The Effects of the Unnatural Amino Acid TTO- 53 on the Biofilm of Staphylococcus aureus

Abstract

There are over 30 different species of staphylococci and many cause infection that can lead to hospitalization or death. The member most associated with chronic infection is Staphylococcus aureus. Staphylococcus aureus is a Gram-positive bacterium and usually harmless. It can be found on the skin of 15-40% of people in America. S. aureus spreads through contact with contaminated surfaces and skin to skin contact. Additionally, S. aureus has evolved a number of strategies to become more resistant to antibiotics. One strategy important to facilitating antibiotic resistance and resisting unfavorable environmental changes is biofilm. Biofilm is an extracellular matrix made up of extracellular DNA, proteins, and polysaccharides and acts as extra protection for the bacteria cells. Biofilm development happens in three phases, attachment, maturation, and dispersal phase. During attachment, cells aggregate due to poly-N-acetylglucosamine introducing a positive charge to the negatively charged bacteria. Cells will mature and aggregate through cell-to-cell communication with the use of autoinducer, using a regulatory system known as quorum sensing. Quorum sensing is regulated by a large number of genes involved in both assembly and disassembly. We have previously demonstrated that an unnatural amino acid, TTO-53 is able to disrupt biofilm in a several other organisms. The goal of this research was to determine if TTO- 53 demonstrates similar effects on the biofilm of Staphylococcus aureus and how this is occurring. Our data indicated that there are disruptive effects occurring in biofilm when TTO-53 is introduced to the environment. This disruption is not due to cell death. There is evidence that TTO-53 is impacting regulation of several biofilm genes. But it is still unknown how TTO-53 is causing disruption.