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

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.

Predominance of international clone 2 multidrug-resistant Acinetobacter baumannii clinical isolates in Thailand: a nationwide study

“…Although CC1 and CC2 have been identified as the key clonal lineages globally, no isolates belonging to CC1 were detected in this study. CC2 was by far the most abundant A. baumannii clone, with a broad international distribution over many continents [ 26 , 47 – 50 ]. CC2 in the Pasteur scheme corresponds to CC92 in the Oxford scheme and international clone II, as previously identified [ 42 ].…”

OmpA Protein-Deficient Acinetobacter baumannii Outer Membrane Vesicles Trigger Reduced Inflammatory Response

“…By changing the composition of OMVs, bacteria could manipulate host immune system [ 41 , 42 ]. Therefore, a detailed examination of OMVs composition is needed considering the high diversity of virulence-related features of clinical A. baumannii strains [ 20 , 43 ].…”

Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses

“…g Strains were determined to be resistant to multiple classes of antibiotics that include a fluoroquinolone (n = 1), aminoglycosides (n = 2), a tetracycline (n = 1) and b-lactam antibiotics including carbapenems (n = 9). All three strains were sensitive to colistin (37).…”

“…Nine A. baumannii strains were isolated in 2016 from clinical specimens obtained from two tertiary hospitals in Thailand, Siriraj Hospital, Bangkok and Songklanagarind Hospital, Songklanagarind Hospital, Hat Yai, Songkhla Province. These strains subsequently underwent whole-genome sequencing and sequence typing (37). The nine isolates tested had a range of multilocus sequence typing (MLST) sequence types (ST) and KL types including five ST2 (representing global clone 2), three ST215 and one ST164 strains and three KL47, two KL10, two KL52, one KL6 and one KL2 capsular loci strains (Table 1).…”

“…Although anti-capsular antibody protects against A. baumannii infections in both mice (34) and rat (35) infection models, over 100 unique capsule loci (KL types) have been described for A. baumannii clinical strains (36). For example, a recent evaluation of 191 isolates collected from three tertiary hospitals in Thailand reported high capsule type diversity with a total of 24 KL types identified, and the three KL types with the highest prevalence KL10, KL6 and KL47 only accounting for 15.7%, 15.2% and 11.0% of the isolates evaluated respectively (37). This diversity inhibits using A. baumannii capsular antigen as the target for a monoclonal antibody therapy.…”