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

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.