Genomic and Phenotypic Analyses of Acinetobacter baumannii Isolates From Three Tertiary Care Hospitals in Thailand.

Jessica Loraine,Potjanee Srimanote,Rosesathorn Soontarach,Pattarachai Kiratisin,Supayang P Voravuthikunchai,Peter W Taylor,Nicholas R Thomson,Grace A Blackwell,Eva Heinz,Richard A Stabler

doi:10.3389/fmicb.2020.00548

Abstract

Antibiotic resistant strains of Acinetobacter baumannii are responsible for a large and increasing burden of nosocomial infections in Thailand and other countries of Southeast Asia. New approaches to their control and treatment are urgently needed and an attractive strategy is to remove the bacterial polysaccharide capsule, and thus the protection from the host’s immune system. To examine phylogenetic relationships, distribution of capsule chemotypes, acquired antibiotic resistance determinants, susceptibility to complement and other traits associated with systemic infection, we sequenced 191 isolates from three tertiary referral hospitals in Thailand and used phenotypic assays to characterize key aspects of infectivity. Several distinct lineages were circulating in three hospitals and the majority belonged to global clonal group 2 (GC2). Very high levels of resistance to carbapenems and other front-line antibiotics were found, as were a number of widespread plasmid replicons. A high diversity of capsule genotypes was encountered, with only three of these (KL6, KL10, and KL47) showing more than 10% frequency. Almost 90% of GC2 isolates belonged to the most common capsule genotypes and were fully resistant to the bactericidal action of human serum complement, most likely protected by their polysaccharide capsule, which represents a key determinant of virulence for systemic infection. Our study further highlights the importance to develop therapeutic strategies to remove the polysaccharide capsule from extensively drug-resistant A. baumanii during the course of systemic infection.

Highlights

A. baumannii is an opportunistic pathogen that can cause potentially lethal nosocomial infections (Howard et al, 2012)
single-nucleotide polymorphisms (SNPs) were called against the A. baumannii reference genome to identify heterozygous SNPs, and isolates with more than 2% were removed from further analysis (Page et al, 2016a), resulting in the 191 genomes analyzed in this study
An additional challenge further narrowing the spectrum of available options for highly resistant A. baumannii infections is that last-line treatments available often overlap with other highly problematic infections

Summary

INTRODUCTION

A. baumannii is an opportunistic pathogen that can cause potentially lethal nosocomial infections (Howard et al, 2012) These are frequently a result of trauma, surgery, catheterization or endotracheal intubation (Chopra et al, 2014), and A. baumannii can escape the local immune reaction by evading neutrophils, macrophages and complement (C') (Russo et al, 2008; García-Patiño et al, 2017). This immune escape necessitates the use of antimicrobials, and the key determinant of clinical outcome of A. baumannii infection is treatment failure due to the high number of antibiotic resistant strains (Wong et al, 2017). We sought to identify factors that contribute to the capacity of GC2 isolates to cause infection through increased virulence (Zarrilli et al, 2013), using genomic data and bioassays, in relation to the role of the capsule in the determination of resistance to C'-mediated attack

MATERIALS AND METHODS

DISCUSSION

Findings

DATA AVAILABILITY STATEMENT