Biology subjects

Mmatli, M.

Publications and source records attributed to Mmatli, M..

3 recordsLinked to original sources

bioRxiv2024

Plasmid-borne mcr-1 and Replicative Transposition of Episomal and Chromosomal blaNDM-1, blaOXA-69, and blaOXA-23 Carbapenemases in a Clinical Acinetobacter baumannii Isolate

BackgroundA multidrug-resistant clinical A. baumannii isolate with resistance to most antibiotics was isolated from a patient at an intensive care unit. The genetic environment, transcriptome, mobile, and resistome were characterized. MethodThe MicroScan system, disc diffusion, and broth microdilution were used to determine the resistance profile of the isolate. A multiplex PCR assay was also used to screen for carbapenemases and mcr-1 to -5 resistance genes. Efflux-pump inhibitors were used to evaluate efflux activity. The resistome, mobilome, epigenome, and transcriptome were characterized. Results & conclusionThere was phenotypic resistance to 22 of the 25 antibiotics tested, intermediate resistance to levofloxacin and nalidixic acid, and susceptibility to tigecycline, which corresponded to the 27 resistance genes found in the genome, most of which occurred in multiple copies through replicative transposition. A plasmid-borne (pR-B2.MM_C3) mcr-1 and chromosomal blaPER-7, blaOXA-69, blaOXA-23 (three copies), blaADC-25, blaTEM-1B, and blaNDM-1 were found within composite transposons, ISs, and/or class 1 and 2 integrons on genomic islands. Types I and II methylases and restriction endonucleases were in close synteny to these resistance genes within the genomic islands; chromosomal genomic islands aligned with known plasmids. There was a closer evolutionary relationship between the strain and global strains but not local or regional strains; the resistomes also differed. Significantly expressed/repressed genes (6.2%) included resistance genes, hypothetical proteins, mobile elements, methyltransferases, transcription factors, membrane and efflux proteins. The genomic evolution observed in this strain explains its adaptability and pandrug resistance and shows its genomic plasticity on exposure to antibiotics.

genomics↗

bioRxiv2023

Molecular Epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa Hospital, South Africa

BackgroundAn outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. MethodsBacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. ResultsThe outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemase-positive, but four blaOXA-48 isolates were susceptible to carbapenems. BlaNDM-1 (n = 13) and blaOXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. ConclusionsThe outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.

microbiology↗

bioRxiv2023

Genomic, Epigenomic, and Transcriptional Characterisation of Carbapenem and Colistin Resistance Mechanisms in Klebsiella pneumoniae and Enterobacter species.

The emergence of colistin and carbapenem-resistant Klebsiella pneumoniae isolates presents a significant global health threat. This study investigates the resistance mechanisms in six K. pneumoniae and four Enterobacter sp. isolates lacking carbapenemases or mcr genes using genomics and transcriptomics. The ten isolates were classified into three categories: non-carbapenemase-producing, carbapenem-resistant strains (n = 4), non-mcr-producing colistin-resistant strains (n = 5), and one isolate susceptible to both antibiotics. The analysis included phenotypic characterization using MicroScan ID/AST, enzyme (MCR and Metallo {beta}-lactamase) and efflux pump inhibition (EPI) assays. Whole-genome sequencing, RNA sequencing, and bioinformatics tools were employed in subsequent analysis. Most of the K. pneumoniae were ST307 with KL102 and O1/O2V2 serotypes. MicroScan revealed multidrug resistance, and AMR analysis identified numerous ARGs in K. pneumoniae. Enterobacter species possessed fewer resistance genes; nevertheless, they encoded virulence factors and gene mutations, potentially impacting the AST profile. K. pneumoniae ARGs were mainly plasmid-borne, with IncFIB(K)/IncFII(K) in Kp_15 harbouring up to nineteen ARGs. Virulence factors included biofilm formation, capsule production, and type IV secretion. Epigenomic investigations revealed prevalent type I (M1.Ecl34977I) and type II (M.Kpn34618Dcm) restriction modification sites. Compared to international isolates, the study isolates phylogenetically clustered more closely with Chinese strains. Transcriptomics showed high efflux pump activity in carbapenem-resistant isolates, confirmed by EPI. Further, mutations were identified in outer membrane proteins. Colistin-resistant isolates exhibited high capsule production, efflux pump, and putative glycotransferase activity, potentially influencing their phenotypes. In conclusion, genomic and transcriptional analyses enhanced our understanding of adaptive mechanisms in clinical multidrug-resistant pathogens, posing significant public health challenges.

molecular biology↗