共查询到20条相似文献,搜索用时 31 毫秒
1.
Cationic host defence peptides: Innate immune regulatory peptides as a novel approach for treating infections 总被引:9,自引:0,他引:9
An increase in antibiotic resistance and the emergence of new pathogens has led to an urgent need for alternative approaches
to infection management. Immunomodulatory molecules that do not target the pathogen directly, but rather selectively enhance
and/or alter host defence mechanisms, are attractive candidates for therapeutic development. Natural cationic host defence
peptides represent lead molecules that boost innate immune responses and selectively modulate pathogen-induced inflammatory
responses. This review discusses recent evidence exploring the mechanisms of cationic host defence peptides as innate immune
regulators, their role in the interface of innate and adaptive immunity, and their potential application as beneficial therapeutics
in overcoming infectious diseases.
Received 3 November 2006; received after revision 14 December 2006; accepted 22 January 2007 相似文献
2.
Antifungal proteins: targets,mechanisms and prospective applications 总被引:15,自引:2,他引:13
All organisms have evolved several defence systems in order to protect themselves against bacteria, fungi and viruses. Higher organisms have developed a complex network of humoral and cellular responses, called adaptive immunity. A second defence system, innate immunity, was discovered in the early 1980s, consisting of small cationic peptides with a broad antimicrobial spectrum. These proteins act immediately at sites of infection or inflammation. The production of proteins with antimicrobial activity was not limited to higher organisms but was also found in insects, plants and microorganisms. During the last 2decades a broad range of proteins with very different structural features have been isolated and characterised from differing organisms ranging from bacteria to human beings. Over 500cationic membrane-acting proteins with antimicrobial and antifungal activities have been identified to date. Apart from these proteins, a very large number of antifungal proteins active on the fungal cell wall, on enzymes of the cell wall synthesis machinery, the plasma membrane and on intracellular targets have been characterised.Received 17 June 2003; received after revision 4 August 2003; accepted 18 August 2003 相似文献
3.
Temporins, anti-infective peptides with expanding properties 总被引:2,自引:1,他引:1
Mangoni ML 《Cellular and molecular life sciences : CMLS》2006,63(9):1060-1069
Antimicrobial peptides are effector molecules of the innate immune response of all pluricellular organisms, providing them
with first-line defence against pathogens. Amphibian skin secretions represent one of the richest natural sources for such
peptide antibiotics, and temporins, a large family of antimicrobial peptides from frog skin, are among the smallest ones found
in nature to date. Their functional role and modes of action have been described, along with their interesting and unique
properties. These properties make temporins good molecules for an in-depth understanding of host defence peptides in general.
Furthermore, they are attractive templates for the future design of new therapeutics against infectious diseases with new
modes of action, urgently needed due to the increasing resistance of microorganisms to the available drugs.
Received 8 November 2005; received after revision 19 December 2005; accepted 18 January 2006 相似文献
4.
Conlon JM 《Cellular and molecular life sciences : CMLS》2011,68(13):2303-2315
Cationic peptides that adopt an amphipathic α-helical conformation in a membrane-mimetic environment are synthesized in the
skins of many frog species. These peptides often display cytolytic activities against bacteria and fungi consistent with the
idea that they play a role in the host’s system of defense against pathogenic microorganisms, but their importance in the
survival strategy of the animal is not clearly understood. Despite the common misconception that antimicrobial peptides are
synthesized in the skins of all anurans, the species distribution is sporadic, suggesting that their production may confer
some evolutionary advantage to the organism but is not necessary for survival. The low potency of many frog skin antimicrobial
peptides is consistent with the hypothesis that cutaneous symbiotic bacteria may provide the major system of defense against
pathogenic microorganisms in the environment with antimicrobial peptides assuming a supplementary role in some species. 相似文献
5.
