multi-target dna binding: a novel approach to combat foodborne and amr bacteria

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.