A genetically modified nasopharyngeal commensal as a platform for human bacteriotherapy

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Our long term objective is to invent a new type of medicine which consists of living bacteria which would be given as nose drops (akin to the Yacult drink that is commercially available and taken by mouth by people with bowel problems). We have recently published work in which we inoculated a small dose of a `friendly bacterium` - Neisseria lactamica - into the noses of participants and found that the bacterium was still present in their throats 6 months later, and caused no ill effects. Furthermore, the friendly bacterium stopped the paticipants from being infected with a related bacterium which can cause meningitis. This concept of `bacteriotherapy` is rapidly gaining credence as a way to treat bacterial infections - for example we now treat Clostridium difficile diarrhoea with bacteria derived from the stools of donors, and it works very well. We have discovered a way to genetically transform Neisseria lactamica with genes from a very wide range of living things, which means that we could potentially develop a range of bacterial medicines containing genes which exert specific desired effects in the recipients. For example, we could make a bacterial medicine which makes substances which kill harmful bacteria or viruses or which simply out-competes them. One of the problems with our idea is that when we inoculated students with the Neisseria lactamica, we found that 65% of them became colonised, but this was only 35% if we restricted the study to non-smokers. This would not be a very reliable bacteriotherapy and we would need to increase the likelihood of colonisation if this approach is to be of any use. So, in the proposed study, we will use our technology to make a strain of Neisseria lactamica which makes two proteins that are normally used by other bacteria to stick to cells. We will use for this purpose two proteins that are normally made by the related meningitis bacterium Neisseria meningitidis, to stick to stick to the inner surface of the nose when it colonises humans. We will show that the new genetically modified strain has all of the characteristics we expect including the ability to stick better to cells in the laboratory, and that is safe to release into the community (because it is not more resistant to the immune system, or to antibiotics, and does not have increased capacity to gradually change into something more dangerous). We will then apply to the appropriate regulators for permission to repeat our studies with human volunteers to see if the genetically modified strain that we have generated manages to colonise better than the wild type bacterium from which it is derived. This would be the subject of a follow-on study - if that were to be successful this strategy that we have devised would be a future therapy of relevance to any disease process involving colonisation of the nasopharynx, eg pneumonia, Chronic Bronchitis, sinusitis, ear infection, meningitis or MRSA colonisation and disease.