In: Biology
Gram-negative:
I would target the ATPases (e.g. the ATPase LptA) of the protein-assembly (e.g. LptABCDEFG) involved in transporting components of the lipopolysaccharide( LPS) layer. The LPS of gram-negative bacteria, which is made up of Lipid A, oligosaccharides, and core antigen polysaccharide chains, is the major constituent of the outer membrane of gram-negative bacteria. The outer membrane restricts access to molecules over 600 Da including many of the antibiotics that target prokaryotic genetic pathways. So, inhibiting the formation of this layer is highly useful in controlling its lethality and resistance. If LPS goes away the cell wall loses its ordered structure and its charge, its protection from lethal chemicals, and eventually, the cell dies.
Gram-positive:
I would target the late-stage enzymes of the biosynthesis pathway of wall teichoic acid. Wall teichoic acids are bound covalently with peptidoglycan molecules in gram-positive bacteria and provide negative charges to the structure. It has roles in biofilm production, host adhesion, cell elongation, and cation-binding( which helps reducing repulsion from neighboring bacteria) among others. Thus, inhibition of wall teichoic acid can render the bacteria extremely vulnerable. In fact, it has been shown that inhibition of late-stage enzymes in wall teichoic acid pathway stops the growth of the bacteria.