Characterising Australian Elizabethkingia clinical isolates using comparative genomics and antimicrobial resistance

The Elizabethkingia genus has gained global attention in recent years as a nosocomial pathogen. Elizabethkingia spp. are intrinsically multidrug resistant, primarily infect immunocompromised individuals, and are associated with high mortality (~20-40%). Although Elizabethkingia infections appear sporadically worldwide, gaps remain in our understanding of global strain relatedness and patterns of antimicrobial resistance. To address these knowledge gaps, 22 Elizabethkingia spp. clinical isolates collected in Queensland, Australia, over a 16-year period were examined using MALDI-TOF MS (Vitek MS) and whole-genome sequencing (WGS) and compared with a global strain dataset. Phylogenomic reconstruction against all publicly available strains (n=100) robustly identified 16 E. anophelis, three E. miricola, two E. meningoseptica and one E. bruuniana, most with previously undescribed diversity. Global relationships suggest Australian E. anophelis isolates may have ancient origins from the USA, England and Asia, in addition to more recent transmission events. Genomic examination of closely related strains identified evidence of nosocomial transmission in patients admitted several months? apart, suggesting infection via an unidentified, shared hospital environmental source. Furthermore, broth microdilution of the 22 Elizabethkingia isolates against 39 antibiotics revealed almost ubiquitous resistance to aminoglycosides, carbapenems, cephalosporins and penicillins, with susceptibility to fluoroquinolones and tetracyclines. Our results demonstrate that Australian Elizabethkingia are genetically diverse, with some strains closely related to previously reported strains from other continents. Further, we confirm that antimicrobial therapy options for Elizabethkingia infections are limited due to intrinsic drug resistance; however, Australian isolates appear susceptible to minocycline, levofloxacin and trimethoprim/sulfamethoxazole, suggesting that these antimicrobials may provide effective therapy for Elizabethkingia infections. Elizabethkingia spp. are a genus of Gram-negative, multidrug resistant, environmental pathogens. As an uncommon cause of nosocomial and community-acquired infections, Elizabethkingia are known to infect those with underlying co-morbidities and/or immunosuppression, which in conjunction with incorrect empirical antimicrobial therapy can contribute to transmission of infection and high mortality (~20-40%). Elizabethkingia have an underlying presence in Australian hospitals and patients; however, the origin, epidemiology, and antibiotic resistance of these strains is yet to be understood. Here, we performed phylogenomic analyses of clinical Australian Elizabethkingia spp., to understand global relationships and minimum inhibitory concentration testing to gather antimicrobial resistance profiles. Our findings identified a highly diverse Elizabethkingia population in Australia, with many being genetically related to international strains and near consistent susceptibility to tetracyclines, fluoroquinolones and trimethoprim/sulfamethoxazole. We provide new insights into the origins and epidemiology of Elizabethkingia spp., in addition to their multidrug resistance and treatment options, which has implications to managing infections and detecting outbreaks globally.