bioRxiv Science⌕ Search

Biology subjects

Bentley, S.

Publications and source records attributed to Bentley, S..

2 recordsLinked to original sources

Quantifying the effects of antibiotic resistance and within-host competition on strain fitness in Streptococcus pneumoniae

Competition plays a key role in shaping the structure and diversity of bacterial populations. In many clinically important bacterial species, strains compete at multiple scales: at the between-host scale for new hosts to colonise, and at the within-host scale during co-colonisation. Characterising these multiple facets of competition plays an important role in understanding bacterial ecology. This is particularly relevant for antibiotic resistance, where competition between antibiotic-susceptible and resistant strains determines resistance dynamics. In this work, we perform survival analyses on a large longitudinal dataset of Streptococcus pneumoniae carriage to quantify how within-host competition affects the rates of clearance and establishment of pneumococcal strains. We find that the presence of a within-host competitor is associated with a 33% increase in clearance and a 54% reduction in establishment. Priority effects and serotype differences partially predict the outcomes of this within-host competition. Further, we quantify the effects of antibiotic resistance on betweenand within-host components of fitness. Antibiotic consumption is associated with increased clearance rate for both susceptible and resistant strains, albeit to a higher extent in susceptible strains. In the absence of antibiotics, we find some evidence that resistance is associated with increased susceptibility to within-host competition, suggesting a fitness cost of resistance. Overall, our work provides quantitative insights into pneumococcal competition across scales and the role of this competition in shaping pneumococcal epidemiology.

ecology↗

The contribution of genetic variation of Streptococcus pneumoniae to the clinical manifestation of invasive pneumococcal disease

BackgroundDifferent clinical manifestations of invasive pneumococcal disease (IPD) have thus far mainly been explained by patient characteristics. Here we studied the contribution of pneumococcal genetic variation to IPD phenotype.\n\nMethodsThe index cohort consisted of 349 patients admitted to two Dutch hospitals between 2000-2011 with pneumococcal bacteraemia. We performed genome-wide association studies to identify pneumococcal lineages, genes and allelic variants associated with 23 clinical IPD phenotypes. The identified associations were validated in a nationwide (n=482) and a post-pneumococcal vaccination cohort (n=121). The contribution of confirmed pneumococcal genotypes to the clinical IPD phenotype, relative to known clinical predictors, was tested by regression analysis.\n\nFindingsThe presence of pneumococcal gene slaA was a nationwide confirmed independent predictor of meningitis (OR=10.5, p=0.001), as was sequence cluster 9 (OR=3.68, p=0.057). A set of 4 pneumococcal genes co-located on a prophage was a confirmed independent predictor of 30-day mortality (OR=3.4, p=0.003). We could detect the pneumococcal variants of concern in these patients blood samples by molecular amplification. In the post-vaccination cohort where the distribution of both patient characteristics and pneumococcal serotypes had changed, the relative importance of the prophage was no longer supported.\n\nInterpretationKnowledge of pneumococcal genotypic variants improved our clinical risk assessment for detrimental manifestations of IPD. This provides us with novel opportunities to target, anticipate or avert the pathogenic effects that are related to particular pneumococcal variants. Therefore, future diagnostics should facilitate prompt appreciation of pathogen diversity in clinical sepsis management. Ongoing surveillance is warranted to monitor the clinical value of information on pathogen variants in dynamic microbial and susceptible host populations.\n\nFundingNone.

microbiology↗