Cationic Antimicrobial Peptides for Tuberculosis: A Mini-Review

2019 ◽  
Vol 20 (9) ◽  
pp. 885-892
Author(s):  
Sara Silva ◽  
Nuno Vale
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Resistance Mechanisms ◽  
Therapeutic Agents ◽  
Pharmacological Properties ◽  
Therapeutic Activity ◽  
Alternative Strategies ◽  
Cationic Antimicrobial Peptides ◽  
Specific Amino Acid

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.

scholarly journals Rational Design of Engineered Cationic Antimicrobial Peptides Consisting Exclusively of Arginine and Tryptophan, and Their Activity against Multidrug-Resistant Pathogens

2013 ◽  
Vol 57 (6) ◽  
pp. 2511-2521 ◽  
Author(s):  
Berthony Deslouches ◽  
Jonathan D. Steckbeck ◽  
Jodi K. Craigo ◽  
Yohei Doi ◽  
Timothy A. Mietzner ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Rational Design ◽  
Antimicrobial Agents ◽  
Divalent Cations ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Broth Culture ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Amphipathic Helices

ABSTRACTThe emergence of multidrug-resistant (MDR) pathogens underscores the need for new antimicrobial agents to overcome the resistance mechanisms of these organisms. Cationic antimicrobial peptides (CAPs) provide a potential source of new antimicrobial therapeutics. We previously characterized a lytic base unit (LBU) series of engineered CAPs (eCAPs) of 12 to 48 residues demonstrating maximum antibacterial selectivity at 24 residues. Further, Trp substitution in LBU sequences increased activity against bothP. aeruginosaandS. aureusunder challenging conditions (e.g., saline, divalent cations, and serum). Based on these findings, we hypothesized that the optimal length and, therefore, the cost for maximum eCAP activity under physiologically relevant conditions could be significantly reduced using only Arg and Trp arranged to form idealized amphipathic helices. Hence, we developed a novel peptide series, composed only of Arg and Trp, in a sequence predicted and verified by circular dichroism to fold into optimized amphipathic helices. The most effective antimicrobial activity was achieved at 12 residues in length (WR12) against a panel of both Gram-negative and Gram-positive clinical isolates, including extensively drug-resistant strains, in saline and broth culture and at various pH values. The results demonstrate that the rational design of CAPs can lead to a significant reduction in the length and the number of amino acids used in peptide design to achieve optimal potency and selectivity against specific pathogens.

Potent cationic antimicrobial peptides against Mycobacterium tuberculosis in vitro

2019 ◽  
Vol 19 ◽  
pp. 132-135 ◽  
Author(s):  
Sara Silva ◽  
Anabela Santos-Silva ◽  
José Manuel Correia da Costa ◽  
Nuno Vale
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimicrobial Peptides ◽  
Cationic Antimicrobial Peptides

scholarly journals Identification of 14-α-Lanosterol Demethylase (CYP51) in Scedosporium Species

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Anne Bernhardt ◽  
Wieland Meyer ◽  
Volker Rickerts ◽  
Toni Aebischer ◽  
Kathrin Tintelnot
Keyword(s):  
Amino Acid ◽  
Resistance Mechanisms ◽  
Upstream Region ◽  
Scedosporium Apiospermum ◽  
Gene Encoding ◽  
Specific Amino Acid ◽  
Content Type ◽  
Scedosporium Dehoogii ◽  
Lanosterol Demethylase ◽  
Species Specific

