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Biology subjects

Jamrozy, D. M.

Publications and source records attributed to Jamrozy, D. M..

3 recordsLinked to original sources

Genomic Characterisation of Group B Streptococcus from Argentina: Insights into Prophage Diversity, Virulence Factors and Antibiotic Resistance Genes

Group B Streptococcus (GBS) is a commensal bacterium that can cause severe infections in infants and adults with comorbidities. Resistance and reduced susceptibility to antibiotics is continually on the rise, and vaccines remain in-development. Prophages have been reported to contribute to GBS evolution and pathogenicity. However, no studies are available to date on prophage contribution to the epidemiology of GBS isolates from humans in South America. In the context of an Argentinian multicentric study, we had previously phenotypically characterised 365 human GBS isolates from invasive disease, urinary infections and maternal colonisation. These isolates had been whole genome sequenced and their prophage presence bioinformatically determined. In this study, we genomically characterised the isolates and analysed the prophage content in the context of the epidemiological data. The phylogenetic analysis of the 365 genomes with 103 GBS from public databases revealed that Argentinian GBS were related to isolates from around the world. The most prevalent lineages, independently of the isolate source, were CC23/Ia and CC12/Ib. Genes encoding virulence factors involved in immune response evasion, tissue damage and adherence to host tissues and invasion were found in all of the genomes in accordance with previously described lineage distribution. According to the prevalent capsular types and the distribution of specific virulence factors in Argentinian GBS, over 95% coverage would be expected from the vaccines currently under development. Antibiotic resistance determinants (ARDs) to at least one antibiotic class were found in 90% of the genomes, including novel mutations in pbp2x, while more than 15% carried ARDs to 3 or more classes. GBS collected from urinary infections carried a significantly higher proportion of ARDs to multiple antibiotic classes than the rest of the isolates. A total of 454 prophages were found among the 468 genomes analysed, which were classified into 23 prophage types. Prophage presence exhibited variations based on GBS clonal complex and capsular type. A possible association between an increased GBS pathogenicity and the carriage of prophages with integrase type GBSInt8 and/or the presence of genes that encode the Phox Homology domain has been observed. The highest prevalence of prophages per genome was found in lineages CC17/III and CC19/III, while the lowest amount was observed in CC12/Ib. Overall, the highest density of prophages, virulence factors and ARDs determinants was found in CC19 isolates, mostly of capsular type III, independently of the isolates source. This is the first analysis of the human-associated GBS population in South America based on whole genome sequencing data, which will make a significant contribution to future studies on the global GBS population structure. Data summarySupplementary results and figures can be found in Supplementary Material 1. Supplementary tables can be found in Supplementary Material 2. All datasets analysed in this study are detailed in the Supplementary Materials. Metadata about the genomes analysed can be found in the microreact project created for this study: https://microreact.org/project/gbs-pangenomic-analysis. Impact statementIn Latin America studies on the epidemiology of Group B Streptococcus (GBS) are scarce, especially those describing clonal complex and serotype distribution, and the role of prophages in GBS epidemiology has not been studied. This article addresses the first genomic characterisation of the human-isolated GBS population in Latin America based on whole genome sequencing data, with special focus on the analysis of prophage content. We determine the clonal complex and serotype distribution of 365 GBS isolates collected from clinical samples in an Argentinian multicenter study and analyse the presence of prophages and virulence and antibiotic resistance determinants in the context of the epidemiological data. Through these analyses, we were able to determine how GBS population structure in Argentina differs from other parts of the world and to predict the potential coverage of the in-development GBS vaccines. We also found a possible association between the carriage of certain types of prophages and an increased GBS pathogenicity. In the context of increased global efforts to develop new strategies to prevent GBS infections through vaccine development, this study makes a significant contribution to our understanding of the global GBS population structure.

bioinformatics↗

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↗

One Health genomic surveillance of Escherichia coli demonstrates distinct lineages and mobile genetic elements in isolates from humans versus livestock

Livestock have been proposed as a reservoir for drug-resistant Escherichia coli that infect humans. We isolated and sequenced 431 E. coli (including 155 ESBL-producing isolates) from cross-sectional surveys of livestock farms and retail meat in the East of England. These were compared with the genomes of 1517 E. coli associated with bloodstream infection in the United Kingdom. Phylogenetic core genome comparisons demonstrated that livestock and patient isolates were genetically distinct, indicating that E. coli causing serious human infection do not directly originate from livestock. By contrast, we observed highly related isolates from the same animal species on different farms. Analysis of accessory (variable) genomes identified a virulence cassette associated previously with cystitis and neonatal meningitis that was only present in isolates from humans. Screening all 1948 isolates for accessory genes encoding antibiotic resistance revealed 41 different genes present in variable proportions of humans and livestock isolates. We identified a low prevalence of shared antimicrobial resistance genes between livestock and humans based on analysis of mobile genetic elements and long-read sequencing. We conclude that in this setting, there was limited evidence to support the suggestion that antimicrobial resistant pathogens that cause serious infection in humans originate from livestock.\n\nImportanceThe increasing prevalence of E. coli bloodstream infections is a serious public health problem. We used genomic epidemiology in a One Health study conducted in the East of England to examine putative sources of E. coli associated with serious human disease. E. coli from 1517 patients with bloodstream infection were compared with 431 isolates from livestock farms and meat. Livestock-associated and bloodstream isolates were genetically distinct populations based on core genome and accessory genome analyses. Identical antimicrobial resistance genes were found in livestock and human isolates, but there was little overlap in the mobile elements carrying these genes. In addition, a virulence cassette found in humans isolates was not identified in any livestock-associated isolate. Our findings do not support the idea that E. coli causing invasive disease or their resistance genes are commonly acquired from livestock.

genomics↗