beverage industry analysis

1
Type in Product Names, Product Numbers, or CAS
Numbers to see suggestions.
NL
EN
Applications
Products
Services
Support
Login / Sign Up
Quick Order
Cart 0
Home Bacteriology Antimicrobial Peptides
Antimicrobial Peptides Chloe McClanahan
With bacterial resistance and emerging infectious
diseases becoming potential threats to humans,
ribosomally synthesized antimicrobial peptides
have become a promising focus area in antibiotic
research. Antimicrobial peptides are classiked as
either non-ribosomally synthesized peptides or
ribosomally synthesized peptides (RAMPs).
Non-ribosomally synthesized peptides are found in
bacteria and fungi. These antimicrobial peptides
are assembled by peptide synthetases as opposed
to ribosomal-supported synthesis. Gramicidin,
bacitracin, polymyxin B, and vancomycin are
examples of non-ribosomally synthesized
antimicrobial peptides. These antibiotics are
proven to be effective research tools, but
compared to RAMPs they are disadvantageous for
novel applications due to emerging bacterial
resistance, for example vancomycin-resistant
Staphylococcus aureus and enterococci.
RELATED ARTICLES
Cell Culture Contamination Troubleshooting Strept
ococci - Overview of Detection, Identihcation,
Differentiation and Inhibition of Cell Wall
Biosynthesis by Antibiotics Lactobacilli Overview
of Chromogenic Media Media for Staphylococcus
Aureus Detection Ready-to-Use Staining Kits and
Solutions for Bacteriologic Differentiation of
Escherichia coli from coliforms
RAMPs are derived from a diverse range of
species, from prokaryotes to humans.
Antimicrobial peptides comprise a hosts natural
defense against the daily exposure to millions
of potential pathogens. These peptides may also
possess antiviral, antiparasitic, and
antineoplastic activities. Over 500 RAMPs have
been described in the literature. Their unique
antibiotic spectrum is determined by amino acid
sequence and structural conformation. RAMPs are
gene-encoded peptides consisting of 12-50 amino
acids with very little genetic overlap. A lack of
sequence homology between RAMPs is indicative of
evolutionary optimization of form and function in
the species environment. RAMPs are typically
cationic peptides with at least half of the amino
acid residues being hydrophobic and a smaller
number of neutral or negatively charged
residues. Their amphipathic structure with
opposing hydrophobic and lipohphilic faces aids
in the perturbation of the bacterial cell wall.
The mechanism of action of a RAMP involves
peptide binding to the bacterial cell surface,
conformational change to the peptide,
aggregation of multiple peptide monomers, and
pore formation through the bacterial cell wall.
RAMPs bind to lipopolysaccharides in the
negatively-charged, Gram-negative bacterial outer
cell wall or to the acidic polysaccharides of the
Gram-positive bacterial outer cell wall. After
binding, permeabilization of the bilayer membrane
occurs by transient pore creation.
Permeabilization leads to a leakage of cell
components and cell death. There are several
models of permeabilization although the precise
mechanism is unknown. Three permeabilization
models are termed barrel-stave, thoroidal, and
carpet. Figure 1. depicts bacterial cell wall
perturbation by a RAMP.
RELATED PRODUCT CATEGORIES Antibiotics

• Figure 1. Antimicrobial peptide perturbation of
  the bacterial cell wall via the carpet model
  mode of action.
• RAMPs are ideal candidates for clinical
  antimicrobial use because they
• Are active against antibiotic-resistant isolates
• Do not select for resistant mutants and have
  limited natural bacterial resistance
• Are synergistic with conventional antibiotics,
  specikcally against resistant mutants
• Are proven to kill bacteria in animal models
• Kill rapidly
• Provide benekcal, supplementary activities, for
  example sepsis inhibition
• Although RAMPs are ideal clinical candidates,
  their diverse structural variation makes it
  difkcult to predict RAMP activity in vivo
  therefore, it is challenging to design
  functional synthetic mimetics. Small changes in
  peptide sequence or conformation can lead to
  major in vivo differences in antimicrobial and
  cytotoxicity levels. An optimal in vitro minimum
  inhibitory concentration (MIC) against a range of
  bacterial organisms is 18 µg/mL. However, it is
  challenging to predict an ideal in vivo MIC from
  this in vitro MIC. In order to obtain MIC,
  specikcity, stability and toxicity information,
  novel, synthetic antimicrobial peptides have been
  designed using data from RAMP-related,
  bioinformatic databases (Table 1). Production
  costs, protease susceptibility, and potential
  resistance from widespread use are additional
  concerns in the transition of RAMP application
  from a research to clinical setting.

