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Biology subjects

Hadjirin, N. F.

Publications and source records attributed to Hadjirin, N. F..

3 recordsLinked to original sources

Development of a core genome multilocus sequence typing (cgMLST) scheme and life identification number (LIN) code classification system for Staphylococcus aureus

Staphylococcus aureus infects both humans and animals, and antimicrobial resistance, including multidrug resistance, complicates treatment of S. aureus infections. Understanding S. aureus population structure and the distribution of genetic lineages is central to understanding the biology, epidemiology, and pathogenesis of this organism. This study exploited a large, publicly available dataset of nearly 27,000 S. aureus genomes to: i) develop a core genome multilocus sequence type (cgMLST) scheme; ii) stratify hierarchical clusters based on allelic similarity thresholds; and iii) define the clusters with a life identification number (LIN) code classification system. The cgMLST scheme characterised allelic variation at 1,716 core gene loci, and 13 classification thresholds were defined, which discriminated S. aureus variants across a range of genetic similarity thresholds. LIN code lineages and clonal complexes defined by seven-locus multilocus sequence typing were highly concordant, but the LIN codes permitted a wider range of genetic discrimination among S. aureus genomes. This S. aureus cgMLST scheme and LIN code system is a high-resolution, stable genotyping tool that enables detailed genomic analyses of S. aureus.

genomics↗

The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs

The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species this can affect the health of humans as well as livestock. Here we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of Streptococcus suis, a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of S. suis emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of S. suis and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of S. suis is yet to be fully realised.

evolutionary biology↗

Linking phenotype, genotype and ecology: antimicrobial resistance in the zoonotic pathogen Streptococcus suis

Antimicrobial resistance (AMR) is among the gravest threats to human health and food security worldwide. Pigs receive more antimicrobials than most other livestock, and are a known source of zoonotic disease. We studied AMR in Streptococcus suis, a commensal found in most pigs, but which can also cause serious disease in both pigs and humans. We obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 antibiotics, across a panel of 678 isolates, from the major pig-producing regions of the world. For several drugs, there was no natural separation into "resistant" and "susceptible", highlighting the need to treat MIC as a quantitative trait. We found differences in MICs between countries, consistent with their patterns of antimicrobial usage. AMR levels were high even for drugs not used to treat S. suis, with many multi-drug resistant isolates. And similar levels of resistance were found in pigs and humans from zoonotic regions. We next used whole genome sequences for each isolate to identify 43 candidate resistance determinants, 22 of which were novel in S. suis. The presence of these determinants explained most of the variation in MIC. But there were also complications, including epistatic interactions, where known resistance alleles had no effect in some genetic backgrounds. Beta-lactam resistance involved many variants of small effect, appearing in a characteristic order. Our results confirm the potential for genomic data to aid in the fight against AMR, but also demonstrate that it cannot be tackled one species or one drug at a time.

microbiology↗