Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Antibiotics have been a mainstay of modern medicine of the last 60 years and have been the principle means of treating infections. Although not a new problem, there is increasing evidence that antibiotics are becoming less effective in certain settings, due to the emergence of bacteria which are no longer susceptible to treatment with antibiotics. This is defined as antibiotic / antimicrobial resistance, AMR. In recent years there has been a rapid rise in bacteria which are resistant to multiple antibiotics, leading in some cases, to essentially untreatable infections associated with high mortality. These so-called multidrug resistant (MDR) bacteria come from a variety of different species and are a major cause for concern. There are a wide range of documents which aim to define this phenomenon, understand what impact it will have on public health worldwide, estimate the likely costs of AMR and identify solutions to the problem. These include research strategy documents from the Department of Health and Social Care, a review of AMR commissioned by the UK government (the AMR Review chaired by Lord O'Neil) and recent documents from the World Health Organisation, European Union, and Centres for Disease Control in the US. A common feature in AMR is the ability of bacteria to increase the presence or abundance of certain proteins which are able to pump an antibiotic out of the bacterial cell, which stops them working. These so-called "efflux pumps" are common and can work on many different types of antibiotic. Although an attractive approach would be block these pumps to stop them working, using efflux-pump inhibitors (EPIs), this has proved to be difficult to achieve. This is at least partly due to the toxicity of some of the drugs that have been tried in this context. The project team have developed a new approach which uses state of the art computational methods to identify where and how different molecules bind to the efflux pumps. The team identified that inhibitors bind to specific parts of the pump which are different from antibiotics that may be exported through the pump. This has led to a new approach, where hybrid molecules are made, which keep the active part of the antibiotic and add on specific parts of the inhibitor molecule. This means the modified antibiotics can no longer be exported from the cell, which makes them work better. This approach is applied here to a new class of antibiotics that have not been used in the clinic previously and this potentially allows us to bring a new class of antibiotics into clinical use. We will focus on a high priority group of bacteria, which were identified previously by WHO as those most urgently needing new antibiotics. These bacteria are associated with lung infections, especially in hospital environments, and patients who are infected may have very poor outcomes with current treatment. Although focussed on a very specific class of new antibiotics, the method can be used with other types of antibiotic and we have already proved this in the laboratory. This means that findings from this study may be useful for other drug developers and may contribute to improved approaches for antibiotic development.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Monkeypox (MPX) is a viral infection caused by monkeypox virus, previously largely confined to West and Central Africa, with occasional infections arising from international travel. Most cases before 2022 are likely due to people encountering animals who are infected with the virus, likely a rodent but possible many animals that live in West and Central Africa. However, since May 2022 there has been a large outbreak all over the world, largely affected gay, bisexual and other men who have sex with men (GBMSM). By the end of August 2022, over 3,200 cases had been diagnosed in the UK. There has been sustained human-to-human transmission, showing that infection is spreading from person to person rather than needing people to encounter an infected animal. Monkeypox is predominantly spread from close contact, likely from exposure to skin lesions (spots) or recently contaminated bedsheets of an infected person. The previous monkeypox infection looks a lot like smallpox, or chickenpox, with lesions (or raised spots which can turn into blisters filled with fluid) all over the body. In this new 2022 outbreak, people have been diagnosed with far fewer spots, presenting to sexual health services with limited spots in the groin region, or small ulcers that may go undiagnosed. It is not known how often people may be infectious before the onset of any symptoms and development of spots, or indeed inf people can be infectious without ever knowing they have monkeypox infection (asymptomatic infection). This is vital to our understanding of how well different control measures will work. If people are not infectious without obvious spots or symptoms, they will be able to be told what symptoms to look out for that means they should seek medical attention, particularly if they have been in close contact with someone who has had monkeypox infection (a case). If many people can be infectious without knowing it, this will severely limit the impact of messaging to be aware of symptoms to control any outbreak. Control will only be possible by achieving population level vaccination coverage with a highly effective vaccine, or by considerable change in behaviour. There is some previous evidence from smallpox, a related virus, and from prior antibody studies in West Africa that have shown likely asymptomatic infection (or infection with unrecognised minor symptoms) disease in people who live in areas where monkeypox is known to exist. Monkeys are also known to be able to be infected without symptoms. From the current outbreak, early research in sexual health clinics in France and Belgium has shown that several people can likely be infected without ever displaying symptoms or have detectable infection before symptoms develop. There are also preliminary indications from a small number of cases that transmission may be occurring early in infection, which may include before individuals have identified that they are symptomatic. However there is no study to date that looks at a group of contacts of monkeypox cases to determine in detail a) how common this is b) how long people may be infectious for. We will attempt to answer these questions by asking close sexual contacts of monkeypox cases who have either been identified from public health contact tracing or from self-referral from online social media recruitment to take swabs and urine samples, along with blood tests to look for antibodies, and answer an online questionnaire about symptoms and monkeypox exposure. We will also be able to compile these data to also get an estimate of how many contacts go on to develop monkeypox infection and for those who have been vaccinated, how effective the vaccine is. The study will be conducted through collaboration between laboratory teams at UKHSA, field epidemiology, immunisation, data processing, and statistical experts, relevant teams engaged in national incident response, sexual health peer experts, and academics in sexual health research.