Genomic epidemiology and heterogeneity of Providencia and their bla _NDM-1-carrying plasmids

Providencia as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant Providencia strains poses a potentially life-threatening risk to public health. However, a comprehensive genomic study to reveal the population structure and dissemination of Providencia is still lacking. In this study, we conducted a genomic epidemiology analysis on the 580 global sequenced Providencia isolates, including 257 ones sequenced in this study (42 ones were fully sequenced). We established a genome sequence-based species classification scheme for Providencia, redefining the conventional 11 Providencia species into seven genocomplexes that were further divided into 18 genospecies, providing an extensively updated reference for Providencia species discrimination based on the largest Providencia genome dataset to date. We then dissected the profile of antimicrobial resistance genes and the prevalence of multi-drug-resistant Providencia 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 Providencia. We further dissected the genetic basis for the spread of bla(NDM-1) in Providencia. bla(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 bla(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 bla(NDM-1) among Providencia. Overall, our study provided a comprehensive genomic view of species differentiation, antimicrobial resistance prevalence, and plasmid-mediated bla(NDM-1) dissemination in Providencia.