Essack, S. Y. | Search bioRxiv

bioRxiv2021

Comparative Genome Analysis Reveals Human Pathogenic Potential of ESBL-Escherichia coli Isolated from Swine Microbiomes

BackgroundExtended-spectrum {beta}-lactamase-producing E. coli (ESBL-Ec) harbouring virulence genes in the microbiome of food animals could likely threaten human health but is poorly understood in Cameroon and South Africa. Here, we assessed the resistome, virulome and mobilome of ESBL-Ec isolated from swine microbiomes in these countries, using whole genome sequencing (WGS). Materials/methodsEleven clonally-related phenotypic ESBL-Ec isolates were subjected to WGS. The isolates were de novo assembled using the CLC Genomics Workbench and SPAdes while RAST and PROKKA were used for annotation of the assembled contigs. Prediction of antibiotic resistance genes, virulence factors and plasmids was performed using ResFinder, VirulenceFinder and PlasmidFinder, respectively. ResultsDiverse STs were detected with sequence types ST2144 and ST88 predominating and blaCTX-M-15 (55%) as principal ESBL genes. Although the isolates belonged mainly to commensal phylogroups A/B1 (45/28.3%) and C (18.18%), all harboured at least three extraintestinal pathogenic E. coli (ExPEC) VFs with one isolate harbouring up to 18 ExPEC VFs. ConclusionThe resistance and pathogenic potential of ESBL-Ec colonizing the gut microbiota of swine in both countries demonstrate the urgent need to implement effective strategies to contain the dissemination of virulent ESBL-Ec through the food chain in Cameroon and South Africa.

genomics↗

bioRxiv2018

In Vitro Potentiation of Carbapenems with Tannic Acid Against Carbapenemase Producing Enterobacteriaceae: Exploring Natural Products as Potential Carbapenemase Inhibitors

Resistance to antibiotics is increasing worldwide, necessitating urgent action to sustain the efficacy of existing antibiotics in clinical use. We show that tannic acid (TA) in combination with carbapenems can reduce and/or reverse the minimum inhibitory concentrations (MICs) of carbapenems to susceptible values in Enterobacteriaceae that express class A and B carbapenemases. MICs of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TA-carbapenemases inhibition assays and computational studies were undertaken to determine the effect of TA on carbapenem susceptibility in Enterobacteriaceae. TA had the greatest effect on metallo-{beta}-lactamases (MBLs) followed by class A serine-{beta}-lactamases (SBLs). Antibiotic susceptibility testing showed that TA reversed the MICs of MBLs to susceptible values whilst substantially reducing the MICs of SBLs (class A). Tolerable cytotoxicity effect was observed for the concentrations tested. TA inhibited enzymes with a marked difference between {approx}50% inhibition (IC50) for NDM-1 and KPC-2. Computational studies including molecular docking, molecular dynamics simulations and binding free energy calculations showed that TA interact with both MBLs and SBLs hydrophobic sites. Moreover, TA had a stronger binding affinity for MBLs than SBLs as the MBLs, specifically VIM-1 and NDM-1, interact with a larger number of their catalytic active-site residues than that of OXA- 48 and KPC-2. These in vitro evaluations together with computational simulation explain the potentiating effect of TA toward carbapenems against carbapenem-resistance enterobacteriaceae. This study proposes TA as a promising adjuvant for MBLs and SBLs.

microbiology↗