Cathelicidins - a family of multifunctional antimicrobial peptides 总被引:12,自引:0,他引:12
One component of host defence at mucosal surfaces are epithelial-derived antimicrobial peptides. Cathelicidins are one family of antimicrobial peptides characterized by conserved pro-peptide sequences that have been identified in several mammalian species. LL-37/hCAP-18 is the only cathelicidin found in humans and is expressed in inflammatory and epithelial cells. Besides their direct antimicrobial function, cathelicidins have multiple roles as mediators of inflammation influencing diverse processes such as cell proliferation and migration, immune modulation, wound healing, angiogenesis and the release of cytokines and histamine. Finally, cathelicidin antimicrobial peptides qualify as prototypes of innovative drugs that may be used to treat infection and/or modulate the immune response. This review provides an overview of antimicrobial peptides of the cathelicidin family, the structures of their genes and peptides and their biological functions. 相似文献
6.
In the last decade intensive research has been conducted to determine the role of innate immunity host defense peptides (also termed antimicrobial peptides) in the killing of prokaryotic and eukaryotic cells. Many antimicrobial peptides damage the cellular membrane as part of their killing mechanism. However, it is not clear what makes cancer cells more susceptible to some of these peptides, and what the molecular mechanisms underlying these activities are. Two general mechanisms were suggested: (i) plasma membrane disruption via micellization or pore formation, and (ii) induction of apoptosis via mitochondrial membrane disruption. To be clinically used, these peptides need to combine high and specific anticancer activity with stability in serum. Although so far very limited, new studies have paved the way for promising anticancer host defense peptides with a new mode of action and with a broad spectrum of anticancer activity. 相似文献
7.
Tollin M Bergsson G Kai-Larsen Y Lengqvist J Sjövall J Griffiths W Skúladóttir GV Haraldsson A Jörnvall H Gudmundsson GH Agerberth B 《Cellular and molecular life sciences : CMLS》2005,62(19-20):2390-2399
Vernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection. 相似文献
8.
The eye and its associated tissues including the lacrimal system and lids have evolved several defence mechanisms to prevent
microbial invasion. Included among this armory are several host-defence peptides. These multifunctional molecules are being
studied not only for their endogenous antimicrobial properties but also for their potential therapeutic effects. Here the
current knowledge of host-defence peptide expression in the eye will be summarised. The role of these peptides in eye disease
will be discussed with the primary focus being on infectious keratitis, inflammatory conditions including dry eye and wound
healing. Finally the potential of using host-defence peptides and their mimetics/derivatives for the treatment and prevention
of eye diseases is addressed. 相似文献
9.
Nicole L. van der Weerden Mark R. Bleackley Marilyn A. Anderson 《Cellular and molecular life sciences : CMLS》2013,70(19):3545-3570
Antimicrobial peptides are a vital component of the innate immune system of all eukaryotic organisms and many of these peptides have potent antifungal activity. They have potential application in the control of fungal pathogens that are a serious threat to both human health and food security. Development of antifungal peptides as therapeutics requires an understanding of their mechanism of action on fungal cells. To date, most research on antimicrobial peptides has focused on their activity against bacteria. Several antimicrobial peptides specifically target fungal cells and are not active against bacteria. Others with broader specificity often have different mechanisms of action against bacteria and fungi. This review focuses on the mechanism of action of naturally occurring antifungal peptides from a diverse range of sources including plants, mammals, amphibians, insects, crabs, spiders, and fungi. While antimicrobial peptides were originally proposed to act via membrane permeabilization, the mechanism of antifungal activity for these peptides is generally more complex and often involves entry of the peptide into the cell. 相似文献
10.
Amy A. Baxter Fung T. Lay Ivan K. H. Poon Marc Kvansakul Mark D. Hulett 《Cellular and molecular life sciences : CMLS》2017,74(20):3809-3825
There is an ongoing need for effective and targeted cancer treatments that can overcome the detrimental side effects presented by current treatment options. One class of novel anticancer molecules with therapeutic potential currently under investigation are cationic antimicrobial peptides (CAPs). CAPs are small innate immunity peptides found ubiquitously throughout nature that are typically membrane-active against a wide range of pathogenic microbes. A number of CAPs can also target mammalian cells and often display selective activity towards tumor cells, making them attractive candidates as novel anticancer agents warranting further investigation. This current and comprehensive review describes key examples of naturally occurring membrane-targeting CAPs and their modified derivatives that have demonstrated anticancer activity, across multiple species of origin and structural subfamilies. In addition, we address recent advances made in the field and the ongoing challenges faced in translating experimental findings into clinically relevant treatments. 相似文献
11.
