Potentiating effects of leaderless enterocin DD14 in combination with methicillin on clinical methicillin-resistant Staphylococcus aureus S1 strain

Microbiol Res. 2021 Nov:252:126864. doi: 10.1016/j.micres.2021.126864. Epub 2021 Sep 9.


Biofilm formation by pathogenic bacteria as well as their resilience to antibiotic treatments are a major health problem. Here, we sequenced and analyzed the genome of the clinical methicillin-resistant Staphylococcus aureus S1 (MRSA-S1) strain and established its sensitivity to the combination of methicillin and the leaderless two peptides enterocin DD14 (EntDD14). Such sensitivity was assessed in vitro based on the MIC/FIC values as well as on killing curves experiments. Moreover, combination of EntDD14 and methicillin was able to reduce the biofilm formation of Staphylococcus aureus S1 of about ∼30 %. Interestingly, genes thought to be involved in the virulence of MRSA-S1, like nuc and pvl which code, respectively, for nuclease and Panton-Valentine leucocidin, were shown to be downregulated following treatment with EntDD14 and methicillin. Similar effects were registered for other genes such as cflA, cflB and icaB, coding for bacterial ligands clumping factors A, B and intercellular adhesion factor respectively. All these data, suggest that combinations of bacteriocins and antibiotics are useful as a backup for treatment of bacterial infections.

Keywords: Anti-biofilm activity; Enterocin DD14; Methicillin; Methicillin resistant Staphylococcus aureus MRSA; Synergy; Virulence and biofilm genes expression.

MeSH terms

  • Bridged-Ring Compounds / pharmacology
  • Drug Resistance, Bacterial* / drug effects
  • Drug Synergism*
  • Methicillin* / pharmacology
  • Methicillin-Resistant Staphylococcus aureus* / drug effects


  • Bridged-Ring Compounds
  • enterocin
  • Methicillin