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Background   Salmonella enterica subsp. enterica  serovar Napoli ( S . Napoli) is among the top serovars causing human infections in Italy, although it is relatively uncommon in other European countries; it is mainly isolated from humans and the environment, but neither the reservoir nor its route of infection are clearly defined. This serovar is characterized by high genomic diversity, and molecular evidences revealed important similarities with typhoidal serovars.    Results  179  S . Napoli genomes as well as 239 genomes of typhoidal and non-typhoidal serovars were analyzed in a comparative genomic study. Phylogenetic analysis and draft genome characterization in terms of Multi Locus Sequence Typing (MLST), plasmid replicons,  Salmonella  Pathogenicity Islands (SPIs), antimicrobial resistance genes (ARGs), phages, biocide and metal-tolerance genes confirm the high genetic variability of  S . Napoli, also revealing a within-serovar phylogenetic structure more complex than previously known. Our work also confirms genomic similarity of  S . Napoli to typhoidal serovars ( S . Typhi and  S . Paratyphi A), with  S . Napoli samples clustering primarily according to ST, each being characterized by specific genomic traits. Moreover, two major subclades of  S . Napoli can be clearly identified, with ST-474 being biphyletic. All STs span among isolation sources and years of isolation, highlighting the challenge this serovar poses to define its epidemiology and evolution. Altogether,  S . Napoli strains carry less SPIs and less ARGs than other non-typhoidal serovars and seldom acquire plasmids. However, we here report the second case of an extended-spectrum β–lactamases (ESBLs) producing  S . Napoli strain and the first cases of multidrug resistant (MDR)  S . Napoli strains, all isolated from humans.    Conclusions  Our results provide evidence of genomic plasticity of  S.  Napoli, highlighting genomic similarity with typhoidal serovars and genomic features typical of non-typhoidal serovars, supporting the possibility of survival in different niches, both enteric and non-enteric. Presence of horizontally acquired ARGs and MDR profiles rises concerns regarding possible selective pressure exerted by human environment on this pathogen.

Comparative genomic analysis reveals high intra-serovar plasticity within Salmonella Napoli isolated in 2005–2017