Lipoteichoic acid (LTA) is an important polymer localized on the surface of Gram-positive bacteria. Discovered approximately 60 years ago, LTA comprises as much as 15% of the Gram- positive cell envelop dry weight, and LTA-defective strains are often non-viable or display severe growth defects, suggesting that LTA plays an important role in bacterial physiology. In spite of LTA's importance in cell viability and how long we have known of its existence, our understanding of LTA's role in bacterial physiology and how it contributes to survival remains obscure. The overarching goal of this project is to fill this knowledge gap. Using the oral commensal Streptococcus gordonii as a model Gram-positive organism, we show that LTA is required for the localization of the adhesin-like lipoprotein ScaA on the cell wall. No effect in transcription or steady-state level of ScaA protein was detected in other cellular compartment, which led us to hypothesize that LTA serves a structural role in ScaA localization on the cell wall. To test this hypothesis, we will (i) investigate the mechanisms involved in the cell ?decision? to place ScaA on the cell wall, since lipoproteins like ScaA are expected to be retained within the cell membrane. (ii) We will determine whether ScaA directly binds LTA on the cell wall. And (iii) we will determine if LTA is involved in the cell wall localization of other proteins. These experiments will greatly enhance our understanding of this important Gram- positive structure and the underlying molecular mechanisms by which it affects surface-protein display, biofilm formation and, in some cases, cell viability.
Many Gram-positive bacteria like Clostridium difficile, Bacillus anthracis and Staphylococcus aureus cause severe human diseases and pose a significant burden to the health care system. Lipoteichoic acid (LTA) is a conserved surface structure on the cell surface of Gram-positive bacteria, and it has been shown to contribute to the virulence of some of these organisms. This proposal will identify LTA?s physiological role and provide new information that can be used against Gram-positive infections.