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Background  Antibiotic resistance genes can be targeted by antisense agents, which can reduce their expression and thus restore cellular susceptibility to existing antibiotics. Antisense inhibitors can be gene and pathogen specific, or designed to inhibit a group of bacteria having conserved sequences within resistance genes. Here, we aimed to develop antisense peptide nucleic acids (PNAs) that could be used to effectively restore susceptibility to β-lactams in methicillin-resistant  Staphylococcus aureus  (MRSA) and methicillin-resistant  Staphylococcus pseudintermedius  (MRSP).    Results  Antisense PNAs specific for conserved regions of the mobilisable gene  mecA , and the growth essential gene,  ftsZ , were designed. Clinical MRSA and MRSP strains of high oxacillin resistance were treated with PNAs and assayed for reduction in colony forming units on oxacillin plates, reduction in target gene mRNA levels, and cell size. Anti- mecA  PNA at 7.5 and 2.5 μM reduced  mecA  mRNA in MRSA and MRSP ( p  < 0.05). At these PNA concentrations, 66 % of MRSA and 92 % of MRSP cells were killed by oxacillin ( p  < 0.01). Anti- ftsZ  PNA at 7.5 and 2.5 μM reduced  ftsZ  mRNA in MRSA and MRSP, respectively ( p  ≤ 0.05). At these PNA concentrations, 86 % of MRSA cells and 95 % of MRSP cells were killed by oxacillin ( p  < 0.05). Anti- ftsZ  PNAs resulted in swelling of bacterial cells. Scrambled PNA controls did not affect MRSA but sensitized MRSP moderately to oxacillin without affecting mRNA levels.    Conclusions  The antisense PNAs effects observed provide in vitro proof of concept that this approach can be used to reverse β-lactam resistance in staphylococci. Further studies are warranted as clinical treatment alternatives are needed.    Electronic supplementary material  The online version of this article (doi:10.1186/s12866-015-0599-x) contains supplementary material, which is available to authorized users.

bmc microbiology

Oxacillin sensitization of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius by antisense peptide nucleic acids in vitro