Contrasting evolution of virulence and replication rate in an emerging bacterial pathogen

This is the final version. Available on open access from the National Academy of Sciences via the DOI in this recordData deposition: Data reported in this paper have been deposited in Dryad Digital Repository (doi:10.5061/dryad.km3109k).Host resistance through immune clearance is predicted to favor pathogens that are able to transmit faster and are hence more virulent. Increasing pathogen virulence is, in turn, typically assumed to be mediated by increasing replication rates. However, experiments designed to test how pathogen virulence and replication rates evolve in response to increasing host resistance, as well as the relationship between the two, are rare and lacking for naturally evolving host–pathogen interactions. We inoculated 55 isolates of Mycoplasma gallisepticum, collected over 20 y from outbreak, into house finches (Haemorhous mexicanus) from disease-unexposed populations, which have not evolved protective immunity to M. gallisepticum. We show using 3 different metrics of virulence (body mass loss, symptom severity, and putative mortality rate) that virulence has increased linearly over >150,000 bacterial generations since outbreak (1994 to 2015). By contrast, while replication rates increased from outbreak to the initial spread of resistance (1994 to 2004), no further increases have occurred subsequently (2007 to 2015). Finally, as a consequence, we found that any potential mediating effect of replication rate on virulence evolution was restricted to the period when host resistance was initially increasing in the population. Taken together, our results show that pathogen virulence and replication rates can evolve independently, particularly after the initial spread of host resistance. We hypothesize that the evolution of pathogen virulence can be driven primarily by processes such as immune manipulation after resistance spreads in host populations.Natural Environment Research Council (NERC

Low prevalence of coagulation F2 and F5 polymorphisms in mothers and children in a large cohort of patients with neonatal arterial ischemic stroke

International audienc

Rapid antagonistic coevolution in an emerging pathogen and its vertebrate host

This is the final version of the article. Available from Elsevier via the DOI in this record.Host-pathogen coevolution is assumed to play a key role in eco-evolutionary processes, including epidemiological dynamics and the evolution of sexual reproduction [1-4]. Despite this, direct evidence for host-pathogen coevolution is exceptional [5-7], particularly in vertebrate hosts. Indeed, although vertebrate hosts have been shown to evolve in response to pathogens or vice versa [8-12], there is little evidence for the necessary reciprocal changes in the success of both antagonists over time [13]. Here, we generate a time-shift experiment to demonstrate adaptive, reciprocal changes in North American house finches (Haemorhous mexicanus) and their bacterial pathogen, Mycoplasma gallisepticum [14-16]. Our experimental design is made possible by the existence of disease-exposed and unexposed finch populations, which were known to exhibit equivalent responses to experimental inoculation until the recent spread of genetic resistance in the former [14, 17]. While inoculation with pathogen isolates from epidemic outbreak caused comparable sub-lethal eye-swelling in hosts from exposed (hereafter adapted) and unexposed (hereafter ancestral) populations, inoculation with isolates sampled after the spread of resistance were threefold more likely to cause lethal symptoms in hosts from ancestral populations. Similarly, the probability that pathogens successfully established an infection in the primary host and, before inducing death, transmitted to an uninfected sentinel was highest when recent isolates were inoculated in hosts from ancestral populations and lowest when early isolates were inoculated in hosts from adapted populations. Our results demonstrate antagonistic host-pathogen coevolution, with hosts and pathogens displaying increased resistance and virulence in response to each other over time.This research was supported by a Natural Environment Research Council standard grant to C.B. (NE/M00256X)

The moderate drift towards less tetracycline-susceptible isolates of contagious agalactia causative agents might result from different molecular mechanisms.

©2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Veterinary Microbiology. To access the final edited and published work see https://doi.org/10.1016/j.vetmic.2018.05.001Contagious agalactia is a mycoplasmosis that affects small ruminants, is associated with loss of milk production and high morbidity rates, and is highly deleterious to dairy industries. The etiological agents are four mycoplasma (sub)species, of which the relative importance depends on the countries and the animal host. Tetracyclines are non 23 expensive, broad-spectrum antimicrobials and are often used to control mastitis in dairy herds. However, the in vitro efficiency of tetracyclines against each of the etiological agents of contagious agalactia has been poorly assessed. The aims of this study were i) to compare the tetracycline susceptibilities of various field isolates, belonging to different mycoplasma (sub)species and subtypes, collected over the years from different clinical contexts in France or Spain, and ii) to investigate the molecular mechanisms behind the decreased susceptibility of some isolates to tetracyclines. The Minimum Inhibitory Concentrations (MICs) of tetracyclines were determined in vitro on a set of 120 isolates. Statistical analyses were run to define the significance of any observed differences in MICs distribution. As mutations in the genes encoding the ttracycline targets (rrs loci) are most often associated with increased tetracycline MICs in animal mycoplasmas, these genes were sequenced. The loss of susceptibility to tetracyclines after year 2010 is not significant and recent MICs are higher in M. agalactiae, especially isolates from ovine mastitis cases, than in other etiological agents of contagious agalactia. The observed increases in MICs were not always associated with mutations in the rrs alleles which suggests the existence of other resistance mechanisms yet to be decipher

Predation on migrating eels (Anguilla anguilla L.) from the Western Mediterranean

Nineteen female silver European eels (Anguilla anguilla L.) were tagged with satellite tags and released in the Gulf of Lion in the Mediterranean during the migration seasons 2013 and 2015. Sixteen tags transmitted data: five in the Atlantic Ocean, and eleven in the Mediterranean. Of those, 50% of migrating eels were consumed by marine mammals in each year, all in the Mediterranean. The diving behaviour recorded by the tags after the eels were consumed indicated that the most likely predators were deep diving toothed whales. Measurements of the acoustic target strength of the tag showed a negligible effect on the detectability by whale biosonar. Overall, the observed predation rate was similar to that reported for eels escaping into the Atlantic. However, unlike eels in the Atlantic, which are most vulnerable to predators in the first week of escapement as they traverse the continental shelf and before they reach the refuge of the deep ocean, eels escaping from the Mediterranean were predated in deep water, months after release, likely as a consequence of their migration within a relatively narrow and deep corridor in the Alboran Sea. This emphasises the challenge of accounting for natural mortality in management plans for the long-term recovery of the European eel

Integration of formal fault analysis in ASSERT: Case studies and lessons learnt

International audienceThe ASSERT European Integrated Project (Automated proof-based System and Software Engineering for Real-Time systems; EC FP6, IST-004033) has investigated, elaborated and experimented advanced methods based on the AltaRica language and support tool OCAS for architecture and fault approach propagation description analysis, and integrated in the complete ASSERT process. The paper describes lessons learnt from three case studies: safety critical spacecraft, autonomous deep exploration spacecraft, and civil aircraft