Furthermore several infectious agents become more and more resistant to the available biocides (antibiotics, antifungal agents, antiparasitic agents…), thus presenting multi-drug resistance (MDR) phenotypes, which are mainly explained by the over expression of MDR efflux pumps.
It is now admitted that, although the intensive use of drugs in human, veterinary, agricultural practices contributes to the development of resistance traits among microorganisms. For instance, the use of antibiotics do exist in other contexts different from the therapeutical practices (animal production, horticulture, irrigation with waste water, organic amendments,…).
In addition, other selective pressures co-select for resistance to antibiotics (metals, hydrocarbons, other biocides). Anthropization thus largely contributes to the emergence and transmission of resistance genes in the environment, and highly contaminated soils and waters could be seen as hot spots for the expression of MDR phenotypes. We will focus on two categories of organisms.
First, plants growing in these environments are exposed to resistant microorganisms and as they share close relationships together, especially in the rhizosphere, plants may have developed specific strategies to inhibit or cope with these mechanisms and could then represent a reservoir of bioactive compounds that could be used as anti-infectious agents.
Second, mosquito vectors that have aquatic larvae stage evolving in these polluted areas may generate resistance link to the mosquito genome expression per se but also through the associated microorganisms that may contribute to detoxification processes. In this context, the general objective of the project is to survey microorganisms in highly anthropized environments with the aim to discover potential pathogens and their drug resistance mechanisms, and prevent or alert associated disease emerging risks as well as to propose possible control strategies. To achieve this purpose, three specific objectives were defined:
1) To draw a map of identified areas of importance regarding the emergence risks through the human practices (organic and pesticide amendments, heavy metal extraction, antibiotic-treated cattle…) and to make an inventory of environmental resistant pathogens and resistance mechanisms.
2) To investigate plant compounds specifically expressed in these environments, as well as their associated rhizospheric microbes and HTS of compounds active against MDR pathogens and/or able to inhibit resistance mechanisms.
3) To explore the breeding sites for larvae of mosquitoes in polluted water close to plants to isolate mosquito associated microbiota (pathogens and symbionts) that may be contributing to highly mosquito adaptive process as well as to decipher the genetic determinants involved.
This integrated approach is rare and interesting as it is based on existing expertise through collaborations with the VAST and GDRI “Biodiversity and Infectious Disease”. Based on existing collaborations, Vietnamese contaminated sites have been identified and plants leaving there selected. These areas hosted a huge number of mosquitoes, particularly Aedes aegypti involved in Dengue fever transmission. This project will benefit both public health and for training of new Vietnamese USTH researchers, and aims to build a research laboratory viable in the long-term for them.