Antimicrobial-Resistant Bacteria Carriage in Rodents According to Habitat Anthropization.

It is increasingly suggested that the dynamics of antimicrobial-resistant bacteria in the wild are mostly anthropogenically driven, but the spatial and temporal scales at which these phenomena occur in landscapes are only partially understood. Here, we explore this topic by studying antimicrobial resistance in the commensal bacteria from micromammals sampled at 12 sites from a large heterogenous landscape (the Carmargue area, Rhone Delta) along a gradient of anthropization: natural reserves, rural areas, towns, and sewage-water treatment plants. There was a positive relationship between the frequency of antimicrobial-resistant bacteria and the level of habitat anthropization. Although low, antimicrobial resistance was also present in natural reserves, even in the oldest one, founded in 1954. This study is one of the first to support the idea that rodents in human-altered habitats are important components of the environmental pool of resistance to clinically relevant antimicrobials and also that a "One Health" approach is required to assess issues related to antimicrobial resistance dynamics in anthropized landscapes.

Staphylococcus aureus Host Spectrum Correlates with Methicillin Resistance in a Multi-Species Ecosystem.

Although antibiotic resistance is a major issue for both human and animal health, very few studies have investigated the role of the bacterial host spectrum in its dissemination within natural ecosystems. Here, we assessed the prevalence of methicillin resistance among Staphylococcus aureus (MRSA) isolates from humans, non-human primates (NHPs), micromammals and bats in a primatology center located in southeast Gabon, and evaluated the plausibility of four main predictions regarding the acquisition of antibiotic resistance in this ecosystem. MRSA strain prevalence was much higher in exposed species (i.e., humans and NHPs which receive antibiotic treatment) than in unexposed species (micromammals and bats), and in NHP species living in enclosures than those in captivity-supporting the assumption that antibiotic pressure is a risk factor in the acquisition of MRSA that is reinforced by the irregularity of drug treatment. In the two unexposed groups of species, resistance prevalence was high in the generalist strains that infect humans or NHPs, supporting the hypothesis that MRSA strains diffuse to wild species through interspecific transmission of a generalist strain. Strikingly, the generalist strains that were not found in humans showed a higher proportion of MRSA strains than specialist strains, suggesting that generalist strains present a greater potential for the acquisition of antibiotic resistance than specialist strains. The host spectrum is thus a major component of the issue of antibiotic resistance in ecosystems where humans apply strong antibiotic pressure.

Multiresistant Enterobacteriaceae in yellow-legged gull chicks in their first weeks of life.

Wild animal species living in anthropogenic areas are commonly carriers of antimicrobial-resistant bacteria (AMRB), but their role in the epidemiology of these bacteria is unclear. Several studies on AMRB in wildlife have been cross-sectional in design and sampled individual animals at only one point in time. To further understand the role of wildlife in maintaining and potentially transmitting these bacteria to humans and livestock, longitudinal studies are needed in which samples are collected from individual animals over multiple time periods. In Europe, free-ranging yellow-legged gulls (Larus michahellis) commonly live in industrialized areas, forage in landfills, and have been found to carry AMRB in their feces. Using bacterial metagenomics and antimicrobial resistance characterization, we investigated the spatial and temporal patterns of AMRB in a nesting colony of yellow-legged gulls from an industrialized area in southern France. We collected 54 cloacal swabs from 31 yellow-legged gull chicks in 20 nests on three dates in 2016. We found that AMRB in chicks increased over time and was not spatially structured within the gull colony. This study highlights the complex occurrence of AMRB in a free-ranging wildlife species and contributes to our understanding of the public health risks and implications associated with ARMB-carrying gulls living in anthropogenic areas.

A population genetic perspective on the origin, spread and adaptation of the human malaria agents Plasmodium falciparum and Plasmodium vivax.

Malaria is considered one of the most important scourges that humanity has faced during its history, being responsible every year for numerous deaths worldwide. The disease is caused by protozoan parasites, among which two species are responsible of the majority of the burden, Plasmodium falciparum and Plasmodium vivax. For these two parasite species, the questions of their origin (how and when they appeared in humans), of their spread throughout the world, as well as how they have adapted to humans have long been of interest to the scientific community. In this paper we review the existing body of knowledge, including current research dealing with these questions, focusing particularly on genetic and genomic analyses of these parasites and comparison with related Plasmodium species infecting other species of host (such as non-human primates).

On the need for integrating cancer into the One Health perspective.

