Peptide Nucleic Acids as Potential Designer Antimicrobials

Overview

The overuse of antibiotics in many aspects of daily life - from household cleaners to hand soaps - has ushered in a wave of resistance to antibiotics that have been successful for decades. Resistance to antibiotics is spread between bacteria through various mechanisms of gene transfer and mutation but can be prevented through antisense therapy, or gene regulation, to monitor and reverse resistance. Peptide nucleic acids (PNAs) are 8-10 synthetic nucleotide sequences complementary to the starting sequence of a given gene synthesized with a peptide backbone as opposed to the standard ribose backbone. They can be used to inhibit specific protein synthesis by binding to the target gene as well as associated mRNA and can be designed to target essential genes and resistance mechanisms in bacteria. In this experiment, PNA treatments were targeted for the essential gene tsf and the associated tetracycline resistance mechanism TetA in Salmonella typhimurium. These synthetic molecules, attached to cell-penetrating peptides (CPPs) to facilitate uptake into the cell, were incubated with Salmonella typhimurium for 18 hours in Mueller-Hinton Broth and a range of tetracycline concentrations to determine changes in the minimal inhibitory concentration and minimal bactericidal concentration of tetracycline in the presence of the PNA treatments. S. typhimurium was also incubated with a control PNA sequence that was nonspecific to the S. typhimurium genome and CPPs to determine their effects, if any, on S. typhimurium and separate them from the effects of the PNA treatments. It was discovered that PNA treatments targeting tsf and TetA are significantly inhibitory to bacterial growth after 4 h of incubation, decreasing in effectiveness as incubation period increases. Level of inhibition was discovered to be primarily affected by incubation period and concentration of tetracycline. Treatment groups also displayed a lower minimum inhibitory concentration and minimum bactericidal concentration than the bacterial growth control.

Competition history

• AJAS 2019 Category not listed

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