Functional characterization of Neisserial toxin-antitoxin systems

Toxin-antitoxin (TA) systems are commonly found in both Gram-positive and Gram-negative bacteria and comprise a stable toxin able to stall bacterial replication and an antitoxin that neutralises the activity of the toxin. When under stress conditions, such as nutrient limitation, temperature shock, contact with host cells or exposure to antimicrobials, the antitoxins are degraded leaving the toxin free to arrest bacterial growth. This viable, but non-growing, ‘persister’ state facilitates bacterial survival during stress and increases 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 meningitidis (meningococcus) and Neisseria gonorrhoeae (gonococcus). N. meningitidis is an upper respiratory tract commensal, capable of causing outbreaks of invasive disease, including meningitis and septicaemia, whilst N. gonorrhoeae is the causative agent of the sexually-transmitted infection gonorrhoea. This project will investigate the role that TA systems play in these organism’s ability to survive and persist in the host; it will provide training in molecular microbiology, protein biochemistry and tissue culture.

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