Considering that AMPs are natural barriers to bacterial infections, pathogens ought to have developeda variety of strategies that render them resistant to antimicrobial host defenses.The only currently available structural model explaining the mechanism of action of AMPs , the action of these peptides is from the outside and over the pathogen’s membrane either by increasing their permeability  or by destabilizing membranes by changing the net charge of the composed  system. Since biological membranes are indeed dynamic fluids, the generation of resistance appears to be less likely to occur.  Nonetheless, pathogens have evolved countermeasures not to resist, but at least to limit AMPs’ effectiveness, such as chemical modifications and/or alternation of energy-dependent pumps at the membrane level (Peschel, 2002). The same is true for intracellular bacterial pathogens, in which resistance-limitation is less effective against mostly cationic peptide-driven antimicrobial activity existing in the phagosomes of circulating monocytes, neutrophils and some mucosal epithelial cells . Additionally, the fact that the common features for most peptides are a net positive charge and an amphipathic nature, allows them to persist at water-lipid interfaces and then to disturb microbial membrane components( Ruissen et al. 2001).

References

PESCHEL, A. How do bacteria resist human antimicrobial peptides? Trends in Microbiology, 2002, vol. 10, no. 4, p. 179-196.

RUISSEN, A.L.A.; GROENINCK, J.; HELMERHORST, E.J.; WALGREEN-WETERINGS, E.; VAN’T HOF, W.; VEERMAN, E.C.I. and NIEUW AMERONGEN, A.V. Effects of Histatin 5 and derived peptides on Candida albicans. Biochemical Journal,2001, vol. 356, no. 2, p. 361-368.

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