A new class of synthetic molecules is being engineered to kill Salmonella bacteria that have stopped responding to existing antibiotics. These molecules, called Strathclyde Minor Groove Binders (S-MGBs), work by binding to bacterial DNA in multiple places, but until recently they were ineffective against Gram-negative bacteria such as Salmonella. The project aims to design improved S-MGBs, test them against Salmonella strains from Thailand and Malaysia, and understand how they kill the bacteria by tracking changes in gene expression and observing their uptake into cells using microscopy. This matters because Salmonella infections cause fever, diarrhoea, and vomiting worldwide, and in Southeast Asia they have become a critical health burden as antimicrobial resistance (AMR) spreads rapidly. The World Health Organization has identified novel drug classes as a priority for tackling AMR, and S-MGBs have been externally verified as meeting that criterion. If successful, the research could produce a new treatment for drug-resistant Salmonella infections, reducing the threat of untreatable food poisoning for vulnerable people. The project also includes a sustained STEM outreach programme for school students in Scotland, Malaysia, and Thailand, aiming to raise global awareness of AMR.
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Salmonella spp., a Gram-negative bacterium, is a leading cause of global foodborne bacterial infection. Symptoms include fever, diarrhoea, vomiting and abdominal cramps, however the infection has become life-threatening to people with weakened immune systems. The majority of worldwide non-typhoidal foodborne Salmonellosis is caused by S. enteritidis and S. typhimurium. In Southeast Asia, Thailand and Malaysia in particular, Salmonella infections have remained a crucial health burden due to rapid antimicrobial resistance (AMR) in the region. Tackling these problematic infections is aligned with the WHO’s Global Action Plan on the AMR. Strathclyde Minor Groove Binders (S-MGBs) are an anti-infective platform that has successfully delivered molecules that are potent against a wide range of pathogenic organisms, including bacteria, fungi, parasites and viruses. The molecule class has been externally verified as ‘novel’ according to WHO criteria, which is an important aspect of dealing with AMR. However, until now S-MGBs have demonstrated limited activity against Gram-negative bacteria. Recently, researchers from the University of Strathclyde have identified several promising, and novel, S-MGB molecule types with improved activity against Gram-negative pathogens, including Salmonella spp. In this project, we aim to enhance the capability of newly developed S-MGB molecules against Salmonella spp. and to increase awareness of global AMR though STEM education. Specific objectives to achieve these goals include : 1) to design and make improved S-MGB molecules, and test their effectiveness against Gram-negative pathogens, principally Salmonella spp., and their cytotoxicity against mammalian cells. 2) to gain insight into how these new S-MGB molecules kill bacterial pathogens by looking for differences in the gene expression of Salmonella spp. after exposure to S-MGB molecules, and by monitoring their uptake into bacteria using microscopy. 3) to deliver a sustained programme of STEM outreach to school students in Scotland, Malaysia and Thailand.
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