Abstract

Pathogenomic analysis was performed on a novel carbapenem-resistant Citrobacter freundii isolate (H2730R) from a rectal swab of an adult male patient admitted to a tertiary hospital, Durban, South Africa. H2730R was identified using selective media and API 20e kit. Confirmatory identification and antibiotic susceptibility testing were performed using the VITEK II. H2730R was whole-genome sequenced on the Illumina MiSeq platform. H2730R was resistant to all tested antibiotics except tigecycline and was defined as ST498 by the C. freundii multilocus sequence typing (MLST) database. The estimated pathogenic potential predicted a higher probability (Pscore ≈ 0.875), supporting H2730R as a human pathogen. H2730R harbored 25 putative acquired resistance genes, 4 plasmid replicons, 4 intact prophages, a class 1 integron (IntI1), 2 predominant insertion sequences (IS3 and IS5), numerous efflux genes, and virulome. BLASTn analysis of the blaNDM-1 encoding contig (00022) and its flanking sequences revealed the blaNDM-1 was located on a plasmid similar to the multireplicon p18-43_01 plasmid reported for the spread of carbapenem resistance in South Africa. Phylogenomic analysis showed clustering of H2730R with CF003/CF004 strains in the same clade, suggesting a possible association between C. freundii strains/clones. Acquiring the p18-43_01 plasmid containing blaNDM-1, the diversity, and complex resistome, virulome, and mobilome of this pathogen makes its incidence very worrying regarding mobilized resistance. This study presents the background genomic information for future surveillance and tracking of the spread of carbapenem-resistant Enterobacteriaceae in South Africa.

Highlights

  • Citrobacter freundii (C. freundii) is a rod-shaped, Gram-negative, aerobic member of the Enterobacterales family that is an intestinal commensal in humans and animals [1,2]

  • We present the emergence of a novel carbapenem-resistant sequence type (ST498) of C. freundii isolated from a rectal swab of an adult male patient admitted to a tertiary healthcare facility in Durban, South Africa, harboring a diverse resistome, virulome, and mobilome

  • We show the phylogenomic relationship between this novel isolate (H2730R) and all the deposited C. freundii genomes from South Africa at the Pathosystems Resource Integration Center (PATRIC) online platform

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Summary

Introduction

Citrobacter freundii (C. freundii) is a rod-shaped, Gram-negative, aerobic member of the Enterobacterales family that is an intestinal commensal in humans and animals [1,2]. It is a known cause of nosocomial infections associated with the biliary tract, respiratory tract, urinary system, and central nervous system, including meningitis, neonatal sepsis, and infectious diarrhea [3,4]. The emergence and dissemination of drug-resistant C. freundii in humans, animals, and the environment have previously been described, making this pathogen a potential reservoir for the spread of antimicrobial-resistant genes [1,2,4,5,6,7].

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