Novel antimicrobial peptides derived from human immunodeficiency virus type 1 and other lentivirus transmembrane proteins.

We have previously described a conserved set of peptides derived from lentiviral envelope transmembrane proteins that are similar to the natural antimicrobial peptides cecropins and magainins in overall structure but bear no sequence homology to them or other members of their class. We describe here an evaluation of the antimicrobial properties of these virally derived peptides, designated lentivirus lytic peptides (LLPs). The results of this study demonstrate that they are potent and selective antibacterial peptides: the prototype sequence, LLP1, is bactericidal to both gram-positive and gram-negative organisms at micromolar concentrations in 10 mM phosphate buffer. Furthermore, LLP1 kills bacteria quite rapidly, causing a 1,000-fold reduction in viable organisms within 50 s. Peptides corresponding to sequences from three lentivirus envelope proteins were synthesized and characterized. Several of these peptides are selective, killing bacteria at concentrations 50- to 100-fold lower than those required to lyse erythrocytes. Development of antimicrobial agents based on these peptides may lead to improved therapeutics for the management of a variety of infectious diseases.

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Evaluation of Antimicrobial Activity of Buforin I and Nisin and the Synergistic Effect of Their Combination as a Novel Antimicrobial Preservative

Journal of Food Protection ◽

10.4315/jfp-20-127 ◽

2020 ◽

Vol 83 (11) ◽

pp. 2018-2025 ◽

Cited By ~ 1

Author(s):

SAHAR ROSHANAK ◽

FAKHRI SHAHIDI ◽

FARIDEH TABATABAEI YAZDI ◽

ALI JAVADMANESH ◽

JEBRAEIL MOVAFFAGH

Keyword(s):

Antimicrobial Activity ◽

Synergistic Effect ◽

Antimicrobial Peptides ◽

Antimicrobial Agents ◽

Antimicrobial Properties ◽

Food Spoilage ◽

Food Preservatives ◽

Minimum Fungicidal Concentration ◽

E Coli ◽

Spoilage Microorganisms

ABSTRACT One of the most effective methods for increasing the antimicrobial activity of a substance is to combine it with one or more other antimicrobial agents. The aim of the present study was to evaluate the antimicrobial effect of buforin I and nisin alone and investigate the synergistic action of these compounds against the most important food spoilage microorganisms, including Bacillus subtilis, Staphylococcus epidermidis, Listeria innocua, Escherichia coli, Salmonella serovar Enteritidis, Aspergillus oryzae, Rhodotorula glutinis, and Geotrichum candidum. The results of MIC and MBC or minimum fungicidal concentration examinations showed that buforin I had higher antimicrobial activity than nisin on all microbial strains used in this study (P ≤ 0.5). E. coli was the most resistant to both antimicrobial agents, whereas L. innocua and S. epidermidis were the most sensitive to nisin and buforin I, respectively. The results of synergistic interaction between buforin I and nisin indicated that the combination of buforin I and nisin on B. subtilis, S. epidermidis, and A. oryzae showed a synergistic effect, whereas it had no effect on Salmonella serovar Enteritidis and G. candidum. The combination of buforin I and nisin showed a partial synergistic effect on L. innocua, E. coli, and R. glutinis. Assessment of viability of the microorganisms under the antimicrobial agents alone and in combination with each other at MICs and fraction inhibitory concentrations indicated that use of these antimicrobial agents in combination enhances antimicrobial activity at lower concentrations of both agents. The present study investigated the antimicrobial properties of buforin I against food spoilage microorganisms for the first time and suggests that its use alone or with nisin may provide a clear horizon for the application of antimicrobial peptides as natural preservatives. Thus, the combination of antimicrobial peptides and traditional antimicrobial food preservatives could be a promising option for the prevention of contamination, spoilage, and infestation of food and beverage products. HIGHLIGHTS

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Anti-Human Immunodeficiency Virus Type 1 Activities of Antimicrobial Peptides Derived from Human and Bovine Cathelicidins

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00452-08 ◽

2008 ◽

Vol 52 (9) ◽

pp. 3438-3440 ◽

Cited By ~ 60

Author(s):

Guangshun Wang ◽

Karen M. Watson ◽

Robert W. Buckheit

Keyword(s):

Human Immunodeficiency Virus ◽

Antimicrobial Peptides ◽

Human Immunodeficiency Virus Type ◽

Therapeutic Index ◽

Peptide Sequence ◽

Helical Structures ◽

Aromatic Residues ◽

Immunodeficiency Virus ◽

Hiv Inhibition

ABSTRACT From among 15 human cathelicidin LL-37-derived peptides, FK-13 was identified as the smallest peptide active against human immunodeficiency virus (HIV) and GI-20 had the highest therapeutic index, which was twice that of LL-37. BMAP-18, which is derived from bovine cathelicidin BMAP-27, possessed a therapeutic index similar to that of GI-20. Peptide sequence order, helical structures, and aromatic residues are important in HIV inhibition.

