biostudies-literatureUnknown13Douglas EJANew therapeutic options are urgently required for the treatment of <i>Staphylococcus aureus</i> infections. Accordingly, we sought to exploit the vulnerability of <i>S. aureus</i> to naturally occurring polyamines. We have developed and tested the anti-staphylococcal activity of three novel linear polyamines based on spermine and norspermine. Using a panel of genetically distinct and clinically relevant multidrug resistant <i>S. aureus</i> isolates, including the polyamine resistant USA300 strain LAC, compound AHA-1394 showed a greater than 128-fold increase in inhibition against specific <i>S. aureus</i> strains compared to the most active natural polyamine. Furthermore, we show that AHA-1394 has superior biofilm prevention and biofilm dispersal properties compared to natural polyamines wFrontiers in microbiology948343https://www.ebi.ac.uk/biostudies/studies/S-EPMC9441809biostudies-literatureAntibacterial activity of novel linear polyamines against <i>Staphylococcus aureus</i>.PMC9441809Li SWoodman TJAlkhzem AHWonfor TLaabei MDouglas EJABlagbrough ISfalseAntibacterial activity of novel linear polyamines against <i>Staphylococcus aureus</i>.New therapeutic options are urgently required for the treatment of <i>Staphylococcus aureus</i> infections. Accordingly, we sought to exploit the vulnerability of <i>S. aureus</i> to naturally occurring polyamines. We have developed and tested the anti-staphylococcal activity of three novel linear polyamines based on spermine and norspermine. Using a panel of genetically distinct and clinically relevant multidrug resistant <i>S. aureus</i> isolates, including the polyamine resistant USA300 strain LAC, compound AHA-1394 showed a greater than 128-fold increase in inhibition against specific <i>S. aureus</i> strains compared to the most active natural polyamine. Furthermore, we show that AHA-1394 has superior biofilm prevention and biofilm dispersal properties compared to natural polyamines w2022-01-01T00:00:00Z20222026-05-27T18:44:07.108Z2025-04-05T10:59:26.533ZS-EPMC94418093607195710.3389/fmicb.2022.948343