Authors: Hannah Makin, Future Science Group
A recent study published in Antimicrobial Agents and Chemotherapy has identified a potential new treatment for gonorrhoea. The novel therapy targets and inhibits one of the enzymes needed for Neisseria gonorrhoeae to respire in anaerobic conditions, which ultimately leads to the death of this infection-causing bacterium.
The ‘superbug’ status of this bacterium has prompted new research into developing novel treatment strategies for this highly prevalent disease. Researcher at the Oregon State University (OR, USA), Aleksandra Sikora, stated: “The infections very often are silent. Up to 50% of infected women don’t have symptoms, but those asymptomatic cases can still lead to some very severe consequences for the patient’s reproductive health, miscarriage or premature delivery.”
In this study the team, led by Sikora, investigated the effects of targeting nitrite reductase AniA. This enzyme is required for N. gonorrhoeae to respire anaerobically and form biofilms in the genitourinary tract.
It was demonstrated that altering specific catalytic residues in this enzyme inhibited its nitrate reductase activity, meaning that the bacterium is therefore unable to respire in its oxygen-poor biofilm environment.
Sikora commented on the uniqueness of this potential targeting strategy: “Bacteria in biofilms display increased resistance to antimicrobials. The enzyme is only necessary for cell viability when these bacteria grow under anaerobic conditions, including when they grow in the biofilm. Most antibiotics target essential cell functions; this one doesn’t. It’s only at a certain stage of growth that the bacteria are affected, which means the development of resistance won’t be as fast.”
“Imagine this research approach as having a pond with a lot of fish, and you’re using the protein as the bait. The peptides bind with the protein, and you go through multiple rounds to identify the peptides that have the strongest binding ability. You start with a billion peptides and end up with one that strongly inhibits the enzyme and ultimately kills the bacteria.”
Twenty-nine unique peptides, including one termed C7-3, were identified in biopanning experiments as being able to bind to this AniA enzyme. Further ELISA and computational docking studies revealed C7-3 to be the most potent inhibitor of AniA.
Although further studies are required, this research presents a promising therapeutic targeting strategy that could be utilized for anti-gonococcal drug development.
Sources: Sikora AE, Mills RH, Weber JV et al. Peptide inhibitors targeting the Neisseria gonorrhoeae pivotal anaerobic respiration factor AniA. Antimicrob. Agents Chemother. doi: 10.1128/AAC.00186-17 (2017) (Epub ahead of print); http://oregonstate.edu/ua/ncs/archives/2017/jun/new-gonorrhea-treatment-targets-enzyme-needed-respiration