Mechanism of Interaction of Different Classes of Cationic Antimicrobial Peptides with Planar Bilayers and with the Cytoplasmic Membrane ofEscherichia coli†

Cationic antimicrobial peptides (CAMPs) can be considered as new potential therapeutic agents for Tuberculosis treatment with a specific amino acid sequence. New studies can be developed in the future to improve the pharmacological properties of CAMPs and also understand possible resistance mechanisms. This review discusses the principal properties of natural and/or synthetic CAMPs, and how these new peptides have a significant specificity for Mycobacterium tuberculosis. Also, we propose some alternative strategies to enhance the therapeutic activity of these CAMPs that include coadministration with nanoparticles and/or classic drugs.

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The Lactococcal dgkB (yecE) and dxsA Genes for Lipid Metabolism Are Involved in the Resistance to Cell Envelope-Acting Antimicrobials

International Journal of Molecular Sciences ◽

10.3390/ijms22031014 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1014

Author(s):

Aleksandra Tymoszewska ◽

Tamara Aleksandrzak-Piekarczyk

Keyword(s):

Antimicrobial Peptides ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Cytoplasmic Membrane ◽

Cross Resistance ◽

Resistant Bacteria ◽

Membrane Targeting ◽

Nucleotide Polymorphisms ◽

Next Generation ◽

Lipid Ii

The emergence of antibiotic-resistant bacteria led to an urgent need for next-generation antimicrobial agents with novel mechanisms of action. The use of positively charged antimicrobial peptides that target cytoplasmic membrane is an especially promising strategy since essential functions and the conserved structure of the membrane hinder the development of bacterial resistance. Aureocin A53- and enterocin L50-like bacteriocins are highly cationic, membrane-targeting antimicrobial peptides that have potential as next-generation antibiotics. However, the mechanisms of resistance to these bacteriocins and cross-resistance against antibiotics must be examined before application to ensure their safe use. Here, in the model bacterium Lactococcus lactis, we studied the development of resistance to selected aureocin A53- and enterocin L50-like bacteriocins and its correlation with antibiotics. First, to generate spontaneous resistant mutants, L.lactis was exposed to bacteriocin BHT-B. Sequencing of their genomes revealed single nucleotide polymorphisms (SNPs) in the dgkB (yecE) and dxsA genes encoding diacylglycerol kinase and 1-deoxy-D-xylulose 5-phosphate synthase, respectively. Then, selected mutants underwent susceptibility tests with a wide array of bacteriocins and antibiotics. The highest alterations in the sensitivity of studied mutants were seen in the presence of cytoplasmic membrane targeting bacteriocins (K411, Ent7, EntL50, WelM, SalC, nisin) and antibiotics (daptomycin and gramicidin) as well as lipid II cycle-blocking bacteriocins (nisin and Lcn972) and antibiotics (bacitracin). Interestingly, decreased via the SNPs accumulation sensitivity to membrane-active bacteriocins and antibiotics resulted in the concurrently increased vulnerability to bacitracin, carbenicillin, or chlortetracycline. It is suspected that SNPs may result in alterations to the efficiency of the nascent enzymes rather than a total loss of their function as neither deletion nor overexpression of dxsA restored the phenotype observed in spontaneous mutants.

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Membrane targeting cationic antimicrobial peptides

Journal of Colloid and Interface Science ◽

10.1016/j.jcis.2018.10.103 ◽

2019 ◽

Vol 537 ◽

pp. 163-185 ◽

Cited By ~ 56

Author(s):

Daniela Ciumac ◽

Haoning Gong ◽

Xuzhi Hu ◽

Jian Ren Lu

Keyword(s):

Antimicrobial Peptides ◽

Membrane Targeting ◽

Cationic Antimicrobial Peptides

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Cationic Antimicrobial Peptides in Penaeid Shrimp

Marine Biotechnology ◽

10.1007/s10126-011-9381-8 ◽

2011 ◽

Vol 13 (4) ◽

pp. 639-657 ◽

Cited By ~ 65

Author(s):

Anchalee Tassanakajon ◽

Piti Amparyup ◽

Kunlaya Somboonwiwat ◽

Premruethai Supungul

Keyword(s):

Antimicrobial Peptides ◽

Penaeid Shrimp ◽

Cationic Antimicrobial Peptides

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Generation of novel cationic antimicrobial peptides from natural non-antimicrobial sequences by acid-amide substitution

Annals of Clinical Microbiology and Antimicrobials ◽

10.1186/1476-0711-10-11 ◽

2011 ◽

Vol 10 (1) ◽

pp. 11 ◽

Cited By ~ 9

Author(s):

Satoshi Ueno ◽

Masaomi Minaba ◽

Yuji Nishiuchi ◽

Misako Taichi ◽

Yasushi Tamada ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Acid Amide ◽

Cationic Antimicrobial Peptides

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A lack of synergy between membrane-permeabilizing cationic antimicrobial peptides and conventional antibiotics

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/j.bbamem.2014.09.010 ◽

2015 ◽

Vol 1848 (1) ◽

pp. 8-15 ◽

Cited By ~ 19

Author(s):

Jing He ◽

Charles G. Starr ◽

William C. Wimley

Keyword(s):

Antimicrobial Peptides ◽

Cationic Antimicrobial Peptides ◽

Conventional Antibiotics

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Bordetella pertussis Lipid A Glucosamine Modification Confers Resistance to Cationic Antimicrobial Peptides and Increases Resistance to Outer Membrane Perturbation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02590-14 ◽

2014 ◽

Vol 58 (8) ◽

pp. 4931-4934 ◽

Cited By ~ 19

Author(s):

Nita R. Shah ◽

Robert E. W. Hancock ◽

Rachel C. Fernandez

Keyword(s):

Immune System ◽

Antimicrobial Peptides ◽

Outer Membrane ◽

Bordetella Pertussis ◽

Lipid A ◽

Whooping Cough ◽

Human Immune System ◽

Cationic Antimicrobial Peptides ◽

Content Type ◽

Membrane Perturbation

ABSTRACTBordetella pertussis, the causative agent of whooping cough, has many strategies for evading the human immune system. Lipopolysaccharide (LPS) is an important Gram-negative bacterial surface structure that activates the immune system via Toll-like receptor 4 and enables susceptibility to cationic antimicrobial peptides (CAMPs). We show modification of the lipid A region of LPS with glucosamine increased resistance to numerous CAMPs, including LL-37. Furthermore, we demonstrate that this glucosamine modification increased resistance to outer membrane perturbation.

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