ABSTRACT Scedosporium spp. cause infections (scedosporiosis) in both immunocompetent and immunocompromised individuals and may persistently colonize the respiratory tract in patients with cystic fibrosis (CF). They are less susceptible against azoles than are other molds, such as Aspergillus spp., suggesting the presence of resistance mechanisms. It can be hypothesized that the decreased susceptibility of Scedosporium spp. to azoles is also CYP51 dependent. Analysis of the Scedosporium apiospermum and Scedosporium aurantiacum genomes revealed one CYP51 gene encoding the 14-α-lanosterol demethylase. This gene from 159 clinical or environmental Scedosporium isolates and three Lomentospora prolificans isolates has been sequenced and analyzed. The Scedosporium CYP51 protein clustered with the group of known CYP51B orthologues and showed species-specific polymorphisms. A tandem repeat in the 5′ upstream region of Scedosporium CYP51 like that in Aspergillus fumigatus could not be detected. Species-specific amino acid alterations in CYP51 of Scedosporium boydii, Scedosporium ellipsoideum, Scedosporium dehoogii, and Scedosporium minutisporum isolates were located at positions that have not been described as having an impact on azole susceptibility. In contrast, two of the three S. apiospermum-specific amino acid changes (Y136F and G464S) corresponded to respective mutations in A. fumigatus CYP51A at amino acid positions 121 and 448 (Y121F and G448S, respectively) that had been linked to azole resistance.

scholarly journals Targeting Mycobacterium tuberculosis and Other Microbial Pathogens Using Improved Synthetic Antibacterial Peptides

2013 ◽  
Vol 57 (5) ◽  
pp. 2295-2303 ◽  
Author(s):  
Santiago Ramón-García ◽  
Ralf Mikut ◽  
Carol Ng ◽  
Serge Ruden ◽  
Rudolf Volkmer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
Antimicrobial Peptides ◽  
Fungal Pathogens ◽  
Antimicrobial Activities ◽  
Microbial Pathogens ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Activity Spectrum ◽  
Low Cytotoxicity

ABSTRACTThe lack of effective therapies for treating tuberculosis (TB) is a global health problem. WhileMycobacterium tuberculosisis notoriously resistant to most available antibiotics, we identified synthetic short cationic antimicrobial peptides that were active at low micromolar concentrations (less than 10 μM). These small peptides (averaging 10 amino acids) had remarkably broad spectra of antimicrobial activities against both bacterial and fungal pathogens and an indication of low cytotoxicity. In addition, their antimicrobial activities displayed various degrees of species specificity that were not related to taxonomy. For example,Candida albicansandStaphylococcus aureuswere the best surrogates to predict peptide activity againstM. tuberculosis, whileMycobacterium smegmatiswas a poor surrogate. Principle component analysis of activity spectrum profiles identified unique features associated with activity againstM. tuberculosisthat reflect their distinctive amino acid composition; active peptides were more hydrophobic and cationic, reflecting increased tryptophan with compensating decreases in valine and other uncharged amino acids and increased lysine. These studies provide foundations for development of cationic antimicrobial peptides as potential new therapeutic agents for TB treatment.

scholarly journals Novel peptide therapeutics for treatment of infections

2009 ◽  
Vol 58 (8) ◽  
pp. 977-987 ◽  
Author(s):  
P. C. F. Oyston ◽  
M. A. Fox ◽  
S. J. Richards ◽  
G. C. Clark
Keyword(s):  
Antimicrobial Peptides ◽  
Therapeutic Agents ◽  
Innate Immune ◽  
Antimicrobial Compounds ◽  
Peptide Therapeutics ◽  
Cationic Antimicrobial Peptides ◽  
Immune Effector ◽  
New Approaches ◽  
Innate Immune Effector ◽  
Topical Applications

As antibiotic resistance increases worldwide, there is an increasing pressure to develop novel classes of antimicrobial compounds to fight infectious disease. Peptide therapeutics represent a novel class of therapeutic agents. Some, such as cationic antimicrobial peptides and peptidoglycan recognition proteins, have been identified from studies of innate immune effector mechanisms, while others are completely novel compounds generated in biological systems. Currently, only selected cationic antimicrobial peptides have been licensed, and only for topical applications. However, research using new approaches to identify novel antimicrobial peptide therapeutics, and new approaches to delivery and improving stability, will result in an increased range of peptide therapeutics available in the clinic for broader applications.

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