Mechanisms and consequences of bacterial resistance to antimicrobial peptides.
By D. Andersson, D. Hughes, Jessica Z. Kubicek-Sutherland. Drug resistance updates, 2016
623 citations recorded by the source corpus.
Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.
Subfields: Food Science, Microbiology
View Paper: https://www.semanticscholar.org/paper/c64ad74e2552dadd125b2b5f3fa09b607293333d
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In Food Science
In Microbiology
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- Suzana K. Straus
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Citations in the corpus
- Antimicrobial Peptides: An Emerging Category of Therapeutic Agents (2016, background): “The detailed discussion on the underlying mechanisms and consequences of microbial resistance to AMPs is beyond the scope of this review, and the reader is referred to the excellent recent review by Andersson et al. (2016).”
- Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo (2018, background): “After the initial electrostatic and hydrophobic interactions, the AMPs accumulate at the surface and self-assemble on the bacterial membrane after reaching a certain concentration [95,96].”
- The antimicrobial activity of nanoparticles: present situation and prospects for the future (2017, background): “…enzymes; 3) the use of active efflux pump systems; 25,26 4) the presentation of obstacles to antibiotic permeation; 5) the formation of biofilms; 27 and 6) the emergence and elimination of a specific protein, such as BamA 28 or KatG, 29 which can affect infection through unknown mechanisms.”