An insight into the genome of extensively drug-resistant and uropathogenic Citrobacter werkmanii

Abstract

ObjectiveCarbapenemase-producing bacteria pose a serious public-health threat. This study was performed to understand the emergence and genetic features of NDM-producers in hospital setting. MethodsSamples were collected from a tertiary-care hospital. Isolate identification was performed by 16S rRNA sequencing. The genome of Citrobacter werkmanii (AK-8) was sequenced on an Illumina NextSeq 500 platform. Resistance determinants and pathogenicity islands were determined by ResFinder and PathogenFinder, respectively. MLST, two-component systems and transcription factors were identified by P2RP server, whilst variant calling and insertion sequence (IS) elements were determined by Galaxy and ISfinder, respectively. The genome of AK-8 was compared with uropathogenic Escherichia coli strain 536. ResultsThis is the first report on whole-genome analysis of extensively drug-resistant NDM-6-producing uropathogenic C. werkmanii ST-104. Resistance genes for all antibiotics except colistin, fosfomycin, fusidic- acid, nitroimidazole, oxazolidinones, tetracycline and glycopeptides were detected in this strain. Genome analysis of AK-8 led to the identification of the BaeSR two-component system regulating production of multidrug efflux proteins. Virulence was regulated by CpxRA, ZraRS, RstAB, UhpAB, AcrAB, RcsBc and UvrY, whereas Bar–UvrY was found to control carbon metabolism, flagellum biosynthesis and biofilm formation. The AK-8 genome encodes 21 chemoreceptors involved in colonisation and pathogenesis. Fur family transcriptional regulator, cAMP receptor protein and RpoS were found to increase the virulence of AK-8. ntBLAST analysis showed 69.60% genetic identity with E. coli 536 as an adaptive feature for survival. ConclusionThe emergence of extensively drug-resistant pathogenic C. werkmanii is alarming and it should not be ignored as commensal.