New Variant of Multidrug-Resistant <i>Salmonella enterica</i> Serovar Typhimurium Associated with Invasive Disease in Immunocompromised Patients in Vietnam

Abstract

Nontyphoidal <i>Salmonella</i> (NTS), particularly <i>Salmonella enterica</i> serovar Typhimurium, is among the leading etiologic agents of bacterial enterocolitis globally and a well-characterized cause of invasive disease (iNTS) in sub-Saharan Africa. In contrast, <i>S</i> Typhimurium is poorly defined in Southeast Asia, a known hot spot for zoonotic disease with a recently described burden of iNTS disease. Here, we aimed to add insight into the epidemiology and potential impact of zoonotic transfer and antimicrobial resistance (AMR) in <i>S</i> Typhimurium associated with iNTS and enterocolitis in Vietnam. We performed whole-genome sequencing and phylogenetic reconstruction on 85 human (enterocolitis, carriage, and iNTS) and 113 animal <i>S</i> Typhimurium isolates isolated in Vietnam. We found limited evidence for the zoonotic transmission of <i>S</i> Typhimurium. However, we describe a chain of events where a pandemic monophasic variant of <i>S</i> Typhimurium (serovar I:4,[5],12:i:- sequence type 34 [ST34]) has been introduced into Vietnam, reacquired a phase 2 flagellum, and acquired an IncHI2 multidrug-resistant plasmid. Notably, these novel biphasic ST34 <i>S</i> Typhimurium variants were significantly associated with iNTS in Vietnamese HIV-infected patients. Our study represents the first characterization of novel iNTS organisms isolated outside sub-Saharan Africa and outlines a new pathway for the emergence of alternative <i>Salmonella</i> variants into susceptible human populations.<b>IMPORTANCE</b><i>Salmonella</i> Typhimurium is a major diarrheal pathogen and associated with invasive nontyphoid <i>Salmonella</i> (iNTS) disease in vulnerable populations. We present the first characterization of iNTS organisms in Southeast Asia and describe a different evolutionary trajectory from that of organisms causing iNTS in sub-Saharan Africa. In Vietnam, the globally distributed monophasic variant of <i>Salmonella</i> Typhimurium, the serovar I:4,[5],12:i:- ST34 clone, has reacquired a phase 2 flagellum and gained a multidrug-resistant plasmid to become associated with iNTS disease in HIV-infected patients. We document distinct communities of <i>S</i> Typhimurium and I:4,[5],12:i:- in animals and humans in Vietnam, despite the greater mixing of these host populations here. These data highlight the importance of whole-genome sequencing surveillance in a One Health context in understanding the evolution and spread of resistant bacterial infections.