SELECTAR - Selection for antimicrobial resistance by antimicrobial production waste

Antibiotics are one of the most crucial medicines on the planet. Without them we are unable to treat the vast majority of infectious diseases, ranging from life threatening intestinal infections and blood stream infections, to treating debilitating chronic infections such as urinary tract infections and respiratory infections. Antibiotics are required to prevent the deaths of patients suffering from respiratory diseases such as CF and COPD, and are the corner stone of treatments for diseases such as cancer and leukaemia where it is necessary to prevent infections during treatment.

The majority of the worlds antibiotics are produced in pharmaceutical factories in India. Antibiotics can be produced by chemical synthesis or by growing vast number of the microorganisms which naturally produce them. Either method results in the production of large quantities of waste, potentially containing active antibiotics and/or chemicals which may be toxic to bacteria and other cell types. This waste goes through treatment plants before being released into the environment. This creates an enormous potential issue, as the more we expose bacteria to antibiotics the faster they evolve resistance to the drugs meaning they cant be used to treat infections. There is also the possibility that release of waste into the environment kills all bacteria except those resistant, decimating important bacterial ecosystems and increasing resistant bacteria.

We desperately need to know exactly how much the release of antibiotic production waste leads to the feared end results mentioned above . To do this we will sample environments into which antibiotic production waste is released, and compare them to pristine environments. This will allow us to determine exactly what effect the waste has on the microbial ecosystem, does it kill all beneficial bacteria to only leave harmful resistant bacteria alive. We will carefully examine the waste to determine exactly how much active antibiotic is released but also which other potentially toxic chemicals are contained within the waste that may affect bacteria. And we will then test the ability of these chemicals to also induce resistant bacteria, as a consequence of them trying to avoid chemical killing.

The proposed research project could have immediate and real impact across a number of stakeholders and disciplines

Pharmaceutical industry: Through our Indian collaborators we will release our entire data sets when publication ready to the companies whose sites we are studying, and leveraging those companies, to the wider Indian pharmaceutical industry. Full quantifiable data on the impact of waste release on microbial ecosystems, the extent to which this selects for resistance, and a full determination of all chemical components which can select for resistance and at which concentrations, will allow pharma to develop research-informed guidelines on safe discharge levels as well as a full list of chemicals of concern to focus environmental monitoring upon. This data will be transformative to the Indian antimicrobial production industry. Through conference presentations we will also ensure our data is presented to relevant pharmaceutical stakeholders in Europe. We will also work with the PIs of the other funded UK-India projects to ensure our data is distributed across the wider community.

General public: Currently there is no empirical evidence to inform if the release of waste into the environment represents a public health risk. Our microbiological data will be the most comprehensive analysis available of how waste release affects the microbial ecosystem, and if release leads to an enrichment of pathogens of human and animal concern in the affected environments, or simply an increase in resistant environmental bacteria with little or no risk to human and animal health. Through our Indian partners we will disseminate our findings to the wider Indian scientific community and also to local communities in the vicinity of the production plants we are working on. Our data will feed into public information campaigns via our excellently connected Indian partners.

Novel mechanisms of resistance: Our data has the potential to identify novel mechanisms of resistance to clinically relevant antibiotics via the pleiotropic effects cytotoxic chemicals present in waste. This data has potential significance to the wider infectious disease community, in particular if compounds are present in other drugs which may impact treatment regimens during infectious disease treatment. The IMI has academic clinical lecturers who work in one of the UK's foremost ID clinics at Heartlands hospital and we will communicate our key findings to the ID team via regular research meetings we hold with the two entities. Our data also has the potential to identify chemical entities with previously unknown microbicidal properties. In the case that these may be of interest to biotech or pharma companies will will work with UoB Enterprise and Business engagement to tap into our wealth of industrial contacts to investigate further follow on projects.