Whole Genome Sequencing RevealsEnterobacter hormaecheias a Key Bloodstream Pathogen in Six Tertiary Care Hospitals in Southwestern Nigeria
Authors: Oni Faith I. , Afolayan Ayorinde O. , Oaikhena Anderson O. , Odih Erkison Ewomazino , Ikhimiukor Odion O. , Ogunleye Veronica O. , Aboderin Aaron O. , Olabisi Olatunde F. , Amupitan Adewale A. , Fadeyi Abayomi , Raheem Rasaki A. , Olanipekun Bashirat A. , Elikwu Charles J. , Sadare Oluwadamilola A. , Oshun Phillip O. , Oduyebo Oyinlola O. , Ojo Folashade , Adeyemo Abolaji T. , Mba Ifeanyi E , Egwuenu Abiodun , Okwor Tochi , Underwood Anthony , Argimón Silvia , Ihekweazu Chikwe , Aanensen David M. , Okeke Iruka N. 
Published: December 2024

ABSTRACTEnterobacterspp. are an important cause of healthcare-associated bloodstream infections uncommonly reported in Africa. This study used whole genome sequencing (WGS) to characteriseEnterobacterspp. from hospitals in Nigeria’s antimicrobial resistance (AMR) surveillance system. Blood-culture isolates ofEnterobacterfrom six such tertiary-care hospitals recovered between 2014 and 2020 were re-identified and antimicrobial susceptibility-tested using VITEK2. Illumina technology provided whole genome sequences for genome nomenclature, antimicrobial resistance gene prediction, Single Nucleotide Polymorphism (SNP) phylogeny, and multi-locus sequence typing via publicly available bioinformatics pipelines. Initial biochemical delineation often misclassifiedEnterobacter, necessitating whole-genome sequencing for accurate classification. Among 98Enterobacterreceived,Enterobacter hormaecheisubspeciesxiangfangensispredominated (43), followed by otherE. hormacheisubspecies (18),E. cloacae(26),E. roggenkampii(4),E. bugandensis(3),E. kobei(2),E. asburiae(1) andE. cancerogenous(1). Cephalosporins, aminoglycoside, chloramphenicol, macrolide, and carbapenem resistance inE. hormaecheiwas attributed to known resistance genes. They belonged to clusters III, IV, and VIII based onhsp60typing and clades A, B, C, and D according to Sutton and Co’s nomenclature. These isolates and otherEnterobacterspecies recently reported from Nigeria reveal extensiveE. hormaecheidiversity, as well as clusters representing potential outbreaks. Enterobacter hormaechei, often misidentified and rarely reported from Nigeria, is this study’s most common blood culture isolatedEnterobacterspp. Uncovering underappreciated species as important bloodstream pathogens and retrospective detection of likely outbreaks emphasise the value of genomic surveillance in resource-limited settings.DATA SUMMARYAll sequence reads were submitted to the European Nucleotide Archive (ENA) under the project ID PRJEB29739 (https://www.ebi.ac.uk/ena/browser/view/PRJEB29739). Accessions can be found in Table S1.IMPACT STATEMENTAccurate identification ofEnterobacteris essential in healthcare settings as misidentification can lead to selecting antimicrobials to the genus is intrinsically resistant resistant before susceptibility testing results are available. Also, misidentification can compromise microbiology support for infection prevention and control. We show thatE. hormaechei, which is never reported from clinical laboratories in Nigeria, is frequently misidentified using conventional methods like tube- or strip biochemical testing and VITEK systems. Whole genome sequence data demonstrates thatE. hormaecheiandE. cloacaeare the most commonEnterobacterisolated from bloodstream infections in Nigeria. Enhanced identification methods for surveillance play pivotal roles in improving patient care, optimising antibiotic stewardship, and combating the evolving challenges posed by this pathogen. Overall, this study reveals the effectiveness of WGS in correctly identifying this important pathogen.