Antimicrobial resistance​
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Antimicrobial resistance (AMR) occurs naturally in bacteria and other microorganisms, but increases when antimicrobials (antibiotics, antivirals, antifungals) are used. AMR accounts for an estimated 700,000 deaths per year and has been classified by WHO as one of the ten threats to global health in 2019. Although AMR is most clinically relevant in pathogenic bacteria, antimicrobial resistance genes exist in both pathogenic and non-pathogenic bacteria, and large reservoirs of these genes exist in all ecosystems, including in commensals at all sites of the human or animal body. There is a rising concern about how much of these resistance genes can be transferred from the gut microbiota reservoir to a pathogenic bacteria infecting a human or animal.
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My project conducted at the Geelong Centre for Emerging Infectious Diseases (Geelong, Australia) focused on characterizing the antibiotic resistome of 'healthy' humans and animals collected in Australia, by investigating the diversity and abundance of antimicrobial resistance genes in the fecal microbiota. We assessed and compared the performance of available tools for the analysis of bacterial resistomes by the use of non-targeted shotgun metagenomics sequencing (analyzed in-house or using web-based tools) and targeted sequencing (using commercially available panels).
The aim of my latest project conducted at USDA (Ames, IA - Food Safety and Enteric Pathogens Research Unit) is to understand the mechanisms underlying the transfer of resistance genes between bacteria. I am especially focusing on horizontal gene transfer through natural transformation within and between Campylobacter species in turkeys, and between Salmonella and other commensal bacteria in chikens. In order to assess how often those natural transfers occur in a controlled environment, I realized in vitro co-culture experiments with wild strains carrying different resistance genes, after which phenotypic and genotypic resistances were assessed. Using pairs of strains showing a successful HGT event between Campylobacter strains, the next step was to conduct an experimental co-infection in turkeys to assess if this could be reproduced in Campylobacter natural environment, i.e. within the gut of an animal host. The other animal experiment aimed to assess the possible acquisition of resistance genes from commensal bacteria colonizing the eggshells of chicks to (experimentally inoculated) Salmonella in the gut. This work is conducted with Dr Looft (USDA) and in collaboration with Dr Kathariou (NC State University).
Presentation given as an invited speaker for 'World One Health Day' during Barwon Health / Deakin University Research Week, November 2018, Geelong, Australia.
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Fieldwork (rat trapping) in Mahe island in Seychelles in 2013 with an amazing team: from left to right Erwan Lagadec, Gildas LeMinter and Julien Mélade
Albino wild rat trapped during fieldwork in Mahe island in Seychelles in 2013.
Leptospirosis diversity in the tropics
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Leptospirosis is a zoonotic bacterial disease of global importance caused by leptospires, bacteria belonging to the order Spirochaetales. The clinical spectrum of human infections ranges from mild flu-like illness to severe or even fatal outcome. A large spectrum of animal hosts, including rodents (considered as the main reservoir), domestic mammals (including livestock) and wildlife, are reservoirs for leptospires and can carry the infection and contribute to the burden of human disease. Leptospires are maintained in the proximal tubules of the kidneys of infected animals (chronically in animal reservoirs, or temporarily during acute infection) and excreted in urine, from which they contaminate soil, surface water, streams and rivers. Environmental sources of human contamination point to the importance of an hydrotelluric reservoir. Humans are infected through direct contact with urine or tissues from infected animals, or indirectly via a contaminated environment, particularly if there are abrasion or cuts in the skin.
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Specific serovars are more commonly associated with particular reservoir hosts, such as Ballum with mice, Canicola with dogs, or Icterohaemorrhagiae with rats. But in many countries, serology is not routine practice. Also, if rats are often believed to be the main reservoir of leptospires, there is a huge heterogeneity of animal reservoirs between countries, but also within a same country (between urban and rural areas for example).
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The common aim of my previous studies, conducted on tropical islands including Reunion Island, Seychelles, Comoros and Tahiti, was to identify the Leptospira genotypes circulating in humans and animals to compare them. The identification of animal carriers and reservoirs of pathogenic leptospires is key to understanding the most probable routes of human exposure, and to recommend public health interventions to reduce leptospirosis disease burden. My ongoing work is focusing on exploring the diversity of Leptospira in rats and bats in Papua New Guinea, as well as in rodents in Cambodia. This work is conducted in collaboration with Paul Horwood (JCU, Townsville, Australia) and researchers from Pasteur Institute Cambodia.
Melioidosis in the French West Indies and in South East Asia, and environmental surveillance
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Melioidosis is a zoonotic bacterial disease caused by the saprophytic bacterium Burkholderia pseudomallei. A recent spatial modeling study estimated that there are about 165,000 human melioidosis cases per year worldwide, of which 89,000 (54%) end in death. Globally, mortality due to melioidosis (89,000 per year) is comparable to measles, and higher than that for leptospirosis and dengue infections. Nonetheless, melioidosis is so neglected that it is missing from the lists of neglected tropical diseases (NTDs).
Melioidosis predominantly affects people in regular contact with soil and water. However, the spatial distribution of the disease is highly heterogeneous, which is believed to be correlated with a highly restricted ecological niche of the bacteria in the environment. However, in many countries, information about the organism’s ecology is limited, which makes it complicated to identify the bacteria most suitable environment. B. pseudomallei seems to prefer moist clay soils and associated fresh water. It is clear that individuals with a close association with the environment in regions where the organism is endemic are at risk of acquiring the disease.
Also, animals exposure to the bacteria is rarely investigated, even though many species can be contaminated, and sometimes get sick.
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My projects on melioidosis seek to investigate, through a One Health approach, the local eco-epidemiology of the disease. Considering the spatial heterogeneity of the environmental occurrence of the bacteria, the objective is to identify / assess the ecological niche of B. pseudomallei and correlate this information with the distribution of human cases / seropositive animals in order to identify high-risk areas, and to help implementing an active surveillance system.
Mégane Gasqué, a PhD student at IRD (iEES-Paris, team CoMic) and ANSES (Laboratory for Animal Health), is conducting a study in the French West Indies and French Guyana, where sporadic cases (in Guadeloupe and Martinique) or no human cases have been identified. She is collecting both animal and environmental samples to detect the bacteria, and assess where the bacteria is present in the environment.
Mégane is supervised by Karine Laroucau (ANSES), Emma Rochelle Newall (IRD) and myself.
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The morphology of colonies of Burkholderia pseudomallei may be smooth and mucoid or, more distinctively, dry and wrinkled after incubation for a few days.