Antimicrobial Peptide Databases Information
Available Web Site
BAGEL
http//bioinformatics.biol.rug.nl/websoftware/
2
Molecular Genetics Dept., University of
Groningen, The Netherlands
Bacteriocin genome location tool.
bagel/bagel_start.php
PhytAMP ISSBAT Institute, Tunisia and INAF
Institute, Laval University, Canada
Structural information and phylogenetic tree for
270 natural, plant antimicrobial peptides.
http//phytamp.pfba-lab-tun.org/main.php
Antimicrobial Peptide Database, Version 2 UNMC
Eppley Cancer Center, University of Nebraska
Medical Center, USA
Structural and functional information for 1,000
antibacterial peptides.
http//aps.unmc.edu/AP/main
SAPD Haartman Institute, Helsinki University,
Finland
Synthetic antibiotic peptide database.
http//oma.terkko.helsinki.k8080/SAPD
Defensins Knowledgebase Bioinformatics
Institute, Singapore and Singapore Eye Research
Institute
Sequence, structural and activity information
for 360 defensins.
http//defensins.bii.a-star.edu.sg/
Table 1 Antimicrobial Peptide Online
Databases BACTERIOCINS Bacteriocins are
non-pathogenic, antimicrobial peptides or
proteins secreted by both Gram-positive and
Gram-negative bacteria. Bacteriocins prevent the
growth of similar bacterial strains but avoid
damaging the host bacteria by selectively killing
based on post- transcriptional modikcation
and/or specikc immunity mechanisms. Unlike the
wide activity spectrum of conventional
antibiotics, bacteriocins have a narrow activity
spectrum. Additionally bacteriocins play a role
in the regulation of signaling, virulence, and
sporulation. Nisin (Cat. No. N5764) is classiked
as a Class I, Type A lantibiotic. It is produced
by Gram-positive, lactic acid fermentation
bacteria and contains several atypical modiked
amino acids thioetherbridged lanthionine,
methyllanthionine, didehydroalanine and
didehydroaminobutyric acid. Class I, Type A
lantibiotics are elongated peptides that exhibit
a range of activities including pore formation in
bacterial bilayers while Class I, Type B
lantibiotics are smaller, globular negatively
charged or neutral peptides that inhibit specikc
enzymes. Class I, Type B lantibiotics include
cinnamycin (Cat. No. C5241) and duramycin (Cat.
No. D3168). An interesting subgroup of the non-
lantibiotic bacteriocins is the Class IIa
pediocin-like peptides. Pediocin (Cat. No. P0098)
has been studied for its activity against
pathogenic bacteria such as Listeria
monocytogenes. Although the genetic sequences of
bacteriocins are not conserved, bacteriocin genes
are often positioned near genes that aid in their
production, for example transporter genes. BAGEL
is a bacteriocin genome location tool developed
and maintained by the Molecular Genetics
Department at the University of Groningen, The
Netherlands. This software is available for both
academic and commercial use at
http//bioinformatics.biol.rug.nl/websoftware/bage
l/bagel_start.php. Many of the bacteriocins are
being studied for their application in food
preservation. This methodology reduces
requirements for potentially carcinogenic
pesticides and heat treatments that reduce
nutritional properties in food. Bacteriocins may
function as alternatives to conventional
antibiotics that have been impacted by resistant
strains. Millette, M. et al. recently
demonstrated that nisin- and pediocin-producing
bacteria reduced intestinal colonization by
vancomycin-resistant Enterococci in
vivo. INSECT RAMPS Cecropin is a type of RAMP
secreted within insects and active against
Gram-negative bacteria. Cecropin A (Cat. No.
C6830) is extracted from the hemolymph of the
silk moth (Hyalophora cecropia) but has also been
identiked in porcine intestine. Antimicrobial
peptides are often components of insect venoms,
for example melittin from bee venom (Cat. No.
M2272). It has been proposed that in primitive
insect species RAMPs replace immune system
processes, for example cytokine release, that
characterize the bactericidal response in higher
organisms. Drosophila synthesize different
antimicrobial peptides in response to various
infecting organisms. Kallio, J. et al. reported
that RNAi targeting of several immune response
genes in Drosophila caused altered antimicrobial
peptide synthesis and identiked involvement of
the JNK signaling pathway in RAMP
production. MAMMALIAN RAMPS Although
bacteriocins, insect, and mammalian RAMPs are
similar in their bactericidal activity, the
mammalian RAMPs also function as regulatory
molecules in the host species immune
response. Defensins are a group of cationic,
mammalian RAMPs that are commonly found on the
skin, ear, epithelium, tongue, lung, and other
surfaces frequently exposed to environmental
pathogens. Phagocytic and epithelial cells,
lymphocytes, and keratinocytes produce defensins.
Figure 2 is an immunohistochemical staining of
defensin-5 within respiratory epithelial cells
using Prestige Antibodies Anti-DEFA5 antibody,
produced in rabbit (Cat. No. HPA015775).
Defensins are constitutively expressed and stored
in granules without external stimuli. However,
increased levels of expression may be induced by
proinflammatory cytokines, exogenous bacterial or
LPS treatment.
3
Figure 2. Immunohistochemical staining of human
nasopharynx shows cytoplasmic and membranous
positivity in respiratory epithelial cells using
Prestige Antibodies Anti-DEFA5 (Cat. No.
HPA015775). Like the bacteriocins, defensins
consist of variable amino acid residue
composition. The two classes of defensins are
dekned by structure. The human a-defensins have
three intramolecular cysteine bonds whereas the
larger ß-defensins (Cat. Nos. D9565, ß-defensin 1
and D9690, ß-defensin 2) consist of three
antiparallel ß-sheets and a unique disulkde
bridge pattern connecting six cysteine residues.
In addition to antimicrobial and antiviral
activities, a-defensins inactivate LPS binding,
regulate complement activation, and function as
an adjuvant in mice. ß-defensins induce
prostaglandin production and play a regulatory
role in the adaptive immune responses by
functioning as chemoattractants for T lymphocytes
as well as for immature dendritic cells via
signaling through a chemokine receptor.
Materials
Product Number
Product Description
SDS
Cecropin A 97 (HPLC), powder
C6830
Pricing
Cinnamycin
C5241
Pricing
from Streptomyces cinnamoneus, 95 (HPLC)
HPA015775 Anti-DEFA5 antibody produced in rabbit Prestige Antibodies Powered by Atlas Antibodies, afknity isolated Pricing
antibody, buffered aqueous glycerol solution
ß-Defensin 1 human
D9565 98 (HPLC and SDS-PAGE), recombinant, expressed in E. coli, Pricing
lyophilized powder (from 10 mM acetic acid)
ß-Defensin 2 human
D9690 recombinant, expressed in E. coli, lyophilized powder (from 10 mM Pricing
acetic acid)
Duramycin from Streptoverticillium
cinnamoneus 90.0
D3168
Pricing
Melittin from honey bee venom 85 (HPLC)
M2272
Pricing
Nisin from Lactococcus lactis 2.5 (balance
sodium chloride)
N5764
Pricing
Pediocin from Pediococcus acidilactici 95
(HPLC), buffered aqueous solution
P0098
Pricing

