Antibiotic resistance (AMR) poses a threat to global health and Staphylococcus aureus has become one of the most notable multidrug-resistant pathogens, causing nearly 1 million deaths globally. S. aureus is found in 30% of the population, living in people’s nasal passages and on skin, and mostly it does not cause infection. Over the past 20 years however, there has been an increase in community-wide infections even among healthy individuals, bringing a sense of urgency to the global issue.
Scientists at the University of Bath have discovered a compound that inhibits methicillin-resistant Staphylococcus aureus (MRSA) and renders it more vulnerable to antibiotics.
The novel compound, a modified linear polyamine named AHA-1394, had been found to disrupt the bacterium’s membrane, and shows >128-fold increase in inhibition against S. aureus strains compared to the natural active polyamine.
Polyamines are small polycationic molecules involved in cellular functions in eukaryotes and bacteria, and their diversity of function is thought to be due to the uniform distribution of positive charges across a hydrophobic backbone.
The compound was tested in vitro against 10 different antibiotic-resistant strains of S. aureus and found it was successful against all strains. The compound could restore the sensitivity of multidrug resistant strains of the bacteria to three important antibiotics (daptomycin, oxacillin, and vancomycin). Preliminary research with the liver-derived HepG2 cell line suggests the compound is non-toxic to humans, but next studies will investigate the mechanisms used by the compound to inhibit S. aureus. The compound was also tested against biofilms, and was even able to prevent the formation of new biofilms, inhibiting biofilm-forming isolate SH1000 at a concentration of 16 µg/ml.
The new compound demonstrates that polyamine derivatives could have important implications in a clinical settings and we look forward to hearing more about them in future studies.
Reference
Douglas EJA et al (2022) Antibacterial activity of novel linear polyamines against Staphylococcus aureus. Front. Microbiol. Link