Recent research at York University (Ward & Lynam (W&L)), UK, suggests the possible efficacity of carbon monoxide-releasing molecules as an antimicrobial against gonorrhoea. The work is at an early stage – but the urgency of our current situation lends it a heightened interest.
Growing resistance of Neisseria gonorrhoeae (Ng) to the last-defence antibiotic treatments (Lewis/STIs) – cephixime and ceftriaxone – has placed sexual health policy in a dilemma: to have an impact on the epidemic requires them to focus treatment on core-groups; yet the treatment of these individuals has to be shown to heighten antibiotic resistance (Chan & Fisman/STIs). Ison & Unemo/STIs survey the narrowing options, including heightened surveillance (see also Unemo & Khotenashvili/STIs) and the careful stewarding of our remaining antibiotic resources. Others suggest recourse to less obvious measures, such as the comprehensive treatment of pharyngeal Ng in MSM (Lewis/STIs), or the use of topical antiseptics (Miari & Ison/STIs). Ultimately, however, the answer will lie in the developments of new antibiotics.
So how about the York researchers’ carbon monoxide-releasing molecules (CORMs)? Though – to repeat – it is early days, this avenue looks promising. The agent, tryptophan manganese carbonyl (Trypto-CORM), has been shown by earlier studies to be toxic to Escherichia coli and Staphylococcus aureus through the effect of CO molecules released by Trypto-CORM when irradiated. W&L report that in the case of Ng, the bacterium appeared to be destroyed even by the very small amounts of CO released before irradiation. The idea that Ng might be ‘exquisitely sensitive’ to CO would, of course, be good news. It suggests the levels of CO necessary for efficacity against Ng might be sufficiently low to eliminate undesired toxic effects. However, the results of W&L also raise the suspicion that in the case of Ng, the cytotoxic effect might arise from some mechanism other than release of CO. Fortunately, another innovation of the study appears to eliminate that possibility. This is the use of extremely high CO affinity leg-haemoglobin (as opposed to the less high affinity deoxy-myoglobin) to ‘rescue’ the Ng culture by ‘scavenging’ the CO. So it really does seem that the sensitivity of Ng to CO, not some other mechanism, is producing the cytotoxic effect.
A final potentially medically significant element of the study is the effect of culture age. Cultures that had been stored for are longer time were more sensitive to Trypto-CORM – a finding that turns out not to be attributable to the number of viable cells in the inoculums. The authors suggest the effect is due to the depletion in the number of active haem-copper oxidase complexes in near dormant cells. This too could be good news. Persistent bacteria in an infection that are recalcitrant to treatment are frequently slow-growing or dormant, and could be particularly susceptible to Trypto-CORM.