Recent pandemics have highlighted the urgency to connect disciplines studying animal, human, and environment health, that is, the "One Health" concept. The One Health approach takes a holistic view of health, but it has largely focused on zoonotic diseases while not addressing oncogenic processes. We argue that cancers should be an additional key focus in the One Health approach based on three factors that add to the well-documented impact of humans on the natural environment and its implications on cancer emergence. First, human activities are oncogenic to other animals, exacerbating the dynamics of oncogenesis, causing immunosuppressive disorders in wildlife with effects on host-pathogen interactions, and eventually facilitating pathogen spillovers. Second, the emergence of transmissible cancers in animal species (including humans) has the potential to accelerate biodiversity loss across ecosystems and to become pandemic. It is crucial to understand why, how, and when transmissible cancers emerge and spread. Third, translating knowledge of tumor suppressor mechanisms found across the Animal Kingdom to human health offers novel insights into cancer prevention and treatment strategies.

Population genomic evidence of Plasmodium vivax Southeast Asian origin.

Plasmodium vivax is the most common and widespread human malaria parasite. It was recently proposed that P. vivax originates from sub-Saharan Africa based on the circulation of its closest genetic relatives (P. vivax-like) among African great apes. However, the limited number of genetic markers and samples investigated questions the robustness of this hypothesis. Here, we extensively characterized the genomic variations of 447 human P. vivax strains and 19 ape P. vivax-like strains collected worldwide. Phylogenetic relationships between human and ape Plasmodium strains revealed that P. vivax is a sister clade of P. vivax-like, not included within the radiation of P. vivax-like By investigating various aspects of P. vivax genetic variation, we identified several notable geographical patterns in summary statistics in function of the increasing geographic distance from Southeast Asia, suggesting that P. vivax may have derived from a single area in Asia through serial founder effects.

Author Correction: Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The role of innate immunity in the protection conferred by a bacterial infection against cancer: study of an invertebrate model.

All multicellular organisms are exposed to a diversity of infectious agents and to the emergence and proliferation of malignant cells. The protection conferred by some infections against cancer has been recently linked to the production of acquired immunity effectors such as antibodies. However, the evolution of innate immunity as a mechanism to prevent cancer and how it is jeopardized by infections remain poorly investigated. Here, we explored this question by performing experimental infections in two genetically modified invertebrate models (Drosophila melanogaster) that develop invasive or non-invasive neoplastic brain tumors. After quantifying tumor size and antimicrobial peptide gene expression, we found that Drosophila larvae infected with a naturally occurring bacterium had smaller tumors compared to controls and to fungus-infected larvae. This was associated with the upregulation of genes encoding two antimicrobial peptides-diptericin and drosomycin-that are known to be important mediators of tumor cell death. We further confirmed that tumor regression upon infection was associated with an increase in tumor cell death. Thus, our study suggests that infection could have a protective role through the production of antimicrobial peptides that increase tumor cell death. Finally, our study highlights the need to understand the role of innate immune effectors in the complex interactions between infections and cancer cell communities in order to develop innovative cancer treatment strategies.

Human Plasmodium vivax diversity, population structure and evolutionary origin.

More than 200 million malaria clinical cases are reported each year due to Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been neglected and understudied for a long time, due to its lower mortality in comparison with Plasmodium falciparum. A renewed interest has emerged in the past decade with the discovery of antimalarial drug resistance and of severe and even fatal human cases. Nonetheless, today there are still significant gaps in our understanding of the population genetics and evolutionary history of P. vivax, particularly because of a lack of genetic data from Africa. To address these gaps, we genotyped 14 microsatellite loci in 834 samples obtained from 28 locations in 20 countries from around the world. We discuss the worldwide population genetic structure and diversity and the evolutionary origin of P. vivax in the world and its introduction into the Americas. This study demonstrates the importance of conducting genome-wide analyses of P. vivax in order to unravel its complex evolutionary history.

The evolution of resistance and tolerance as cancer defences.

Although there is a plethora of cancer associated-factors that can ultimately culminate in death (cachexia, organ impairment, metastases, opportunistic infections, etc.), the focal element of every terminal malignancy is the failure of our natural defences to control unlimited cell proliferation. The reasons why our defences apparently lack efficiency is a complex question, potentially indicating that, under Darwinian terms, solutions other than preventing cancer progression are also important contributors. In analogy with host-parasite systems, we propose to call this latter option 'tolerance' to cancer. Here, we argue that the ubiquity of oncogenic processes among metazoans is at least partially attributable to both the limitations of resistance mechanisms and to the evolution of tolerance to cancer. Deciphering the ecological contexts of alternative responses to the cancer burden is not a semantic question, but rather a focal point in understanding the evolutionary ecology of host-tumour relationships, the evolution of our defences, as well as why and when certain cancers are likely to be detrimental for survival.