Proline-rich antimicrobial peptides are a group of cationic host defense peptides of vertebrates and invertebrates characterized
by a high content of proline residues, often associated with arginine residues in repeated motifs. Those isolated from some
mammalian and insect species, although not evolutionarily related, use a similar mechanism to selectively kill Gram-negative
bacteria, with a low toxicity to animals. Unlike other types of antimicrobial peptides, their mode of action does not involve
the lysis of bacterial membranes but entails penetration into susceptible cells, where they then act intracellularly. Some
aspects of the transport system and cytoplasmic targets have been elucidated. These features make them attractive both as
anti-infective lead compounds and as a new class of potential cell-penetrating peptides capable of internalising membrane-impermeant
drugs into both bacterial and eukaryotic cells 相似文献
12.
Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically
valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these
problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the
basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric
(dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some
of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for
the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic
oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug
market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens. 相似文献
13.
Due to the rapid emergence of resistant microbes to the currently available antibiotics, cationic antimicrobial peptides have
attracted considerable interest as a possible new generation of anti-infective compounds. However, low cost development for
therapeutic or industrial purposes requires, among other properties, that the peptides will be small and with simple structure.
Therefore, considerable research has been devoted to optimizing peptide length combined with a simple design. This review
focuses on the similarities and differences in the mode of action and target cell specificity of two families of small peptides:
the naturally occurring temporins from the skin of amphibia and the engineered ultrashort lipopeptides. We will also discuss
the finding that acylation of cationic peptides results in molecules with a more potent spectrum of activity and a higher
resistance to proteolytic degradation. Conjugation of fatty acids to linear native peptide sequences is a powerful strategy
to engineer novel successful anti-infective drugs. 相似文献
14.
Thomas M. A. Shafee Fung T. Lay Thanh Kha Phan Marilyn A. Anderson Mark D. Hulett 《Cellular and molecular life sciences : CMLS》2017,74(4):663-682
Defensins are a well-characterised group of small, disulphide-rich, cationic peptides that are produced by essentially all eukaryotes and are highly diverse in their sequences and structures. Most display broad range antimicrobial activity at low micromolar concentrations, whereas others have other diverse roles, including cell signalling (e.g. immune cell recruitment, self/non-self-recognition), ion channel perturbation, toxic functions, and enzyme inhibition. The defensins consist of two superfamilies, each derived from an independent evolutionary origin, which have subsequently undergone extensive divergent evolution in their sequence, structure and function. Referred to as the cis- and trans-defensin superfamilies, they are classified based on their secondary structure orientation, cysteine motifs and disulphide bond connectivities, tertiary structure similarities and precursor gene sequence. The utility of displaying loops on a stable, compact, disulphide-rich core has been exploited by evolution on multiple occasions. The defensin superfamilies represent a case where the ensuing convergent evolution of sequence, structure and function has been particularly extreme. Here, we discuss the extent, causes and significance of these convergent features, drawing examples from across the eukaryotes. 相似文献
15.
In recent years the interest in antimicrobial proteins and peptides and their mode of action has been rapidly increasing due
to their potential to prevent and combat microbial infections in all areas of life. A detailed knowledge about the function
of such proteins is the most important requirement to consider them for future application. Our research in recent years has
been focused on the low molecular weight, cysteine-rich and cationic antifungal protein PAF from Penicillium chrysogenum, which inhibits the growth of opportunistic zoo-pathogens including Aspergillus fumigatus, numerous plant-pathogenic fungi and the model organism Aspergillus nidulans. So far, the experimental results indicate that PAF elicits hyperpolarization of the plasma membrane and the activation of
ion channels, followed by an increase in reactive oxygen species in the cell and the induction of an apoptosis-like phenotype.
Detailed knowledge about the molecular mechanism of action of antifungal proteins such as PAF contributes to the development
of new antimicrobial strategies that are urgently needed.
