Strategy 1: Preventing access
Antimicrobial compounds almost always require access into the bacterial cell to reach their target site where they can interfere with the normal function of the bacterial organism. Porin channels are the passageways by which these antibiotics would normally cross the bacterial outer membrane. Some bacteria protect themselves by prohibiting these antimicrobial compounds from entering past their cell walls. For example, a variety of Gram-negative bacteria reduce the uptake of certain antibiotics, such as aminoglycosides and beta lactams, by modifying the cell membrane porin channel frequency, size, and selectivity. Prohibiting entry in this manner will prevent these antimicrobials from reaching their intended targets that, for aminoglycosides and beta lactams, are the ribosomes and the penicillin-binding proteins (PBPs), respectively.
This strategy have been observed in:
- Pseudomonas aeruginosa against imipenem (a beta-lactam antibiotic)
- Enterobacter aerogenes and Klebsiella spp. against imipenem
- Vancomycin intermediate-resistant S. aureus or VISA strains with thickened cell wall trapping vancomycin
- Many Gram-negative bacteria against aminoglycosides
- Many Gram-negative bacteria against quinolones