Mechanisms and Significance of Bacterial Resistance to Human Cationic Antimicrobial Peptides

2012 ◽  
pp. 219-254 ◽  
Author(s):  
Maira Goytia ◽  
Justin L. Kandler ◽  
William M. Shafer
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Cationic Antimicrobial Peptides

scholarly journals Bactofencin A, a New Type of Cationic Bacteriocin with Unusual Immunity

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Eileen F. O'Shea ◽  
Paula M. O'Connor ◽  
Orla O'Sullivan ◽  
Paul D. Cotter ◽  
R. Paul Ross ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Gene Cluster ◽  
Bacterial Resistance ◽  
Intestinal Bacteria ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Immunity Gene ◽  
New Type ◽  
Porcine Origin ◽  
Bacteriocin Gene

ABSTRACT Bacteriocin production is an important probiotic trait of intestinal bacteria. In this study, we identify a new type of bacteriocin, bactofencin A, produced by a porcine intestinal isolate Lactobacillus salivarius DPC6502, and assess its potency against pathogenic species including Staphylococcus aureus and Listeria monocytogenes. Genome sequencing of the bacteriocin producer revealed bfnA, which encodes the mature and highly basic (pI 10.59), 22-amino-acid defensin-like peptide. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectral analysis determined that bactofencin A has a molecular mass of 2,782 Da and contains two cysteine residues that form an intramolecular disulfide bond. Although an ABC transporter and transport accessory protein were also present within the bacteriocin gene cluster, a classical bacteriocin immunity gene was not detected. Interestingly, a dltB homologue was identified downstream of bfnA. DltB is usually encoded within the dlt operon of many Gram-positive bacteria. It is responsible for d-alanylation of teichoic acids in the cell wall and has previously been associated with bacterial resistance to cationic antimicrobial peptides. Heterologous expression of this gene conferred bactofencin A-specific immunity on sensitive strains of L. salivarius and S. aureus (although not L. monocytogenes), establishing its role in bacteriocin immunity. An analysis of the distribution of bfnA revealed that it was present in four additional isolates derived from porcine origin and absent from five human isolates, suggesting that its distribution is host specific. Given its novelty, we anticipate that bactofencin A represents the prototype of a new class of bacteriocins characterized as being cationic, with a DltB homologue providing a cognate immunity function. IMPORTANCE This study describes the identification, purification, and characterization of bactofencin A, a novel type of bacteriocin produced by L. salivarius DPC6502. Interestingly, bactofencin A is not similar to any other known bacteriocin but instead shares similarity with eukaryotic cationic antimicrobial peptides, and here, we demonstrate that it inhibits two medically significant pathogens. Genome sequence analysis of the producing strain also revealed the presence of an atypical dltB homologue in the bacteriocin gene cluster, which was lacking a classical bacteriocin immunity gene. Furthermore, cloning this gene rendered sensitive strains resistant to the bacteriocin, thereby establishing its role in providing cognate bacteriocin immunity. Four additional L. salivarius isolates, also of porcine origin, were found to contain the bacteriocin biosynthesis genes and successfully produced bactofencin A, while these genes were absent from five human-derived strains investigated.

Bacterial resistance to cationic antimicrobial peptides

2012 ◽  
Vol 39 (2) ◽  
pp. 180-195 ◽  
Author(s):  
José Luis Anaya-López ◽  
Joel Edmundo López-Meza ◽  
Alejandra Ochoa-Zarzosa
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Cationic Antimicrobial Peptides

scholarly journals Phase-Variable Expression oflptAModulates the Resistance of Neisseria gonorrhoeae to Cationic Antimicrobial Peptides

2014 ◽  
Vol 58 (7) ◽  
pp. 4230-4233 ◽  
Author(s):  
Justin L. Kandler ◽  
Sandeep J. Joseph ◽  
Jacqueline T. Balthazar ◽  
Vijaya Dhulipala ◽  
Timothy D. Read ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Antimicrobial Peptides ◽  
High Frequency ◽  
Lipid A ◽  
Bacterial Resistance ◽  
Phase Variable ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Variable Expression

ABSTRACTPhosphoethanolamine (PEA) decoration of lipid A produced byNeisseria gonorrhoeaehas been linked to bacterial resistance to cationic antimicrobial peptides/proteins (CAMPs) andin vivofitness during experimental infection. We now report that thelptAgene, which encodes the PEA transferase responsible for this decoration, is in an operon and that high-frequency mutation in a polynucleotide repeat withinlptAcan influence gonococcal resistance to CAMPs.

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

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.

Membrane targeting cationic antimicrobial peptides

2019 ◽  
Vol 537 ◽  
pp. 163-185 ◽  
Author(s):  
Daniela Ciumac ◽  
Haoning Gong ◽  
Xuzhi Hu ◽  
Jian Ren Lu
Keyword(s):  
Antimicrobial Peptides ◽  
Membrane Targeting ◽  
Cationic Antimicrobial Peptides

Cationic Antimicrobial Peptides in Penaeid Shrimp

2011 ◽  
Vol 13 (4) ◽  
pp. 639-657 ◽  
Author(s):  
Anchalee Tassanakajon ◽  
Piti Amparyup ◽  
Kunlaya Somboonwiwat ◽  
Premruethai Supungul
Keyword(s):  
Antimicrobial Peptides ◽  
Penaeid Shrimp ◽  
Cationic Antimicrobial Peptides

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

2011 ◽  
Vol 10 (1) ◽  
pp. 11 ◽  
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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