Abstract
The emergence of extended-spectrum β-lactamase (ESBL)-producing multidrug resistant Klebsiella pneumoniae causing community urinary tract infections (CA-UTI) in healthy women undermines effective treatment and poses a public health concern. We performed a comprehensive genomic analysis (Illumina and MinION) and virulence studies using Caenorhabditis elegans nematodes to evaluate KpnU95, a blaCTX-M-15-producing CA-UTI K. pneumoniae strain. Whole genome sequencing identified KpnU95 as sequence type 1412 and revealed the chromosomal and plasmid-encoding resistome, virulome and persistence features. KpnU95 possess a wide virulome and caused complete C. elegans killing. The strain harbored a single novel 180.3Kb IncFIB(K) plasmid (pKpnU95), which encodes ten antibiotic resistance genes, including blaCTX-M-15 and qnrS1 alongside a wide persistome encoding heavy metal and UV resistance. Plasmid curing and reconstitution were used for loss and gain studies to evaluate its role on bacterial resistance, fitness and virulence. Plasmid curing abolished the ESBL phenotype, decreased ciprofloxacin MIC and improved bacterial fitness in artificial urine accompanied with enhanced copper tolerance, without affecting bacterial virulence. Meta-analysis supported the uniqueness of pKpnU95 and revealed plasmid-ST1412 lineage adaptation. Overall, our findings provide translational data on a CA-UTI K. pneumoniae ST1412 strain and demonstrates that ESBL-encoding plasmids play key roles in multidrug resistance and in bacterial fitness and persistence.
Highlights
Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae is a worldwide opportunistic bacteria belonging to the ESKAPE group [1]
We describe the virulome and the resistome of the K. pneumoniae strain U95 (KpnU95) strain and the complete sequence of a novel megaplasmid that encodes a wide resistome and multiple metal and UV resistance genes, which may contribute to the bacterial environmental persistence
We describe a meta-analysis with a collection of available K. pneumoniae sequence type 1412 (ST1412) genomes and demonstrate the co-existence of this clonal lineage with the multidrug resistance (MDR) megaplasmid
Summary
Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae is a worldwide opportunistic bacteria belonging to the ESKAPE group [1]. This pathogen poses a huge burden in human medicine due to its multidrug resistance (MDR) phenotype leading to limited treatment options [2]. K. pneumoniae is considered as the second most common uropathogen after Escherichia coli [6]. The emergence of this species in the community setting is disturbing due to its high antibiotic-resistant nature compared to E. coli, mainly due to the production of ESBLs [5,7]. There is limited knowledge on the genomics and the pathogenesis of community strains [9]
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