Search

ABSTRACT We recently reported the recovery of a conjugative virulence plasmid, p15WZ-82_Vir, from a clinical Klebsiella variicola strain. In this study, we found that several new plasmid types were generated due to genetic rearrangement. Partial integration of plasmid p15WZ-82_Vir with existing plasmids such as resistance plasmids by different homologous recombination events was observable in three recipient strains. Such recombination events enable the formation of various types of mosaic plasmids simultaneously carrying virulence-encoding and antibiotic resistance-encoding genes as well as genes involved in plasmid conjugation, which promote transmission of various virulence-encoding and resistance-encoding elements among pathogens. Our data also suggest that these conjugative events may play an integral role in the development of novel mosaic plasmids, which is vital for plasmid evolution. IMPORTANCE Although they are often nonconjugative, large virulence plasmids are increasingly detected in clinical K. pneumoniae and contribute to the hypervirulence phenotype of this organism. In this study, we demonstrated that the virulence-encoding region that originated from virulence plasmid pLVPK actively interacted with different types of plasmids via homologous recombination to generate new conjugative plasmids. This report provides insights into the evolution of self-transmissible plasmids carrying genetic elements encoding both hypervirulent and multidrug-resistant phenotypes, which facilitate the rapid development of clinical K. pneumoniae strains that are hypervirulent and multidrug resistant.

ABSTRACT Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009–2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.