Functional characterization of gonococcal toxin-antitoxin systems

About the Project

Toxin-antitoxin (TA) systems are commonly found in bacteria and comprise a stable toxin able to stall bacterial replication and an antitoxin that neutralises the activity of the toxin. Under specific conditions, the ratio of toxin: antitoxin shifts, leaving non-sequestered toxin available to arrest bacterial growth. This viable, but non-growing, ‘persister’ state may facilitate bacterial survival during stress and increase tolerance to antibiotics. It follows that manipulating bacterial TA systems, which are not found in eukaryotic cells, may result in novel therapeutic interventions to interrupt colonisation, persistence or pathogenesis.

We have identified several putative TA loci in available genome sequences of Neisseria gonorrhoeae (gonococcus). N. gonorrhoeae is a worldwide sexually-transmitted bacterial pathogen. Asymptomatic gonococcal infections represent an important reservoir for the continued transmission of the disease. Of concern, there is no licenced vaccine available to prevent gonococcal infection. Furthermore, antibiotic resistance has also increased in N. gonorrhoeae. Overall, there is an urgent need to develop a better understanding of gonococcal infections and novel antibiotics and treatment strategies to combat the disease.

This project will investigate the role that TA systems play in the ability of the gonococcus to survive and persist in the host; it will provide training in molecular microbiology, protein biochemistry and tissue culture.

References

1. Lobato-Marquez D, Diaz-Orejas R, Garcia-Del Portillo F. Toxin-antitoxins and bacterial virulence. FEMS Microbiol Rev. 2016 Sep;40:592-609.
2. Unemo M et al. Gonorrhoea. Nature Rev Dis Primers. 2019 5:79.