Biology subjects

Garcia, V.

Publications and source records attributed to Garcia, V..

4 recordsLinked to original sources

bioRxiv2018

De novo mutations drive the spread of macrolide resistant Mycoplasma genitalium: mathematical modelling study

BackgroundThe rapid spread of azithromycin resistance in sexually transmitted Mycoplasma genitalium infections is a growing concern. It is not yet clear to what degree macrolide resistance in M. genitalium results from the emergence of de novo mutations or the transmission of resistant strains.\n\nMethodsWe analyzed epidemiological data and developed a compartmental model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial-resistant M. genitalium. We fitted the model to data from France, Denmark and Sweden and estimated treatment rates of infected individuals and the time point of azithromycin introduction.\n\nResultsWe found a high probability of de novo resistance (12%, 95% CI 8-17%), which is responsible for the observed rapid spread of antimicrobial resistant M. genitalium. The estimated per capita treatment rate in France was lower than in Denmark and Sweden but confidence intervals for the three estimates overlap. The estimated dates of introduction of azithromycin in each country are consistent with published reports.\n\nConclusionsSince de novo resistance is the main driver of macrolide resistance in M. genitalium, blind treatment of urethritis with azithromycin is not recommended. Clinical management strategies for M. genitalium should limit the unnecessary use of macrolides.

microbiology↗

bioRxiv2018

Accounting for programmed ribosomal frameshifting in the computation of codon usage bias indices

Experimental evidence shows that synonymous mutations can have important consequences on genetic fitness. Many organisms display codon usage bias (CUB), where synonymous codons that are translated into the same amino acid appear with distinct frequency. CUB is thought to arise from selection for translational efficiency and accuracy, termed the translational efficiency hypothesis (TEH). Indeed, CUB indices correlate with protein expression levels, which is widely interpreted as evidence for translational selection. However, these tests neglect -1 programmed ribosomal frameshifting (-1 PRF), an important translational disruption effect found across all organisms of the tree of life. Genes that contain -1 PRF signals should cost more to express than genes without. Thus, CUB indices that do not consider -1 PRF may overestimate genes true adaptation to translational efficiency and accuracy constraints. Here, we first investigate whether -1 PRF signals do indeed carry such translational cost. We then propose two corrections for CUB indices for genes containing -1 PRF signals. We retest the TEH under these corrections. We find that the correlation between corrected CUB index and protein expression remains intact for most levels of uniform -1 PRF efficiencies, and tends to increase when these efficiencies decline with protein expression. We conclude that the TEH is strengthened and that -1 PRF events constitute a promising and useful tool to examine the relationships between CUB and selection for translation efficiency and accuracy.

genetics↗

bioRxiv2017

Modeling the consequences of regional heterogeneity in human papillomavirus (HPV) vaccination uptake on transmission in Switzerland

BackgroundCompleted human papillomavirus (HPV) vaccination by age 16 years among women in Switzerland ranges from 17 to 75% across 26 cantons. The consequences of regional heterogeneity in vaccination coverage on transmission and prevalence of HPV-16 are unclear.\n\nMethodsWe developed a deterministic, population-based model that describes HPV-16 transmission among young adults within and between the 26 cantons of Switzerland. We parameterized the model using sexual behavior data from Switzerland and data from the Swiss National Vaccination Coverage Survey. First, we investigated the general consequences of heterogeneity in vaccination uptake between two sub-populations. We then compared the predicted prevalence of HPV-16 after the introduction of heterogeneous HPV vaccination uptake in all of Switzerland with homogeneous vaccination at an uptake that is identical to the national average (52%).\n\nResultsHPV-16 prevalence in women is 3.34% when vaccination is introduced and begins to diverge across cantons, ranging from 0.14 to 1.09% after 15 years of vaccination. After the same time period, overall prevalence of HPV-16 in Switzerland is only marginally higher (0.55 %) with heterogeneous vaccination uptake than with homogeneous uptake (0.49%). Assuming inter-cantonal sexual mixing, cantons with low vaccination uptake benefit from a reduction in prevalence at the expense of cantons with high vaccination uptake.\n\nConclusionsRegional variations in uptake diminish the overall effect of vaccination on HPV-16 prevalence in Switzerland, although the effect size is small. Cantonal efforts towards HPV-prevalence reduction by increasing vaccination uptake are impaired by cantons with low vaccination uptake. Harmonization of cantonal vaccination programs would reduce inter-cantonal differences in HPV-16 prevalence.

epidemiology↗

bioRxiv2016

Finite-sites multiple mutations interference gives rise to wavelet-like oscillations of multilocus linkage disequilibrium

Within-host adaptation of pathogens such as human immunodeficiency virus (HIV) often occurs at more than two loci. Multiple beneficial mutations may arise simultaneously on different genetic backgrounds and interfere, affecting each other's fixation trajectories. Here, we explore how these adaptive dynamics are mirrored in multilocus linkage disequilibrium (MLD), a measure of multi-way associations between alleles. In the parameter regime corresponding to HIV, we show that deterministic early infection models induce MLD to oscillate over time in a wavelet-like fashion. We find that the frequency of these oscillations is proportional to the rate of adaptation. This signature is robust to drift, but can be eroded by high variation in fitness effects of beneficial mutations. Our findings suggest that MLD oscillations could be used as a signature of interference among multiple equally advantageous mutations and may aid the interpretation of MLD in data.

genetics↗