Comparative Genome Sequence Analysis of Multidrug-Resistant Acinetobacter baumannii

Abstract

The recent emergence of multidrug resistance (MDR) in Acinetobacter baumannii has raised concern in health care settings worldwide. In order to understand the repertoire of resistance determinants and their organization and origins, we compared the genome sequences of three MDR and three drug-susceptible A. baumannii isolates. The entire MDR phenotype can be explained by the acquisition of discrete resistance determinants distributed throughout the genome. A comparison of closely related MDR and drug-susceptible isolates suggests that drug efflux may be a less significant contributor to resistance to certain classes of antibiotics than inactivation enzymes are. A resistance island with a variable composition of resistance determinants interspersed with transposons, integrons, and other mobile genetic elements is a significant but not universal contributor to the MDR phenotype. Four hundred seventy-five genes are shared among all six clinical isolates but absent from the related environmental species Acinetobacter baylyi ADP1. These genes are enriched for transcription factors and transporters and suggest physiological features of A. baumannii that are related to adaptation for growth in association with humans.Among gram-negative pathogens that are reported as "multidrug resistant" (MDR), Acinetobacter baumannii is rapidly becoming a focus of significant attention (1,10,35,56). A. baumannii, a pleomorphic, gram-negative coccobacillus, is currently recognized by the Infectious Diseases Society of America as one of the most important pathogens threatening our health care delivery system (48). Global surveillance programs conducted over the last decade show an unparalleled increase in resistance rates among clinical Acinetobacter isolates (26). Acinetobacter spp. are now the third leading cause of respiratory tract infections among patients in intensive care units, and A. baumannii is responsible for up to 10% of hospital-acquired infections (26). These nosocomial infections are typically found in immunocompromised patients and are associated with an increased length of stay and excess morbidity (13,25,38,47 (19,40). Molecular typing of isolates from this outbreak revealed eight major clone types, and about 60% of the isolates were related to three pan-European types (5, 52), suggesting multiple independent origins (40). Examination of specific resistance determinants in the WRAMC isolates demonstrated considerable variability in the composition of resistance genes within each clone type and similar patterns across certain divergent clone types. Thus, genetic relatedness was a poor predictor of the MDR phenotype. This led to the hypothesis that there exist multiple independent genetic mechanisms leading to MDR in A. baumannii. A large cluster of antibiotic resistance genes and mobile genetic elements is present as an 86-kb "resistance island" (RI) in the A. baumannii AYE genome (15). The RI is not present in the genomes of the drug-susceptible A. baumannii isolates ATCC 17978 (43) and SDF (51), suggesting that it i...

Diverse responses to UV light exposure in Acinetobacter include the capacity for DNA damage-induced mutagenesis in the opportunistic pathogens Acinetobacter baumannii and Acinetobacter ursingii

“…CP000521; Smith et al, 2007). (Barbe et al, 2004), 'Acinetobacter oleivorans' DR1 (Jung et al, 2010), A. baumannii AB0057, AB900 and AB307-0294 (Adams et al, 2008), ACICU (Iacono et al, 2008), 17978 (Smith et al, 2007), and SDF and AYE (Vallenet et al, 2008). Table 1 provides specific strain descriptions.…”

Insights into Acinetobacter baumannii pathogenicity

“…medical devices and environmental surfaces (3)(4)(5)(6); (ii) its ability to adhere to, colonize and invade human epithelial cells (7,8); (iii) its repertoire of antibiotic resistance mechanisms that are able to be promptly up-regulated as required; and (iv) its ability to acquire foreign genetic material through lateral gene transfer to promote its own survival under antibiotic and host selection pressures (9,10). Specific virulence mechanisms identified to date are summarized in Table 1.…”

Are we closing in on an "elusive enemy"? The current status of our battle withAcinetobacter baumannii

“…In addition to many genes encoding resistance determinants, A. baumannii isolates possess "resistance islands (RIs)" and an "accessory genome." 13 A first example of the RI is the 86 kb RI described by Fournier et al 15 Since then ten RIs, also called "AbaRs," are also described and their significance in the evolution of resistance is being defined.…”

“…Whole genome sequence analysis of A. baumannii has shed light upon several fundamental features of this MDR and versatile pathogen. 13 Regarding the MDR phenotype, A. baumannii enjoys a variable complement of mobile genetic elements encoding drug-inactivating enzymes and insertion sequences (IS elements), develops a "plastic" genome, 14 and thus becomes resistant to many antimicrobials. In addition to many genes encoding resistance determinants, A. baumannii isolates possess "resistance islands (RIs)" and an "accessory genome."…”