Please see my image. I have read that aminoglycoside antibiotics disrupt the lipopolysaccharide barrier in bacteria by replacing calcium and magnesium with their amines. Normally calcium and magnesium are thought to stabilize the LPS through crossbridging anionic groups. Also, aminoglycosides do not work well or penetrate bacteria well in acidic pH. Based on the pKa values of the amines on aminoglycosides (see image) I am think that at low pH the aminoglycoside has so many positive charges that it will form its own crosslinks and form a barrier to further penetration, whereas when it is only singly charged or at least not fully charged on all amines I am wondering if it can replace the calcium and magnesium, but not form crosslinks, thereby disrupting the barrier, and not forming its own barrier. From everything I have read I still do not have a conclusive answer as to why low pH impairs aminoglycoside penetration and effectiveness. I don't believe the proton motive force argument holds up at all, because lowering the pH increased the proton motive force.

I wish I had time to study this myself.