Can postfertile life stages evolve as an anticancer mechanism?

Why a postfertile stage has evolved in females of some species has puzzled evolutionary biologists for over 50 years. We propose that existing adaptive explanations have underestimated in their formulation an important parameter operating both at the specific and the individual levels: the balance between cancer risks and cancer defenses. During their life, most multicellular organisms naturally accumulate oncogenic processes in their body. In parallel, reproduction, notably the pregnancy process in mammals, exacerbates the progression of existing tumors in females. When, for various ecological or evolutionary reasons, anticancer defenses are too weak, given cancer risk, older females could not pursue their reproduction without triggering fatal metastatic cancers, nor even maintain a normal reproductive physiology if the latter also promotes the growth of existing oncogenic processes, e.g., hormone-dependent malignancies. At least until stronger anticancer defenses are selected for in these species, females could achieve higher inclusive fitness by ceasing their reproduction and/or going through menopause (assuming that these traits are easier to select than anticancer defenses), thereby limiting the risk of premature death due to metastatic cancers. Because relatively few species experience such an evolutionary mismatch between anticancer defenses and cancer risks, the evolution of prolonged life after reproduction could also be a rare, potentially transient, anticancer adaptation in the animal kingdom.

Second-harmonic-generation enhancement in cavity resonator integrated grating filters.

We demonstrate numerically and experimentally second-harmonic generation (SHG) in a cavity resonator integrated grating filter (CRIGF, a planar cavity resonator made of Bragg grating reflectors) around 1550 nm. SHG is modeled numerically for several different systems, including a thin plane layer of LiNbO3 without and with a grating coupler to excite a waveguide mode. We demonstrate that when the waveguide mode is confined to a CRIGF, designed to work with focused incident beams, the SHG power is increased more than 30 times, compared to the case of a single grating coupler used with an almost collimated pump beam.

Differences in mutational processes and intra-tumour heterogeneity between organs: The local selective filter hypothesis.

Extensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumours, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment. We argue that these phenomena are, at least partially, explainable by the evolutionary ecology of organs' theory, in the same way that environmental adversity shapes mutation rates and level of polymorphism in organisms. Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at suppressing tumours. When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences. In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis. Lay summary: Different levels of mutations and intra-tumour heterogeneity have been observed between cancer types and organs. Anti-cancer defences are unequal between our organs. We propose that mostly aggressive neoplasms (i.e. higher mutational and ITH levels), succeed in emerging and developing in organs with strong defences.

Rodent malaria in Gabon: Diversity and host range.

Malaria parasites infect a wide range of vertebrate hosts, such as reptiles, birds and mammals (i.e., primates, ungulates, bats, and rodents). Four Plasmodium species and their subspecies infect African Muridae. Since their discoveries in the 1940s, these rodent Plasmodium species have served as biological models to explore many aspects of the biology of malaria agents and their interactions with their hosts. Despite that, surprisingly, little is known about their ecology, natural history and evolution. Most field studies on these parasites, performed from the 1940s to the early 1980s, showed that all rodent Plasmodium species infect only one main host species, the thicket rat. In the present study, we re-explored the diversity of Plasmodium parasites infecting rodent species living in peridomestic habitats in Gabon, Central Africa. Using molecular approaches, we found that at least two Plasmodium species (Plasmodium vinckei and Plasmodium yoelii) circulated among five rodent species (including the invasive species Mus musculus). This suggests that the host range of these parasites might be larger than previously considered. Our results also showed that the diversity of these parasites could be higher than currently recognized, with the discovery of a new phylogenetic lineage that could represent a new species of rodent Plasmodium.

Transmissible cancer and the evolution of sex.

The origin and subsequent maintenance of sex and recombination are among the most elusive and controversial problems in evolutionary biology. Here, we propose a novel hypothesis, suggesting that sexual reproduction not only evolved to reduce the negative effects of the accumulation of deleterious mutations and processes associated with pathogen and/or parasite resistance but also to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells. Sexual reproduction permits systematic change of the multicellular organism's genotype and hence an enhanced detection of transmissible cancer cells by immune system. Given the omnipresence of oncogenic processes in multicellular organisms, together with the fact that transmissible cancer cells can have dramatic effects on their host fitness, our scenario suggests that the benefits of sex and concomitant recombination will be large and permanent, explaining why sexual reproduction is, despite its costs, the dominant mode of reproduction among eukaryotes.

Recent Adaptive Acquisition by African Rainforest Hunter-Gatherers of the Late Pleistocene Sickle-Cell Mutation Suggests Past Differences in Malaria Exposure.

