Potential Binding Sites of Toluidine Blue O in Gram-Positive Bacterial Membrane Wall Teichoic Acid: Modeling Approach

Photodynamic therapy (PDT) introduces a promising alternative to traditional antibiotics. However, the mechanism of binding the photosensitizers (PSs) to the bacterial cells and their specific cellular localization is not fully understood. The importance of understanding the mechanism of binding comes from two reasons. The first one is: the binding site is expected to be the place of the first damage of the photodynamic effect. This helps in understanding the mechanism of action. This moves us forward to the second reason, which is, by developing our understanding of the PDT mechanism, we can know and avoid the potential resistance pathways by bacteria. This study chooses one of the promising photosensitizers, toluidine blue O (TBO), to study its binding with a single membrane component, teichoic acid. Teichoic acid (TA) is a potential binding target in the Gram-positive bacterial membrane. By applying to model using the semi-empirical SP3 method to find out the potential binding interaction between single TA and single TBO molecules, we find that the nitrogen atom in the middle ring of the TBO molecule is the most probable to be the root of interaction with the TA molecule. While OH groups in the TA structure are the most likely site of interaction with TBO.