EXPLORING TEN ESSENTIAL GENES IN METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) AS A POTENTIAL TARGET FOR NOVEL THERAPY

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infections are becoming progressively challenging to treat, due to acquired antibiotic resistance. The widespread epidemic of MRSA significantly limits effective therapeutic options. A new therapeutic strategy with a novel mechanism to eradicate MRSA is urgently required. Any essential and favorably conserved gene that is required for bacterial survival could be inhibited using peptide nucleic acid (PNA) as antisense. The PNAs will be conjugated to the traditional cell penetrating-peptide for Staphylococcus aureus, KITKFIFKITK. In the same manner, the cell penetrating peptide 8-mer amphipathic trans-acting polythymidylic thiophosphate triester element (dTtaPS) will be tested for the first time with prokaryotic cells. PNA will target the mRNA of the essential genes in an antisense mechanism and prevent the translation of these genes which ultimately leads to the bacterial death. The central hypothesis is that targeting the start codon region in any essential genes for survival of MRSA is an alternative therapeutic mechanism to using antibiotics. The long-term goal is to identify a gene that can be inhibited with a minimum inhibitory concentration of PNA and low, off-target effect. This gene could be the target for a novel therapy to fight MRSA.