• References
• Pag U. In vitro activity and mode of action of
  diastereomeric antimicrobial peptides against
  bacterial clinical isolates. Journal of
  Antimicrobial Chemotherapy. 53(2)230-239.
  http//d x.doi.org/10.1093/jac/dkh083
• Papagianni M. 2003. Ribosomally synthesized
  peptides with antimicrobial properties
  biosynthesis, structure, function, and
  applications. Biotechnology Advances.
  21(6)465-499. h ttp//dx.doi.org/10.1016/s0734-9
  750(03)00077-6
• Gunn J. 2001. Bacterial modikcation of LPS and
  resistance to antimicrobial peptides. J.
  Endotoxin Res.. 7(1)57-62. http//dx.doi.org/10.1
  179/096805101101532558
• Nicholson JK, Holmes E, Lindon JC, Wilson ID.
  2004. The challenges of modeling mammalian
  biocomplexity. Nat Biotechnol. 22(10)1268-1274.
  http//dx.doi.org/10.1038/nbt101 5
• Pálffy R, Gardlík R, Behuliak M, Kadasi L, Turna
  J, Celec P. 2009. On the Physiology and
  Pathophysiology of Antimicrobial Peptides. Mol
  Med. 15(1-2)51-59. http//dx.doi.org/10.21
  19/molmed.2008.00087
• Hancock REW, Chapple DS. 1999. Peptide
  Antibiotics. Antimicrob. Agents Chemother..
  43(6)1317-1323. http//dx.doi.org/10.1128/aac.43.
  6.1317
• Hancock REW, Scott MG. 2000. The role of
  antimicrobial peptides in animal defenses.
  Proceedings of the National Academy of Sciences.
  97(16)8856-8861. http//dx.doi.org/10.10
  73/pnas.97.16.8856
• Drider D, Fimland G, He?chard Y, McMullen LM,
  Pre?vost H. 2006. The Continuing Story of Class
  IIa Bacteriocins. MMBR. 70(2)564-582.
  http//dx.doi.org/10.1128/mmbr.00016- 05
• Holtsmark I, Eijsink VG, Brurberg MB. 2008.
  Bacteriocins from plantpathogenic bacteria.
  280(1)1-7. http//dx.doi.org/10.1111/j.1574-6968.
  2007.01010.x

