Transcriptomic landscape of host-pathogen-antibiotic interactions in Drosophila melanogaster model infected with Gram-negative ESKAPE bacteria
Project Director: Prof. univ. dr. Mariana Carmen Chifiriuc
Project code: PN-III-P4-PCE-2021-1797
Contract number: PCE 96
Project title: Transcriptomic landscape of host-pathogen-antibiotic interactions in Drosophila melanogaster model infected with Gram-negative ESKAPE bacteria
Project Acronym: TRANSCEND
Project Duration: 31 months
The total buget of the project: 1.200.000,00
The starting date of the contract: 22/06/2022
The date of conclusion of the contract: 31/12/2024
Abstract
While the antimicrobial resistance crisis continues to grow and spread and the discovery of new antibiotics is slow, it is acutely important to improve current antibiotics use. The in vitro assays of antibiotic susceptibility have a low predictability on the antibiotics efficiency in treating multi-resistant bacterial infections, overlooking the complexity of interactions occurring in vivo. To surpass these limitations, we will use for the first time the powerful Drosophila melanogaster model to evaluate the effects of ESKAPE pathogens and antibiotics on D. melanogaster and its microbiota. In this purpose, D. melanogaster males will be infected with Gram-negative ESKAPE bacteria and treated with colistin and carbapenems. Then, state-of-the art methodology (molecular biology, omics and genetic methods, as well as biostatistics and bioinformatic approaches) will be applied. The in vitro and in vivo antibiotic resistance genes expression profiles and the eukaryotic genes expression profiles expected to be triggered by infection and antibiotic treatment will be assessed. This approach will allow us to unveil some of the key determinants of bacterial resistance expression and of D. melanogaster genome and microbiome functional modulation by infection and treatments and antibiotic efficacy in vivo. Hence, advances in our ability to predict efficacy of last resort antibiotics for curbing difficult infections are reasonably expected.
Project Objective
The main purpose of this project is to evaluate and understand how the specific eukaryotic and prokaryotic gene expression profiles are interactively modulated during infection and antibiotic treatments. For this endeavour, we will focus on the following actors: i) D. melanogaster model; ii) highly resistant Gram-negative pathogens from the ESKAPE group, respectively XDR K. pneumoniae, P. aeruginosa and A. baumannii strains, belonging to clinically and epidemiologically important clones circulating in Romanian hospitals and released in the aquatic environment and iii) two last resort antibiotics, i.e. colistin (as a model of potentially antagonistic effects on the antibiotic efficiency exhibited by the host environment) and one carbapenem (as a model for synergic effect of bactericidal antibiotics and the host antimicrobial peptides).
Expected results
The used of a standardized, affordable in vivo model, will allow us to get insights in the complex host-pathogen and inter-microbial interactions in the infection environment and to improve our understanding regarding the factors contributing to the in vivo efficiency of antibiotics. The synthetic analysis of the results will allow us to reveal the host influence on the expression of ESKAPE resistance genes in vivo, as well as the modulation of fly genome and microbiome during infection with highly resistant pathogens and treatments with last resort antibiotics.
Project team (alphabetically):
Barbu Ilda
Chifiriuc Mariana Carmen – project director
Constantin Nicoleta Denisa
Ecovoiu Alexandru
Gheorghe Irina
Grădișteanu Grațiela
Ionașcu Adrian
Măruțescu Luminița
Popa Marcela
Rațiu Attila Cristian
