Investigation of Modified Bacterial Cell Wall Response to Bacteriophage Infection

Bacteriophages (phages) are viruses that specifically infect bacteria. Bacterial cell surface attachment is a critical step in phage infection. Many phages that infect Gram-positive bacteria require the bacterial cell surface polymer wall teichoic acid (WTA) as a receptor. However, bacteria can modify their cell wall with D-alanine residues, which can interfere with phage binding.
D-alanine modifications to Gram-positive bacteria modulate surface charge as well ligand binding properties. The incorporation of D-alanine residues into the cell wall requires D-alanine:alanyl carrier protein ligase (DltA). This work demonstrates that a small molecule (D-alanylacylsulfamoyl adenosine) inhibitor of DltA, can improve phage infectivity in Bacillus subtilis. This
small molecule inhibitor may have many applications in understanding bacteria-phage interactions and in supplementing antimicrobial phage therapies.

Herein, I also demonstrated in separate research that a combined genome mining and mass spectrometry approach led to the discovery of putative nucleoside natural product in Streptomyces lomondensis, which awaits comprehensive structure elucidation.