Emergence of multidrug resistant Enterobacter spp. in Nigeria: a genomic study

Extended-spectrum β-lactamases (ESBL) and AmpC β-lactamase-producing Enterobacter species are pathogens of public health concern. In this study, we investigated the resistome, virulome, and plasmidome of circulating Enterobacter hormaechei isolated from humans, animals, and ready-to-eat (RTE) food in Dutsin-Ma, northwest Nigeria.

Enterobacter species were isolated from human, and RTE food samples using MacConkey and CHROM agar. Species identification and antibiotics susceptibility testing (AST) were performed using Microscan autoSCAN-4 and MALDI-TOF MS, respectively. Whole-genome sequencing (WGS) and bioinformatics analysis were performed to validate the species identities. WGS also determined sequence types (STs), resistome, plasmidome, and virulome using PubMLST, ResFinder, PlasmidFinder, and Virulence Factors Database (VFDB) via ABRicate, respectively.

E. hormaechei subs. xiangfangensis was the dominant species isolated from humans (6/8, 75%) and animals (1/8, 12.5%), while E. hormaechei subs. oharae was exclusively found in RTE food (1/8, 12.5%). The most frequent sequence type (ST) was ST813, found solely in humans, along with ST511, ST454, and the emerging high-risk ST171. ST68 was identified in food, and novel ST (ST3186) were identified in animal and human samples, respectively. All isolates exhibited 100% resistance to ampicillin and amoxicillin-clavulanic acid, with 62.5% resistant to each of aztreonam, ceftazidime, ciprofloxacin, gentamicin, tobramycin and cefotaxime, and 25% to colistin. E. hormaechei (62.5%) isolates carried the blaCTX-M-15 gene, encoding ESBL-production, along with AmpC genes such as blaCMH-3, and also harbored resistance genes for aminoglycosides, fluoroquinolones, sulfonamides, tetracyclines, and trimethoprim. The IncHI2 (50%) was identified as the dominant plasmid type followed by Col (pHAD28) (25%), IncFIB (25%), and IncFII (11.1%). The most (62.5%) prevalence virulence gene among the isolates is ompA encoding adhesion while each of entA, entB and fepD encoding iron acquisition were least (12.5%) occurred.

This study provides the first genomic insight into Enterobacter species in northwest Nigeria, highlighting their role in the spread of antimicrobial resistance. E. hormaechei subsp. xiangfangensis was identified as the main reservoir of ESBL and AmpC β-lactamases in this study. The discovery of novel STs with diverse virulence factors and plasmid replicon indicates potential horizontal gene transfer across different ecological niches. Our findings underscore the need for robust surveillance and control measures to combat the spread of MDR Enterobacter species across human, animal, and food niches.