Antimicrobial Peptides - Bacterial Resistance

Bacterial Resistance

Bacteria use various resistance strategies to avoid antimicrobial peptide killing. Some microorganisms alter net surface charges. Staphylococcus aureus transports D-alanine from the cytoplasm to the surface teichoic acid to reduce the net negative charge by introducing basic amino groups. S. aureus also modifies its anionic membranes via MprF with L-lysine, increasing the positive net charge. The interaction of antimicrobial peptides with membrane targets can be limited by capsule polysaccharide of Klebsiella pneumoniae. Alterations occur in Lipid A. Salmonella species reduce the fluidity of their outer membrane by increasing hydrophobic interactions between an increased number of Lipid A acyl tails by adding myristate to Lipid A with 2-hydroxymyristate and forming hepta-acylated Lipid A by adding palmitate. The increased hydrophobic moment is though to retard or abolish antimicrobial peptide insertion and pore formation. The residues undergo alteration in membrane proteins. In some Gram-negative bacteria, alteration in the production of outer membrane proteins correlates with resistance to killing by antimicrobial peptides. Nontypeable Hemophilus influenzae transports AMPs into the interior of the cell, where they are degraded. And H. influenzae remodels its membranes to make it appear as if the bacterium has already been successfully attacked by AMPs, protecting it from being attacked by more AMPs. ATP-binding cassette transporters import antimicrobial peptides and the resistance-nodulation cell-division efflux pump exports antimicrobial peptides. Both transporters have been associated with antimicrobial peptide resistance. Bacteria produce proteolytic enzymes,which may degrade antimicrobial peptides leading to their resistance.

While these examples show that resistance can evolve naturally, there is increasing concern that using pharmaceutical copies of antimicrobial peptides can make resistance happen more often and faster. Worse, Research has found that, in some cases, resistance to these peptides used as a pharmaceutical to treat medical problems can lead to resistance not only to the medical application of the peptides, but to the body's own use of those peptides. Further research is needed to determine if this will lead to greater harm than benefit from the use of certain antimicrobial peptides.