The Widespread Multidrug-Resistant Serotype O12 Pseudomonas aeruginosa Clone Emerged through Concomitant Horizontal Transfer of Serotype Antigen and Antibiotic Resistance Gene Clusters

Abstract

The O-specific antigen (OSA) in Pseudomonas aeruginosa lipopolysaccharide is highly varied by sugar identity, side chains, and bond between O-repeats. These differences classified P. aeruginosa into 20 distinct serotypes. In the past few decades, O12 has emerged as the predominant serotype in clinical settings and outbreaks. These serotype O12 isolates exhibit high levels of resistance to various classes of antibiotics. Here, we explore how the P. aeruginosa OSA biosynthesis gene clusters evolve in the population by investigating the association between the phylogenetic relationships among 83 P. aeruginosa strains and their serotypes. While most serotypes were closely linked to the core genome phylogeny, we observed horizontal exchange of OSA biosynthesis genes among phylogenetically distinct P. aeruginosa strains. Specifically, we identified a “serotype island” ranging from 62 kb to 185 kb containing the P. aeruginosa O12 OSA gene cluster, an antibiotic resistance determinant (gyrAC248T), and other genes that have been transferred between P. aeruginosa strains with distinct core genome architectures. We showed that these genes were likely acquired from an O12 serotype strain that is closely related to P. aeruginosa PA7. Acquisition and recombination of the “serotype island” resulted in displacement of the native OSA gene cluster and expression of the O12 serotype in the recipients. Serotype switching by recombination has apparently occurred multiple times involving bacteria of various genomic backgrounds. In conclusion, serotype switching in combination with acquisition of an antibiotic resistance determinant most likely contributed to the dissemination of the O12 serotype in clinical settings.

Application of Whole-Genome Sequencing Data for O-Specific Antigen Analysis and In Silico Serotyping of Pseudomonas aeruginosa Isolates

“…1). Compared to other studies (11,14,17), PAst optimizes in silico serotyping further by distinguishing members of the O2 serogroup through identification of the acquired phagerelated wzy ␤ within serotypes O2 and O16 (21,22). This enables typing into 12 serogroups as opposed to the 11 described by Raymond et al (16).…”

“…The database was constructed using the WGS data of the 20 P. aeruginosa IATS serotype reference isolates (14). The genomes were assembled using SPAdes (19), and the OSA clusters were extracted via identification of the ihfB/himD gene flanking the cluster upstream and the wbpM gene flanking the cluster downstream.…”

“…This implies that these particular LPS structures improve fitness within the hosts and the hospital environments in ways that we currently do not understand. Specifically for the O12 serotype, it has been shown that horizontal gene transfer of LPS genes has resulted in MDR isolates and the switching of a certain serotype to O12 (14). To continuously monitor LPS structure and evolution, serotyping can help to improve our understanding of the isolates that successfully in-fect patients.…”

“…The 20 serotypes harbor 11 distinct OSA gene clusters, each with a high number of unique genes (16). With the emergence of whole-genome sequencing (WGS) methods, it is now possible to assign an isolate to one of 11 serogroups based on the sequence and structure of the OSA gene cluster (11,14,17).…”

Antibiotic susceptibility and serotype patterns of Pseudomonas aeruginosa from clinical isolates in Abidjan, Cote dIvoire

“…The emergence of multidrug-resistant strains of P. aeruginosa in hospital is often associated with some serotypes (Thrane et al, 2015). In order to find an epidemiological link between the strains of P. aeruginosa isolated in hospital, phenotypic markers such as antibiotype and serotype are used to differentiate strains before genetic characterization (Blot et al, 2013;Wolska et al, 2012).…”