Received 09 August 2007; received after revision 17 September 2007; accepted 19 September 2007 相似文献
16.
Nelson Gomes de Oliveira Junior Marlon Henrique e Silva Cardoso Octavio Luiz Franco 《Cellular and molecular life sciences : CMLS》2013,70(24):4645-4658
Gram-positive and -negative bacteria are dangerous pathogens that may cause human infection diseases, especially due to the increasingly high prevalence of antibiotic resistance, which is becoming one of the most alarming clinical problems. In the search for novel antimicrobial compounds, snake venoms represent a rich source for such compounds, which are produced by specialized glands in the snake’s jawbone. Several venom compounds have been used for antimicrobial effects. Among them are phospholipases A2, which hydrolyze phospholipids and could act on bacterial cell surfaces. Moreover, metalloproteinases and l-amino acid oxidases, which represent important enzyme classes with antimicrobial properties, are investigated in this study. Finally, antimicrobial peptides from multiple classes are also found in snake venoms and will be mentioned. All these molecules have demonstrated an interesting alternative for controlling microorganisms that are resistant to conventional antibiotics, contributing in medicine due to their differential mechanisms of action and versatility. In this review, snake venom antimicrobial compounds will be focused on, including their enormous biotechnological applications for drug development. 相似文献
17.
Antimicrobial and cytolytic peptides of venomous arthropods 总被引:1,自引:1,他引:0
Kuhn-Nentwig L 《Cellular and molecular life sciences : CMLS》2003,60(12):2651-2668
As a response to invading microorganisms, the innate immune system of arthropods has evolved a complex arrangement of constitutive and inducible antimicrobial peptides that immediately destroy a large variety of pathogens. At the same time, venomous arthropods have developed an additional offensive system in their venom glands to subdue their prey items. In this complex venom system, several enzymes, low-molecular-mass compounds, neurotoxins, antimicrobial and cytolytic peptides interact together, resulting in extremely rapid immobilization and/or killing of prey or aggressors. This review provides an overview of antimicrobial peptides identified in the hemolymph of venomous arthropods, and especially of cytolytic peptides in their venom. For these peptides a dual role is proposed: acting as antimicrobials as well as increasing the potency of the venom by influencing excitable cells.Received 17 March 2003; received after revision 11 June 2003; accepted 17 June 2003 相似文献
18.
Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance. 相似文献
19.
Penaeidins, a family of antimicrobial peptides from penaeid shrimp (Crustacea, Decapoda) 总被引:13,自引:0,他引:13
Destoumieux D Munoz M Bulet P Bachère E 《Cellular and molecular life sciences : CMLS》2000,57(8-9):1260-1271
The production of antimicrobial peptides represents a first-line host defense mechanism of innate immunity that is widespread
in nature. Only recently such effectors were isolated in crustacean species, whereas numerous antimicrobial peptides have
been characterized from other arthropods, both insects and chelicerates. This review presents findings on a family of antimicrobial
peptides, named penaeidins, isolated from the shrimp Penaeus vannamei. Their structure and antimicrobial properties as well as their immune function will be discussed through analyses of penaeidin
gene expression and peptide distribution upon microbial challenge.
Received 21 January 2000; received after revision 10 March 2000; accepted 10 March 2000 相似文献
20.
Gramicidin S and polymyxins are small cationic cyclic peptides and act as potent antibiotics against Gram-negative and Gram-positive bacteria by perturbing integrity of the bacterial membranes. Screening of a natural antibiotics library with bacterial membrane vesicles identified gramicidin S as an inhibitor of cytochrome bd quinol oxidase and an alternative NADH dehydrogenase (NDH-2) and polymyxin B as an inhibitor of NDH-2 and malate: quinone oxidoreductase. Our studies showed that cationic cyclic peptide antibiotics have novel molecular targets in the membrane and interfere ligand binding on the hydrophobic surface of enzymes. Improvement of the toxicity and optimization of the structures and clinical uses are urgently needed for their effective application in combating drug-resistant bacteria. 相似文献