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Histatin 5-Derived Peptide with Improved Fungicidal Properties Enhances Human Immunodeficiency Virus Type 1 Replication by Promoting Viral Entry

Journal of Virology ◽

10.1128/jvi.00796-06 ◽

2006 ◽

Vol 80 (18) ◽

pp. 9236-9243 ◽

Cited By ~ 22

Author(s):

Fedde Groot ◽

Rogier W. Sanders ◽

Olivier ter Brake ◽

Kamran Nazmi ◽

Enno C. I. Veerman ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Antimicrobial Peptides ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Viral Entry ◽

Histatin 5 ◽

Immunodeficiency Virus ◽

Body Compartments ◽

Hiv 1

ABSTRACT Antimicrobial peptides are found in a number of body compartments and are secreted at mucosal surfaces, where they form part of the innate immune system. Many of these small peptides have a broad spectrum of inhibitory activity against bacteria, fungi, parasites, and viruses. Generally, the peptide's mode of action is binding and disruption of membranes due to its amphipathic properties. Histatin 5 is a salivary peptide that inhibits Candida albicans, an opportunistic fungus that causes oropharyngeal candidiasis in a majority of human immunodeficiency virus type 1 (HIV-1)-infected patients progressing towards AIDS. Previously, we increased the fungicidal properties of histatin 5 by replacing amino acids in the active domain of histatin 5 (Dh-5) (A. L. Ruissen, J. Groenink, E. J. Helmerhorst, E. Walgreen-Weterings, W. van’t Hof, E. C. Veerman, and A. V. Nieuw Amerongen, Biochem. J. 356:361-368, 2001). In the current study, we tested the anti-HIV-1 activity of Dh-5 and its derivatives. Although Dh-5 inhibited HIV-1 replication, none of the peptide variants were more effective in this respect. In contrast, one of the derivatives, Dhvar2, significantly increased HIV-1 replication by promoting the envelope-mediated cell entry process. Most likely, Dhvar2 affects membranes, thereby facilitating fusion of viral and cellular membranes. This study shows that modification of antimicrobial peptides in order to improve their activity against a pathogen may have unpredictable and unwanted side effects on other pathogens.

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Combination of mutations in human immunodeficiency virus type 1 reverse transcriptase required for resistance to the carbocyclic nucleoside 1592U89.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.5.1094 ◽

1997 ◽

Vol 41 (5) ◽

pp. 1094-1098 ◽

Cited By ~ 144

Author(s):

M Tisdale ◽

T Alnadaf ◽

D Cousens

Keyword(s):

Human Immunodeficiency Virus ◽

Reverse Transcriptase ◽

In Vitro Selection ◽

Fold Reduction ◽

Immunodeficiency Virus ◽

Rt Inhibitors ◽

Carbocyclic Nucleoside ◽

Hiv 1

The carbocyclic nucleoside 1592U89 is a selective inhibitor of the human immunodeficiency virus (HIV), targeting the reverse transcriptase (RT). In vitro selection studies were undertaken to generate resistant variants with both HIV type 1 (HIV-1) wild-type strain HIV-1(HXB2) and 3'-azido-3'-deoxythymidine (AZT)-resistant strain HIV-1(RTMC). At least two or three mutations in RT were required to produce a 10-fold reduction in susceptibility. The first RT mutation selected was at codon 184, methionine (M) to valine (V), for HIV-1(HXB2) and HIV-1(RTMC), conferring two- and fivefold resistance, respectively. Two additional mutations were selected with HIV-1(HXB2), either leucine (L) 74 to V and lysine (K) 65 to arginine (R) (first-passage series) or L74 to V and tyrosine (Y) 115 to phenylalanine (F) (second-passage series). Cloned variants, obtained from the 1592U89 selection, were either double RT mutants 65R/184V and 74V/184V or triple RT mutant 74V/115Y/184V. Molecular clones were constructed with single, double, and triple combinations of these mutations for resistance analysis with different RT inhibitors. Each individual mutation conferred only low-level resistance (two- to fourfold) to 1592U89 in the HXB2 background. Double mutants containing the 184V mutation and triple mutants showed slightly greater levels of resistance to 1592U89 (7- to 11-fold). Some of the 1592U89-resistant variants were cross-resistant with 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and (-)-2'-deoxy-3'-thiacytidine, but none were resistant to 2',3'-didehydro-3'-deoxythymidine or AZT.

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