Project description

Tuesday - 22/12/2015 02:54

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.

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