Biology subjects

Peacock, S.

Publications and source records attributed to Peacock, S..

4 recordsLinked to original sources

bioRxiv2021

Significant Variability exists in the Toxicity of Global Methicillin-resistant Staphylococcus aureus Lineages.

Staphylococcus aureus is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant S. aureus (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI). These infections are primarily toxin driven, leading to the suggestion that hyper-virulent lineages/multi-locus sequence types (STs) exist. To examine this, we compared the toxic activity of 475 MRSA isolates representing five major MRSA STs (ST22, ST93, ST8, ST239 and ST36) by employing a monocyte-macrophage THP-1 cell line as a surrogate for measuring gross cytotoxicity. We demonstrate that while certain MRSA STs contain highly toxic isolates, there is such variability within lineages to suggest that this aspect of virulence should not be inferred from the genotype of any given isolate. Furthermore, by interrogating the accessory gene regulator (Agr) sequences in this collection we identified several Agr mutations that were associated with reduced toxicity. Interestingly, the majority of isolates that were attenuated in toxin production contained no mutations in the agr locus, indicating a role of other undefined genes in S. aureus toxin regulation.

microbiology↗

bioRxiv2019

Genomic surveillance of Escherichia coli ST131 identifies local expansion and serial replacement of subclones

Escherichia coli sequence type 131 (ST131) is a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. Here, we investigated an outbreak of E. coli ST131 producing extended spectrum {beta}-lactamases (ESBLs) in a long-term care facility (LTCF) in Ireland by combining data from this LTCF (n=69) with other Irish (n=35) and global (n=690) ST131 genomes to reconstruct the evolutionary history and understand changes in population structure and genome architecture over time. This required a combination of short and long-read genome sequencing, de novo assembly, read mapping, ESBL gene screening, plasmid alignment and temporal phylogenetics. We found that clade C was the most prevalent (686 out of 794 isolates, 86%) of the three major ST131 clades circulating worldwide (A, B, C), and was associated with the presence of different ESBL alleles, diverse plasmids and transposable elements. Clade C was estimated to have emerged in [~]1985 and subsequently acquired different ESBL gene variants (blaCTX-M-14 vs blaCTX-M-15). An ISEcp1- mediated transposition of the blaCTX-M-15 gene further increased the diversity within Clade C. We discovered a local clonal expansion of a rare C2 lineage (C2_8) with a chromosomal insertion of blaCTX-M-15 at the mppA gene. This was acquired from an IncFIA plasmid. The C2_8 lineage clonally expanded in the Irish LTCF from 2006, displacing the existing C1 strain (C1_10) and highlighting the potential for novel ESBL-producing ST131 with a distinct genetic profile to cause outbreaks strongly associated with specific healthcare environments.\n\nImportanceExtraintestinal pathogenic E. coli (ExPEC) ST131 is adapting in the context of antibiotic exposure, resulting in a pandemic with distinct genetic subtypes. Here, we track the evolution of antibiotic-resistance gene variants originally discovered in an ExPEC ST131 outbreak that was identified in a LTCF in Ireland. Analysis of 794 global ST131 genomes show that subclade C1 was associated with the initial infection outbreak, but that a new lineage from subclade C2 successfully displaced C1. This genetically distinct C2 subclade with a chromosomal insertion of a key antibiotic-resistance gene had clonally expanded within the LTCF. We provide new insights into the timing of genetic events driving the diversification of C2 subclades to show that that outbreak C2 strain likely evolved elsewhere before spreading to the LTCF. This study highlights the scope of antibiotic-resistance gene rearrangement within ST131, reinforcing the need to integrate genomic, epidemiological and microbiological approaches to understand ST131 transmission.

genomics↗

bioRxiv2019

Genetic variation associated with infection and the environment in the accidental pathogen Burkholderia pseudomallei

The environmental bacterium Burkholderia pseudomallei causes melioidosis, an endemic disease in tropical and sub-tropical countries. This bacterium occupies broad ecological niches ranging from soil, contaminated water, single-cell microbes and plants to human infection. Here, we performed genome-wide association studies for genetic determinants of environmental and human adaptation using a combined dataset of 1,011 whole genome sequences of B. pseudomallei from Northeast Thailand (discovery cohort, number of clinical isolates = 325, environmental isolates =428) and Australia (validation cohort, number of clinical isolates = 185, environmental isolates = 73), representing two major global disease hotspots. With these data, we (i) identified 47 genes from 26 distinct loci associated with clinical or environmental isolates from Thailand and replicated 13 loci in an independent Australian cohort; (ii) outlined the selective pressures on the genetic loci (dN/dS) and the frequency at which they had been gained or lost throughout their evolutionary history, reflecting the bacterial adaptability to a wide range of ecological niches; and (iii) highlighted loci implicated in human disease.

microbiology↗

bioRxiv2018

Signatures of negative frequency dependent selection in colonisation factors and the evolution of a multi-drug resistant lineage of Escherichia coli

Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multi-drug resistant (MDR) strains of extra-intestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution towards separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonisation and virulence factors. We further demonstrate that negative frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen.

microbiology↗