The hemoglobin ßS sickle mutation is a textbook case in which natural selection maintains a deleterious mutation at high frequency in the human population. Homozygous individuals for this mutation develop sickle-cell disease, whereas heterozygotes benefit from higher protection against severe malaria. Because the overdominant ßS allele should be purged almost immediately from the population in the absence of malaria, the study of the evolutionary history of this iconic mutation can provide important information about the history of human exposure to malaria. Here, we sought to increase our understanding of the origins and time depth of the ßS mutation in populations with different lifestyles and ecologies, and we analyzed the diversity of HBB in 479 individuals from 13 populations of African farmers and rainforest hunter-gatherers. Using an approximate Bayesian computation method, we estimated the age of the ßS allele while explicitly accounting for population subdivision, past demography, and balancing selection. When the effects of balancing selection are taken into account, our analyses indicate a single emergence of ßS in the ancestors of present-day agriculturalist populations ∼22,000 years ago. Furthermore, we show that rainforest hunter-gatherers have more recently acquired the ßS mutation from the ancestors of agriculturalists through adaptive gene flow during the last ∼6,000 years. Together, our results provide evidence for a more ancient exposure to malarial pressures among the ancestors of agriculturalists than previously appreciated, and they suggest that rainforest hunter-gatherers have been increasingly exposed to malaria during the last millennia.

Extensive diversity of malaria parasites circulating in Central African bats and monkeys.

The order Haemosporidia gathers many protozoan parasites which are known to infect many host species and groups. Until recently, the studies on haemosporidian parasites primarily focused on the genus Plasmodium among a wide range of hosts. Genera, like the genus Hepatocystis, have received far less attention. In the present study, we present results of a survey of the diversity of Hepatocystis infecting bats and monkeys living in a same area in Gabon (Central Africa). Phylogenetic analyses revealed a large diversity of Hepatocystis lineages circulating among bats and monkeys, among which certain were previously observed in other African areas. Both groups of hosts harbor parasites belonging to distinct genetic clades and no transfers of parasites were observed between bats and monkeys. Finally, within each host group, no host specificity or geographical clustering was observed for the bat or the primate Hepatocystis lineages.

Is adaptive therapy natural?

Research suggests that progression-free survival can be prolonged by integrating evolutionary principles into clinical cancer treatment protocols. The goal is to prevent or slow the proliferation of resistant malignant cell populations. The logic behind this therapy relies on ecological and evolutionary processes. These same processes would be available to natural selection in decreasing the probability of an organism's death due to cancer. We propose that organisms' anticancer adaptions include not only ones for preventing cancer but also ones for directing and retarding the evolution of life-threatening cancer cells. We term this last strategy natural adaptive therapy (NAT). The body's NAT might include a lower than otherwise possible immune response. A restrained immune response might forego maximum short-term kill rates. Restraint would forestall immune-resistant cancer cells and produce long-term durable control of the cancer population. Here, we define, develop, and explore the possibility of NAT. The discovery of NAT mechanisms could identify new strategies in tumor prevention and treatments. Furthermore, we discuss the potential risks of immunotherapies that force the immune system to ramp up the short-term kill rates of malignant cancer cells in a manner that undermines the body's NAT and accelerates the evolution of immune resistance.

Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution.

Although Plasmodium vivax is responsible for the majority of malaria infections outside Africa, little is known about its evolution and pathway to humans. Its closest genetic relative, P. vivax-like, was discovered in African great apes and is hypothesized to have given rise to P. vivax in humans. To unravel the evolutionary history and adaptation of P. vivax to different host environments, we generated using long- and short-read sequence technologies 2 new P. vivax-like reference genomes and 9 additional P. vivax-like genotypes. Analyses show that the genomes of P. vivax and P. vivax-like are highly similar and colinear within the core regions. Phylogenetic analyses clearly show that P. vivax-like parasites form a genetically distinct clade from P. vivax. Concerning the relative divergence dating, we show that the evolution of P. vivax in humans did not occur at the same time as the other agents of human malaria, thus suggesting that the transfer of Plasmodium parasites to humans happened several times independently over the history of the Homo genus. We further identify several key genes that exhibit signatures of positive selection exclusively in the human P. vivax parasites. Two of these genes have been identified to also be under positive selection in the other main human malaria agent, P. falciparum, thus suggesting their key role in the evolution of the ability of these parasites to infect humans or their anthropophilic vectors. Finally, we demonstrate that some gene families important for red blood cell (RBC) invasion (a key step of the life cycle of these parasites) have undergone lineage-specific evolution in the human parasite (e.g., reticulocyte-binding proteins [RBPs]).