You are here : Home > BCI Laboratory > Study of the regulation of type III and type IV secretion systems in Pseudomonas aeruginosa: Approaches of chemogenomics, random mutagenesis and study of a clinical isolate

Khady Haby Sall

Study of the regulation of type III and type IV secretion systems in Pseudomonas aeruginosa: Approaches of chemogenomics, random mutagenesis and study of a clinical isolate

Published on 28 November 2013


Thesis presented November 28, 2013

Abstract :
Pseudomonas aeruginosa is a gram negative bacillum present in several places. This opportunistic pathogen has the capacity to infect a wide range of hosts: plants, animals, humans. This bacterium, that shows an impressive adaptability relying on a multifactorial virulence, possesses two lifestyles. These lifestyles are associated with specific virulence​ patterns of expression. Under its planktonic form, P. aeruginosa can provoke acute infections thanks to the activation of T2 and T3SS or induces chronic infections in cystic fibrosis patients’ lungs where it establishes a biofilm (community life). The expression of virulence factors is linked to the integration of several environmental cues that are transduced through two-component systems and secondary messengers like c-di-GMP and that lead to a fine tuned regulation. The nature and the mechanisms involved in this signal transduction remain largely unknown. The goal of this thesis was to decipher molecular mechanisms of signal detection and transduction that govern the adaptive pathogen response to host environment using the combination of a chemogenomics, random mutagenesis and study of clinical isolate. During this work, we screened two commercial libraries and set up a robust high throughput screening test to analyze huge molecules libraries. By setting up a double reporter-gene strain, we realized a transposon mutagenesis bank and identified interesting candidates with a down-regulated T3SS. Finally, the study of the particular clinical isolate CHA (from a cystic fibrosis patient), leads to the discovery that a deletion in the gene encoding for the important regulator GacS shapes the aggressive phenotype of this strain.


Keywords:
Pseusdomonas aeruginosa, regulation, High throughput screening, cystic fibrosis, T3SS, ​T6SS-1

Download this thesis.