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- Atterby, Clara, et al.
(author)
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The Potential of Isolation Source to Predict Colonization in Avian Hosts : A Case Study in Campylobacter jejuni Strains From Three Bird Species
- 2018
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In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
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Journal article (peer-reviewed)abstract
- Campylobacter jejuni is the primary cause of bacterial gastroenteritis worldwide, infecting humans mostly through consumption of contaminated poultry. C. jejuni is common in the gut of wild birds, and shows distinct strain-specific association to particular bird species. This contrasts with farm animals, in which several genotypes co-exist. It is unclear if the barriers restricting transmission between host species of such specialist strains are related to environmental factors such as contact between host species, bacterial survival in the environment, etc., or rather to strain specific adaptation to the intestinal environment of specific hosts. We compared colonization dynamics in vivo between two host-specific C. jejuni from a song thrush (ST-1304 complex) and a mallard (ST-995), and a generalist strain from chicken (ST-21 complex) in a wild host, the mallard (Anas platyrhynchos). In 18-days infection experiments, the song thrush strain showed only weak colonization and was cleared from all birds after 10 days, whereas both mallard and chicken strains remained stable. When the chicken strain was given 4 days prior to co-infection of the same birds with a mallard strain, it was rapidly outcompeted by the latter. In contrast, when the mallard strain was given 4 days prior to co-infection with the chicken strain, the mallard strain remained and expansion of the chicken strain was delayed. Our results suggest strain-specific differences in the ability of C. jejuni to colonize mallards, likely associated with host origin. This difference might explain observed host association patterns in C. jejuni from wild birds.
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- Berthenet, Elvire, et al.
(author)
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A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk
- 2018
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In: BMC Biology. - : BioMed Central. - 1741-7007. ; 16:1
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Journal article (peer-reviewed)abstract
- BACKGROUND:Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people. Here, we use comparative genomics approaches to understand how genetic variation amongst bacterial strains influences disease progression.RESULTS:We performed a genome-wide association study (GWAS) on 173 H. pylori isolates from the European population (hpEurope) with known disease aetiology, including 49 from individuals with gastric cancer. We identified SNPs and genes that differed in frequency between isolates from patients with gastric cancer and those with gastritis. The gastric cancer phenotype was associated with the presence of babA and genes in the cag pathogenicity island, one of the major virulence determinants of H. pylori, as well as non-synonymous variations in several less well-studied genes. We devised a simple risk score based on the risk level of associated elements present, which has the potential to identify strains that are likely to cause cancer but will require refinement and validation.CONCLUSION:There are a number of challenges to applying GWAS to bacterial infections, including the difficulty of obtaining matched controls, multiple strain colonization and the possibility that causative strains may not be present when disease is detected. Our results demonstrate that bacterial factors have a sufficiently strong influence on disease progression that even a small-scale GWAS can identify them. Therefore, H. pylori GWAS can elucidate mechanistic pathways to disease and guide clinical treatment options, including for asymptomatic carriers.
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- Lu, Yingchang, et al.
(author)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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- Yokoyama, Maho, et al.
(author)
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Epistasis analysis uncovers hidden antibiotic resistance-associated fitness costs hampering the evolution of MRSA
- 2018
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1474-760X. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: Fitness costs imposed on bacteria by antibiotic resistance mechanisms are believed to hamper their dissemination. The scale of these costs is highly variable. Some, including resistance of Staphylococcus aureus to the clinically important antibiotic mupirocin, have been reported as being cost-free, which suggests that there are few barriers preventing their global spread. However, this is not supported by surveillance data in healthy communities, which indicate that this resistance mechanism is relatively unsuccessful. Results: Epistasis analysis on two collections of MRSA provides an explanation for this discord, where the mupirocin resistance-conferring mutation of the ileS gene appears to affect the levels of toxins produced by S. aureus when combined with specific polymorphisms at other loci. Proteomic analysis demonstrates that the activity of the secretory apparatus of the PSM family of toxins is affected by mupirocin resistance. As an energetically costly activity, this reduction in toxicity masks the fitness costs associated with this resistance mutation, a cost that becomes apparent when toxin production becomes necessary. This hidden fitness cost provides a likely explanation for why this mupirocin-resistance mechanism is not more prevalent, given the widespread use of this antibiotic. Conclusions: With dwindling pools of antibiotics available for use, information on the fitness consequences of the acquisition of resistance may need to be considered when designing antibiotic prescribing policies. However, this study suggests there are levels of depth that we do not understand, and that holistic, surveillance and functional genomics approaches are required to gain this crucial information.
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