4

1. and HC, Hoover D. 2003. Bacteriocins and their
   Food Applications. Comp Rev Food Sci Food Safety.
   2(3)82-100. http//dx.doi.org/10.1111/j.1541-4337
   .2003.tb00016.x
2. Gálvez A, López RL, Abriouel H, Valdivia E, Omar
   NB. 2008. Application of Bacteriocins in the
   Control of Foodborne Pathogenic and Spoilage
   Bacteria. Critical Reviews in Biotechnology.
   28(2)125-152. http//dx.doi.org/10.1080/073885508
   02107202
3. Gálvez A, Abriouel H, López RL, Omar NB. 2007.
   Bacteriocin-based strategies for food
   biopreservation. International Journal of Food
   Microbiology. 120(1-2)51-70. http//dx.doi.
   org/10.1016/j.ijfoodmicro.2007.06.001
4. Brumktt W. 2002. Nisin, alone and combined with
   peptidoglycan-modulating antibiotics activity
   against methicillin-resistant Staphylococcus
   aureus and vancomycin-resistant enterococci.
   50(5)731-734. http//dx.doi.org/10.1093/jac/dkf19
   0
5. Millette M, Cornut G, Dupont C, Shareck F,
   Archambault D, Lacroix M. 2008. Capacity of Human
   Nisin- and Pediocin-Producing Lactic Acid
   Bacteria To Reduce Intestinal Colonization by
   Vancomycin-Resistant Enterococci. AEM.
   74(7)1997-2003. http//dx.doi.org/10.1128/aem.021
   50-07
6. Montesinos E. 2007. Antimicrobial peptides and
   plant disease control. 270(1)1-11.
   http//dx.doi.org/10.1111/j.1574-6968.2007.00683.x
   
7. Buckling A, Brockhurst M. 2005. RAMP resistance.
   Nature. 438(7065)170-171. http//dx.doi.org/10.10
   38/438170a

17. Kallio J, Leinonen A, Ulvila J, Valanne S,
Ezekowitz RA, Rämet M. 2005. Functional analysis
of immune response genes in Drosophila identikes
JNK pathway as a regulator of antimicrobial
peptide gene expression in S2 cells. Microbes and
Infection. 7(5-6)811-819. http//dx.doi.org/10.10
16/j.micinf.2005.03.014 18. Komatsuzawa H,
Ouhara K, Yamada S, Fujiwara T, Sayama K,
Hashimoto K, Sugai M. 2006. Innate defences
against methicillin-resistantStaphylococcus
aureus (MRSA) infection. J. Pathol..
208(2)249-260. http//dx.doi.org/10.1002/path.189
8 19. Meade KG, Cahalane S, Narciandi F,
Cormican P, Lloyd AT, O?Farrelly C. 2008.
Directed alteration of a novel bovine ?-defensin
to improve antimicrobial efkcacy against
methicillin- resistant Staphylococcus aureus
(MRSA). International Journal of Antimicrobial
Agents. 32(5)392-397. http//dx.doi.org/10.1016/j
.ijantimicag.2008.05.005 20. Oppenheim JJ. 2003.
Roles of antimicrobial peptides such as defensins
in innate and adaptive immunity. Annals of the
Rheumatic Diseases. 62(90002)17ii-21.
http//dx.doi.org/1 0.1136/ard.62.suppl_2.ii17 21
. Yang D, Chertov O, Oppenheim JJ. 2001. The role
of mammalian antimicrobial peptides and proteins
in awakening of innate host defenses and adaptive
immunity. CMLS, Cell. Mol. Life Sci..
58(7)978-989. http//dx.doi.org/10.1007/pl0000091
4 22. Yang D, Chertov O, Bykovskaia SN, Chen Q,
Buffo MJ, Shogan J, Anderson M, Schröder JM, Wang
JM, Howard OMZ, et al. 1999. ?-Defensins Linking
Innate and Adaptive Immunity Through Dendritic
and T Cell CCR6. Science. 286(5439)525-528.
http//dx.doi.org/10.1126/science.286.5439.525
Support
Orders
Company
Social Media
Merck Research. Development. Production. We are a
leading supplier to the global Life Science
industry with solutions and services for
research, biotechnology development and
production, and pharmaceutical drug therapy
development and production.
Customer Support
Quick Order
About Us
Contact Us
Custom Products
Responsibility
FAQ
Commerce Solutions
Events
Safety Data Sheets (SDS)
Press Releases
Certihcates (COA/COO)
Programs
Quality Regulatory
Careers
Calculators Apps
Ofhces
Webinars
Sigma-Aldrich Solutions
BioReliance Solutions
Millipore Solutions
SAFC Solutions
Milli-Q Solutions
Supelco Solutions
2021 Merck KGaA, Darmstadt, Germany and/or its
afhliates. All Rights Reserved. Reproduction of
any materials from the site is strictly forbidden
without permission. Site Use Terms Privacy
Policy General Terms and Conditions of Sale
Copyright Consent