Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a nosocomial pathogen that has emerged as a global threat because of high levels of resistance to many antibiotics, particularly those considered to be last-resort antibiotics, such as carbapenems. Although alterations in the efflux pump and outer membrane proteins can cause carbapenem resistance, the main mechanism is the acquisition of carbapenem-hydrolyzing oxacillinase-encoding genes. Of these, oxa23 is by far the most widespread in most countries, while oxa24 and oxa58 appear to be dominant in specific regions. Historically, much of the global spread of carbapenem resistance has been due to the dissemination of two major clones, known as global clones 1 and 2, although new lineages are now common in some parts of the world. The analysis of all publicly available genome sequences performed here indicates that ST2, ST1, ST79 and ST25 account for over 71 % of all genomes sequenced to date, with ST2 by far the most dominant type and oxa23 the most widespread carbapenem resistance determinant globally, regardless of clonal type. Whilst this highlights the global spread of ST1 and ST2, and the dominance of oxa23 in both clones, it could also be a result of preferential selection of carbapenem-resistant strains, which mainly belong to the two major clones. Furthermore, ~70 % of the sequenced strains have been isolated from five countries, namely the USA, PR China, Australia, Thailand and Pakistan, with only a limited number from other countries. These genomes are a vital resource, but it is currently difficult to draw an accurate global picture of this important superbug, highlighting the need for more comprehensive genome sequence data and genomic analysis.

Accumulation of Antibiotic Resistance Genes in Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Lineage 2, Global Clone 1, from Outbreaks in 2012–2013 at a Tehran Burns Hospital

“…This study showed that all Iranian outbreak strains belong to the same sequence type, ST328 in the Institut Pasteur scheme, and share many properties, such as resistance to the frontline carbapenem antibiotics, conferred by the carbapenem resistance oxa23 gene in Tn2006 within AbaR4, which is located in the chromosomal comM gene, and a plasmid that carries oxa24. This study further represents the first analysis of the genetic context of the most widespread carbapenem resistance gene, oxa23 (19), in A. baumannii isolates recovered from Iran. In A. baumannii strains that belong to the two major global clones, resistance genes often reside in the chromosome within large genomic islands (6, 23, 24).…”

“…CRAB was placed as the number 1 critical priority pathogen on the World Health Organization's list of 12 multiresistant bacteria for which immediate research on new therapeutics and antibiotic development is required (44). However, despite the global distribution of CRAB and the need to have data from all countries, there is a substantial gap in WGS data from most geographical regions across the globe, as the bulk of the current publicly available genome sequence data is from only 4 countries, namely, the United States, China, Thailand, and Australia (19). The lack of sequence data has made it difficult to track the spread of resistance at the global level and determine the population structure of this microorganism (19).…”

“…Recently, a systematic review examining the rate of CRAB estimated an overall ϳ80% rate of resistance to carbapenems across the country, with 73%, 21%, and 6.2% of carbapenem-resistant isolates containing the oxa23, oxa24, and oxa58 oxacillin carbapenemase genes, respectively (14). However, to date, none of the studies investigated the genetic context and/or genomic location of the oxa23 gene, which is the most widely encountered carbapenem resistance gene in the country (14) and globally (19).…”

Comparison of methods for the detection of in vitro synergy in multidrug-resistant gram-negative bacteria

“…This is an important limitation of our study. We evaluated A. baumannii belonging to international STs such as ST15 and ST297 [28,29] as well as S. marcescens carrying KPC-the most frequent carbapenemase described for this organism [1,2]. Thus, our findings can be useful internationally.…”

Bloodstream infections caused by ST2 Acinetobacter baumannii over 6 years in China: risk factors, antibiotic regimens and virulence

“…The population of MDR-AB is characteristic of clonal dissemination, as revealed by multi-locus sequence typing (MLST). Clonal complex (CC) 2 is by far the most widely disseminated A. baumannii population in more than 30 countries, including China [8], and ST2 is dominant in CC2 [9]. ST2 has been reported to be associated with antimicrobial resistance [10][11].…”