Origin, Phylogeny, and Transmission of the Epidemic Clone ST208 of Carbapenem-Resistant Acinetobacter baumannii on a Global Scale

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic pathogen that has become a global threat. The dissemination of global clone 2 (GC2) CRAB has been well documented. Oxford sequence type (ST) 208 is one of the most prevalent lineages of A. baumannii GC2; however, its evolution and phylogeny are unclear. We collected 45 representative ST208 isolates from 14 cities in China between 1999 and 2018. Moreover, 411 ST208 genome sequences were downloaded from the GenBank database for comparison. The global ST208 phylogeny showed that ST208 might have originated from North America and subsequently evolved into two clades. Notably, the widespread OXA-23-producing ST208 A. baumannii was correlated with the transposon structure and dynamics of replicative transposition, and the Tn2009 tandem structure of five copies of bla(OXA-23) and potential circular intermediate of Tn2009 were first detected. Furthermore, 15 Chinese ST208 isolates carried GR25 pABTJ1-like plasmids, which contained bla(OXA-23) and have only been found in China in the last decade. In conclusion, our work suggests that replicative transposition contributes to the evolution and transmission of OXA-23-producing ST208 A. baumannii and highlights the new challenges posed by the epidemiological surveillance of globally distributed clonal groups via whole genome sequencing. IMPORTANCE ST208 as one of the most prevalent lineages of CRAB has caused several difficult-to-treat infections and outbreaks around the world. However, few studies have focused on evaluating the genetic background differences of ST208 A. baumannii isolated from very distant geographic regions. A comprehensive genomic analysis of 456 clinical strains of ST208 A. baumannii from a wide temporal and geographic range was performed in this study. Moreover, the mechanisms leading to the horizontal transfer of bla(OXA-23) in ST208 A. baumannii are poorly understood. We first describe experimental evidence of the potential circular intermediate of Tn2009, and the Tn2009 tandem structure of five copies of bla(OXA-23) was first detected. The interbacterial transfer of genetic elements carrying resistance to last-line antibiotic carbapenems highlights the essential need to enhance epidemiologic surveillance.