Genomic epidemiology and heterogeneity of <i>Providencia</i> and their <i>bla</i>_NDM-1-carrying plasmids

<i>Providencia</i> as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant <i>Providencia</i> strains poses a potentially life-threatening risk to public health. However, a comprehensive genomic study to reveal the population structure and dissemination of <i>Providencia</i> is still lacking. In this study, we conducted a genomic epidemiology analysis on the 580 global sequenced <i>Providencia</i> isolates, including 257 ones sequenced in this study (42 ones were fully sequenced). We established a genome sequence-based species classification scheme for <i>Providencia</i>, redefining the conventional 11 <i>Providencia</i> species into seven genocomplexes that were further divided into 18 genospecies, providing an extensively updated reference for <i>Providencia</i> species discrimination based on the largest <i>Providencia</i> genome dataset to date. We then dissected the profile of antimicrobial resistance genes and the prevalence of multi-drug-resistant <i>Providencia</i> strains among these genocomplexes/genospecies, disclosing the presence of diverse and abundant antimicrobial resistance genes and high resistance ratios against multiple classes of drugs in <i>Providencia</i>. We further dissected the genetic basis for the spread of <i>bla</i>_NDM-1 in <i>Providencia</i>. <i>bla</i>_NDM-1 genes were mainly carried by five incompatible (Inc) groups of plasmids: IncC, IncW, Inc_pPROV114-NR, Inc_pCHS4.1-3, and Inc_pPrY2001, and the last three were newly designated in this study. By tracking the spread of <i>bla</i>_NDM-1-carrying plasmids, IncC, Inc_pPROV114-NR, Inc_pCHS4.1-3, and Inc_pPrY2001 plasmids were found to be highly involved in parallel horizontal transfer or vertical clonal expansion of <i>bla</i>_NDM-1 among <i>Providencia</i>. Overall, our study provided a comprehensive genomic view of species differentiation, antimicrobial resistance prevalence, and plasmid-mediated <i>bla</i>_NDM-1 dissemination in <i>Providencia</i>.