Bivariate genome-wide association study of the growth plasticity of Staphylococcus aureus in coculture with Escherichia coli

2020 ◽  
Vol 104 (12) ◽  
pp. 5437-5447 ◽  
Author(s):  
Xuyang Zheng ◽  
Jun Bai ◽  
Meixia Ye ◽  
Yanxi Liu ◽  
Yi Jin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial genome-wide association study

2018 ◽  
Author(s):  
Bernadette C Young ◽  
Sarah G Earle ◽  
Sona Soeng ◽  
Poda Sar ◽  
Varun Kumar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Bacterial Genome ◽  
Strong Relationship ◽  
Genome Wide Association ◽  
Tropical Regions ◽  
Genome Wide ◽  
A Genome

AbstractPyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions and predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children in Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p =10-17.9). The signal of association mapped both to the PVL-coding sequence and the sequence immediately upstream. Together these regions explained > 99.9% of heritability. Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on expression of a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.

scholarly journals Genome-Wide Association Study of Staphylococcus aureus Carriage in a Community-Based Sample of Mexican-Americans in Starr County, Texas

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142130 ◽  
Author(s):  
Eric L. Brown ◽  
Jennifer E. Below ◽  
Rebecca S. B. Fischer ◽  
Heather T. Essigmann ◽  
Hao Hu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Association Study ◽  
Mexican Americans ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Community Based ◽  
Genome Wide ◽  
Starr County

scholarly journals Genome wide association study of human bacteremia Escherichia coli isolates identifies genetic determinants for the portal of entry but not fatal outcome

2021 ◽  
Author(s):  
Erick Denamur ◽  
Bénédicte Condamine ◽  
Marina Esposito-Farèse ◽  
Guilhem Royer ◽  
Olivier Clermont ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Association Study ◽  
Patient Outcomes ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Host Factors ◽  
Genome Wide Association ◽  
E Coli ◽  
Genome Wide ◽  
Bacterial Genetic

Escherichia coli is an important cause of bloodstream infections (BSI), which is of concern given its high mortality and increasing worldwide prevalence. Finding bacterial genetic variants that might contribute to patient death is of interest to better understand its mechanism and implement diagnostic methods that specifically look for those factors. E. coli samples isolated from patients with BSI are an ideal dataset to systematically search for those variants, as long as the influence of host factors such as comorbidities are taken into account. Here we performed a genome-wide association study (GWAS) using data from 910 patients with E. coli BSI from hospitals in Paris, France; we looked for associations between bacterial genetic variants and three patient outcomes (death at 28 days, septic shock and admission to intensive care unit), as well as two portals of entry (urinary and digestive tract), using various clinical variables from each patient to account for host factors. We did not find any associations between genetic variants and patient outcomes, potentially confirming the strong influence of host factors in influencing the course of BSI; we however found a strong association between the papGII/papGIII operon and entrance of E. coli through the urinary tract, which demonstrates the power of bacterial GWAS even when applied to actual clinical data. Despite the lack of associations between E. coli genetic variants and patient outcomes, we estimate that increasing the sample size by one order of magnitude could lead to the discovery of some putative causal variants. The adoption of bacterial genome sequencing of clinical isolates might eventually lead to the elucidation of the mechanisms behind BSI progression and the development of sequence-based diagnostics.

scholarly journals Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the hospital environment: a bacterial genome-wide association study

2021 ◽  
Author(s):  
Bernadette C Young ◽  
Chieh-Hsi Wu ◽  
Jane Charlesworth ◽  
Sarah Earle ◽  
James R Price ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Association Study ◽  
Bloodstream Infection ◽  
Genome Wide Association Study ◽  
Nasal Carriage ◽  
Genomic Variation ◽  
Hospital Environment ◽  
Genome Wide Association ◽  
Genome Wide

AbstractBackgroundStaphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease.MethodsTo investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage.ResultsAll major global lineages were represented in both bacteraemia and carriage, with no evidence for different attack rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (p=10−8.9-10−9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10−5.3) as well as the presence of SCCmec (HMP=10−4.4).Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (p=10−7.1-10−19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (p=10−7.2).ConclusionsIn an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment.Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and hospital-associated carriage, suggesting that AMR increases the propensity not only to survive in hospital environments, but also to cause invasive disease.

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