exhibits a 20 kb-genomic island flanked by transposases but devoid of resistance markers. Such a switching genomic structure might be a hotspot that could explain the rapid acquisition of resistance markers under antimicrobial pressure. Sequence similarity and phylogenetic analyses confirm that most of the resistance genes found in the A. baumannii strain AYE have been recently acquired from bacteria of the genera Pseudomonas, Salmonella, or Escherichia. This study also resulted in the discovery of 19 new putative resistance genes. Whole-genome sequencing appears to be a fast and efficient approach to the exhaustive identification of resistance genes in epidemic infectious agents of clinical significance.
authors.affiliation: Information Génomique et Structurale, Institute for Structural Biology and Microbiology, IBSM, Marseille, France. Pierre-Edouard.Fournier@univmed.fr
authors.forename: Pierre-Edouard
authors.initials: PE
authors.lastname: Fournier
authors.forename: David
authors.initials: D
authors.lastname: Vallenet
authors.forename: Valérie
authors.initials: V
authors.lastname: Barbe
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audic
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ogata
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirel
authors.forename: Hervé
authors.initials: H
authors.lastname: Richet
authors.forename: Catherine
authors.initials: C
authors.lastname: Robert
authors.forename: Sophie
authors.initials: S
authors.lastname: Mangenot
authors.forename: Chantal
authors.initials: C
authors.lastname: Abergel
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
authors.forename: Jean
authors.initials: J
authors.lastname: Weissenbach
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Claverie
mesh_terms: D000151:Acinetobacter Infections / Q000235:genetics; D040981:Acinetobacter baumannii / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D024901:Drug Resistance, Multiple, Bacterial; D005798:Genes, Bacterial; D005821:Genetic Techniques; D023281:Genomics; D006801:Humans; D008957:Models, Genetic; D016366:Open Reading Frames; D010802:Phylogeny