Panton–Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS

Young, Bernadette C.; Earle, Sarah G; Soeng, Sona; Sar, Pinaki; Kumar, Varun; Hor, Songly; Sar, Vuthy; Bousfield, Rachel; Sanderson, Nicholas; Barker, Leanne; Stoesser, Nicole; Emary, Katherine R. W.; Parry, Christopher M.; Nickerson, Emma K.; Turner, Paul; Bowden, Rory; Crook, Derrick W.; Wyllie, David; Day, Nicholas P. J.; Wilson, Daniel J.; Moore, Catrin E.

doi:10.7554/elife.42486

Cited by 59 publications

(69 citation statements)

References 58 publications

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“…Successful applications of mGWAS include identifying genetic determinants of pyomyositis in Staphylococcus aureus (Young et al, 2019) which revealed that the presence of Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis. In another study, showed that variations in Streptococcus pneumoniae explain large amounts of the invasiveness potential but have no effect on severity of pneumococcal meningitis.…”

Section: Introductionmentioning

confidence: 99%

Current Affairs of Microbial Genome-Wide Association Studies: Approaches, Bottlenecks and Analytical Pitfalls

et al. 2020

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Microbial genome-wide association studies (mGWAS) are a new and exciting research field that is adapting human GWAS methods to understand how variations in microbial genomes affect host or pathogen phenotypes, such as drug resistance, virulence, host specificity and prognosis. Several computational tools and methods have been developed or adapted from human GWAS to facilitate the discovery of novel mutations and structural variations that are associated with the phenotypes of interest. However, no comprehensive, end-to-end, user-friendly tool is currently available. The development of a broadly applicable pipeline presents a real opportunity among computational biologists. Here, (i) we review the prominent and promising tools, (ii) discuss analytical pitfalls and bottlenecks in mGWAS, (iii) provide insights into the selection of appropriate tools, (iv) highlight the gaps that still need to be filled and how users and developers can work together to overcome these bottlenecks. Use of mGWAS research can inform drug repositioning decisions as well as accelerate the discovery and development of more effective vaccines and antimicrobials for pressing infectious diseases of global health significance, such as HIV, TB, influenza, and malaria.

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Section: Introductionmentioning

confidence: 99%

Current Affairs of Microbial Genome-Wide Association Studies: Approaches, Bottlenecks and Analytical Pitfalls

et al. 2020

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“…With increasing sequencing data available, this is being complemented by genome-wide association studies (GWAS) (Chen and Shapiro 2015;Falush 2016). Several bacterial GWAS have been reported for S. aureus (Alam et al 2014;Laabei et al 2014;Baines et al 2015;Young et al 2019) and other species (Howell et al 2014;Earle et al 2016;Coll et al 2017). These have largely addressed pathogenicity and virulence (Howell et al 2014;Laabei et al 2014;Lees et al 2016Lees et al , 2019, and antibiotic resistance (Alam et al 2014;Desjardins et al 2016;Earle et al 2016;Coll et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Contrasting approaches to genome-wide association studies impact the detection of resistance mechanisms in Staphylococcus aureus

Wheeler

Reuter

Chewapreecha

et al. 2019

Preprint

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Rapid detection of antibiotic resistance using whole-genome sequencing (WGS) could improve clinical outcomes and limit the spread of resistance. For this to succeed, we need an accurate way of linking genotype to phenotype, that identifies new resistance mechanisms as they appear. To assess how close we are to this goal, we characterized antimicrobial resistance determinants in >4,000 Staphylococcus aureus genomes of isolates associated with bloodstream infection in the United Kingdom and Ireland. We sought to answer three questions: 1) how well did known resistance mechanisms explain phenotypic resistance in our collection, 2) how many previously identified resistance mechanisms appeared in our collection, and 3) how many of these were detectable using four contrasting genome-wide association study (GWAS) methods. Resistance prediction based on the detection of known resistance determinants was 98.8% accurate. We identified challenges in correcting for population structure, clustering orthologous genes, and identifying causal mechanisms in rare or common phenotypes, which reduced the recovery of known mechanisms. Limited sensitivity and specificity of these methods made prediction using GWAS-discovered hits alone less accurate than using literature-derived genetic determinants. However, GWAS methods identified novel mutations associated with resistance, including five mutations in rpsJ, which improved tetracycline resistance prediction for 28 isolates, and a T118I substitution in fusA which resulted in better fusidic acid resistance prediction for 5 isolates. Thus, GWAS approaches in conjunction with phenotypic testing data can support the development of comprehensive databases to enable real-time use of WGS for patient management.

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“…Accurate characterization of large numbers of microbial genomes is becoming increasingly important in microbiology. For example, bacterial genome-wide association studies (bGWAS) rely on the sequencing of large numbers of samples to correlate genetic variants to phenotypes such as antibiotic resistance or virulence [1][2][3]. Further examples are phylogenetic analyses and quality assurance in industrial microbiology [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Ultraplexing: increasing the efficiency of long-read sequencing for hybrid assembly with k-mer-based multiplexing

2020

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Hybrid genome assembly has emerged as an important technique in bacterial genomics, but cost and labor requirements limit large-scale application. We present Ultraplexing, a method to improve per-sample sequencing cost and hands-on time of Nanopore sequencing for hybrid assembly by at least 50% compared to molecular barcoding while maintaining high assembly quality. Ultraplexing requires the availability of Illumina data and uses inter-sample genetic variability to assign reads to isolates, which obviates the need for molecular barcoding. Thus, Ultraplexing can enable significant sequencing and labor cost reductions in large-scale bacterial genome projects.

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Panton–Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS

Cited by 59 publications

References 58 publications

Current Affairs of Microbial Genome-Wide Association Studies: Approaches, Bottlenecks and Analytical Pitfalls

Current Affairs of Microbial Genome-Wide Association Studies: Approaches, Bottlenecks and Analytical Pitfalls

Contrasting approaches to genome-wide association studies impact the detection of resistance mechanisms in Staphylococcus aureus

Ultraplexing: increasing the efficiency of long-read sequencing for hybrid assembly with k-mer-based multiplexing

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