This project aims to develop a new antibiotic for the treatment of serious bacterial infections. Many antibiotics have been developed in the past, but over time bacteria are able to develop resistance to antibiotic drugs. Bacterial resistance has become a global concern, so new drugs are needed, especially ones against which it is hard for resistance to develop. Protein production is a key requirement for any life form, including bacteria, and there is a family of twenty enzymes involved in the key step of combining amino acids with RNA prior to attaching the correct amino acid to the growing protein chain. A drug compound that stops one of these enzymes working weakens the bacteria, allowing them to be mopped up by the body's defences. However, bacteria can evolve resistance to such inhibitors by making subtle changes to its DNA, leading to a modified version of the enzyme that is no longer blocked by the drug. This project aims to develop inhibitors that target more than one member of the enzyme family. By interfering with protein production at two independent points in the process, the bacteria are forced to evolve mutations in their DNA coding for two separate enzymes. The chances of this happening successfully are a tiny fraction of the possibility of becoming resistant to one enzyme, greatly reducing the chance of resistance developing against the drug.

The major threat to human health caused by growing antimicrobial resistance (AMR) has been much publicised. One factor contributing to this growth is that antibiotics used to treat humans are also widely used to treat farm (food) animals, providing an opportunity for resistance to develop and spread. Pressure from regulators and other measures have enabled substantial progress in decreasing the use of antibiotics in animals. However, the reduction has plateaued, and only small additional reductions can now be anticipated. Bacterial infections in animals continue to be a major detriment to their health and welfare, with a significant economic impact on farmers and a threat to the resilience of the sector. This leaves a substantial unmet need for developing new strategies to control infection in animals that do not pose a risk to human health. The aim of this project is to develop a new veterinary-only antibiotic that will not contribute to increased AMR against antibiotics used for human infections, thus representing a more sustainable alternative to antibiotics currently in use in farms. From our prior work, we have identified antibacterial compounds with high levels of activity against a major pathogen of pigs, _Streptococcus suis_, but with limited activity against pathogens causing human disease. These compounds work in a different way to existing antibiotics, that is, they possess a novel mode of action. Due to this different mode of action, any resistance developed to these antibiotics, if transferred to human pathogens, would likely not interfere with human therapy. Thus, such compounds could be used to meet the welfare needs of the animals, protect the economic needs of the farmers, and help secure the food supply without the risk of decreasing the effectiveness of human antibiotics. Our aim is to develop the compounds to a stage where they would represent an attractive licensing opportunity to one of the major animal health companies for regulatory development and marketing. This highly novel approach to developing a veterinary antibiotic can be applied to additional diseases of farm animals. Thus, we envisage that this initial project will be the basis for expansion to a pipeline of opportunities in other important animal health markets.

The emergence of resistance to antibiotics is a major health concern. To address this concern, this project will address multiple aspects of antibacterial resistance, bringing together complementary expertise in the UK and China. Antibiotics are widely used in agriculture, where they have a valid role in protecting farm animals from disease and increasing food production. However, the use of antibiotics that are also used to treat humans could lead to increased antimicrobial resistance. The aim of this project is to develop classes of antibiotic that are specific to a species of bacterium that cause infections in pigs. This which would enable reduced use of human antibiotics in farming and mean that animal welfare can be protected without the risk of further increasing antibiotic resistance to antibiotics important for the treatment of human infections .

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Awaiting Public Project Summary

The emergence of resistance to antibiotics is a major health concern. To address this concern, this project will address multiple aspects of antibacterial resistance, bringing together complementary expertise in the UK and China. Antibiotics are widely used in agriculture, where they have a valid role in protecting farm animals from disease and increasing food production. However, the use of antibiotics that are also used to treat humans could lead to increased antimicrobial resistance. One of the aims of this project is to develop a new class of antibiotics that are specific to a species of bacteria that cause infections in pigs, which would enable reduced use of human antibiotics in farming. A second aspect of the proposal is to investigate the use of traditional Chinese medicines (TCMs) in veterinary settings. TCMs are typically complex mixtures with unknown mechanism of action. We will use sophisticated computational modelling methods, specifically a technique called chemgenomics, to identify the active components of TCMs, which may enable further classes of antibiotic to be rationally designed, or to be used synergistically with existing compounds.

This project aims to develop a new antibiotic for the treatment of serious bacterial infections. Many antibiotics have been developed in the past, but bacteria have developed resistance to antibiotic drugs, so new drugs are urgently needed. Protein production is a key requirement for any life form, including bacteria, and there is a family of twenty enzymes involved in the key step of combining amino acids with RNA prior to attaching the correct amino acid to the growing protein chain. A drug that stops one of these enzymes working weakens the bacteria, allowing them to be mopped up by the body's defences. However, bacteria can evolve resistance to such inhibitors, leading to a modified version of the enzyme that is no longer blocked by the drug. This project aims to develop inhibitors that target more than one member of the enzyme family. By interfering with protein production at two independent points in the process, the bacteria are forced to evolve mutations in their DNA coding for two separate enzymes. The chances of this happening successfully are a tiny fraction of the possibility of becoming resistant to one enzyme, greatly reducing the chance of resistance developing against the drug.