Novel inter-disciplinary approaches for identifying and tackling the spread of AntiMicrobial Resistance through Environmental pathways in PAKistan

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Medicine has been transformed by the development of antibiotics, medicines that kill bacteria. These have made deadly bacterial diseases that once killed millions such as tetanus, syphilis, and leprosy, easily treatable. They are given as a preventative measure prior to surgery to prevent infection and they relieve suffering from less dangerous diseases such as strep throat. There is, however, a problem. Bacteria are becoming resistant to antibiotics. This is a result of evolution. The use of antibiotics inevitably selects for bacteria that carry genes that can protect them against these compounds. We call these antibiotic or antibacterial resistance genes (ARGs). Genes are pieces of DNA that make up part of the bacteria's genome or smaller DNA molecules such as plasmids. ARGs provide bacteria with the ability to degrade or excrete antibiotics. They can be exchanged between different species of bacteria allowing these abilities to spread through communities.The use and misuse of antibiotics is accelerating the rate at which ARGs evolve and spread. Using antibiotics to treat non-bacterial infections or to improve the growth rate of livestock results in large amounts of antibiotics entering the environment, this creates a strong selective pressure leading to many resistant bacteria. This resistance can develop in free-living bacteria that perform important functions in ecosystems, e.g. soils or rivers, but then spread to bacteria that cause disease within humans, pathogens. There are pathogens beginning to appear that are resistant to multiple antibiotics, e.g. multidrug-resistant tuberculosis. If this multi-drug resistance spreads further then diseases that are now treatable will become increasingly deadly. This is a potential global public health disaster. The problems caused by antibiotic resistance (ABR) will particularly badly impact Low and Middle Income Countries (LMICs), such as Pakistan, that depend upon cheap antibiotics to treat many infectious diseases. Tragically, it is just these countries, which are likely to have the most problems. This is because antibiotics are easily available without prescription over the counter. People take antibiotics to treat non-bacterial diseases or do not take them for long enough, this allows the resistant bacteria to spread and proliferate. This is compounded by manufacturers of antibiotics releasing wastewater contaminated with antibiotics into the environment, farmers using large quantities of antibiotics in intensive livestock rearing, and the fact that human and animal waste is dumped untreated into water sources. All this pollution results in more resistant bacteria evolving. It is unclear, however, which of these factors are most important to address, in order to prevent the spread of ABR.We have assembled a team of biologists, engineers, social scientists and mathematicians, to better understand ABR in Pakistan and how to combat it. We will conduct a survey of resistance genes across multiple areas within Pakistan, chosen in order to determine what causes them to proliferate and spread, ultimately leading to drug-resistant infections in humans. We will do this by sequencing DNA direct from environmental samples to resolve the genes that are present in the bacteria. We will sample from the environment and from a range of health facilities to reveal how genes are being transmitted from environmental bacteria into pathogens. We will also study the behaviour of people and institutions in Pakistan and determine how that contributes to the scale of the problem. This will allow us to propose ways in which they can reduce the spread of antibiotic resistant genes. These might be changes to how antibiotics are used in health facilities or improved approaches to waste disposal. This will be of great benefit to Pakistan but also - because these genes are capable of spreading between individuals across the world - to other LMICs and us in the UK too.