Pseudomonas virulence unveiled
P. aeruginosa is inherently multi-drug resistant which hampers treatment efficacy of antibiotics and other antimicrobial agents. This resistance has been attributed to the bacterial membrane which carries specialised efflux pumps, rendering it impermeable to most drugs. Clinical isolates of P. aeruginosa have been found to express high levels of such efflux systems (MexEF-OprN), which also facilitate bacterial colonisation and spread within the host. Understanding how these pumps regulate key bacterial properties was the subject of the EU-funded 'Dissecting the role of a novel transcriptional regulator in microbial-host interactomes.' (MEXT REGULATION) project. The MexEF-OprN efflux system is transcriptionally regulated by MexT. Scientists therefore concentrated their efforts on delineating the role of this protein in bacteria survival and spread. They obtained bacteria overexpressing MexT and identified the MexT-regulated gene, PA4353, as a key determinant of biofilm formation and growth. Interestingly, MexT seemed to additionally impact the virulence of P. aeruginosa in the wax moth model. Overexpression of this master regulator significantly reduced the levels of P. aeruginosa required to kill the wax moth. Overall, the work by the MEXT REGULATION study established MexT as an important factor of P. aeruginosa virulence. P. aeruginosa is the predominant cause of morbidity in cystic fibrosis patients. Elimination of MexT from the pathogen could reduce its virulence and therefore provide a therapeutic target.
Keywords
Pseudomonas aeruginosa, cystic fibrosis, antibiotic resistance, efflux systems, MexT, protein
