Antimicrobial effects of α-MSH peptides

Cutuli, Mariagrazia; Cristiani, Silvia; Lipton, James M.; Catania, Anna

doi:10.1002/jlb.67.2.233

Cited by 141 publications

(170 citation statements)

References 28 publications

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“…Our study also demonstrated that ␣-MSH damages the S. aureus membrane in a dose dependent manner (31). Studies by others have revealed that the candidacidal effect of ␣-MSH might be mediated through the induction of cyclic AMP (cAMP) (12). In addition, an analogue of ␣-MSH is already being studied in clinical trials to treat candidial vaginitis (18).…”

supporting

confidence: 62%

“…Several reports, including ours, have recently demonstrated that ␣-MSH and its C-terminal sequence [Lys-Pro-Val, i.e., ␣-MSH(11-13)] have strong and rapid antimicrobial activity against methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), Escherichia coli, and Candida albicans (10,12,31). In our previous study we showed that ␣-MSH is active against staphylococcal biofilm and can retain its activity in whole blood, plasma, and serum (31).…”

mentioning

confidence: 97%

“…␣-MSH also shares a number of similarities with other natural host defense antimicrobial peptides. For example, (i) it is cationic in nature, (ii) it adopts a helical structure in a membrane mimetic environment (32), (iii) it causes membrane permeabilization like known antimicrobial peptides (31), and (iv) it has broad spectrum of antimicrobial activity (10,12,18,31).…”

mentioning

confidence: 99%

“…In the present study, our main aim was to determine the role of the amino acid sequences, particularly the contributions of N-terminal and C-terminal regions, in the staphylocidal mechanism of ␣-MSH. We selected four sequences of ␣-MSH, i.e., the entire ␣-MSH, ␣-MSH(1-5), ␣-MSH(6-13), and ␣-MSH (11)(12)(13), and studied in detail their antistaphylococcal activities against both MSSA and MRSA strains. The study was also extended to understand the effect of NaCl and different ions (Mg 2ϩ and Ca 2ϩ ) on the killing efficacy of peptides against S. aureus.…”

mentioning

confidence: 99%

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C-Terminal Amino Acids of Alpha-Melanocyte-Stimulating Hormone Are Requisite for Its Antibacterial Activity against Staphylococcus aureus

Singh

Mukhopadhyay

2011

Antimicrob Agents Chemother

105

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Alpha-melanocyte-stimulating hormone (␣-MSH) is an endogenous neuropeptide that is known for its anti-inflammatory and antipyretic activities.We recently demonstrated that ␣-MSH possesses staphylocidal activity and causes bacterial membrane damage. To understand the role of its amino acid sequences in the staphylocidal mechanism, in the present study we investigated the antimicrobial activities of different fragments of ␣-MSH, i.e., ␣-MSH(6-13), ␣-MSH(11-13), and ␣-MSH(1-5), and compared them with that of the entire peptide. Our results showed that peptides containing the C-terminal region of ␣-MSH, namely, ␣-MSH(6-13) and ␣-MSH(11-13), efficiently killed >90% of both methicillin-sensitive and -resistant Staphylococcus aureus cells in the micromolar range and ϳ50% of these cells in the nanomolar range; their efficiency was comparable to that of the entire ␣-MSH, whereas the peptide containing the N-terminal region, ␣-MSH(1-5), was found to be ineffective against S. aureus. The antimicrobial activity of ␣-MSH and its C-terminal fragments was not affected by the presence of NaCl or even divalent cations such as Ca 2؉ and Mg 2؉ . Similar to the case for the parent peptide, ␣-MSH(6-13) and ␣-MSH(11-13) also depolarized and permeabilized Staphylococcus cells (ϳ70 to 80% of the cells were depolarized and lysed after 2 h of peptide exposure at micromolar concentrations). Furthermore, scanning and transmission electron microscopy showed remarkable morphological and ultrastructural changes on S. aureus cell surface due to exposure to ␣-MSH-based peptides. Thus, our observations indicate that C-terminal fragments of ␣-MSH retain the antimicrobial activity of entire peptide and that their mechanism of action is similar to that of full-length peptide. These observations are important and are critical in the rational design of ␣-MSH-based therapeutics with optimal efficacy.

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supporting

confidence: 62%

mentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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C-Terminal Amino Acids of Alpha-Melanocyte-Stimulating Hormone Are Requisite for Its Antibacterial Activity against Staphylococcus aureus

Singh

Mukhopadhyay

2011

Antimicrob Agents Chemother

105

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“…This unexpected finding could result from neuropeptide antibacterial activity. Recent studies showed indeed that αMSH, ghrelin, VIP and adrenomedullin act as potent antimicrobial peptides that directly kill various bacterial and yeast strains (Allaker et al, 2006;Brogden et al, 2005;Chorny and Delgado, 2008;Cutuli et al, 2000). The neuropeptides share some important characteristics with natural antimicrobial peptides, including small size (<10 kDa), high positive charge, and amphipathic α-helix structures adopted upon interaction with membranes.…”

Section: Neuropeptides As Natural Antimicrobial Peptides: a New Emergmentioning

confidence: 99%

Anti-inflammatory neuropeptides: A new class of endogenous immunoregulatory agents

Delgado

Ganea

2008

Brain, Behavior, and Immunity

105

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Resolution of inflammation and induction of immune tolerance are essential to stabilize immune homeostasis and to limit the occurrence of exacerbated inflammatory and autoimmune conditions. Multiple mechanisms act together to ensure the re-establishment of immune homeostasis and maintenance of tolerance. The identification of endogenous factors that regulate these processes is crucial for the development of new therapies for inflammatory/autoimmune conditions. Neuropeptides produced during an ongoing inflammatory response emerged as endogenous antiinflammatory agents that participate in processes leading to the resolution of inflammation and maintenance of tolerance. Anti-inflammatory neuropeptides and hormones such as vasoactive intestinal peptide, urocortin, adrenomedullin, melanocyte stimulating hormone, ghrelin and cortistatin have beneficial effects in a variety of experimental inflammatory and autoimmune models. Their therapeutic effect has been attributed to their capacity to downregulate innate immunity, to inhibit antigen-specific T H 1-driven responses, and to generate regulatory T cells. Finally, some of these neuropeptides have been identified as mediators of innate defense acting as natural antimicrobial peptides. Here we present the research findings in the neuropeptide immunoregulatory field, and examine possible therapies based on anti-inflammatory neuropeptides and hormones as a new pharmacologic platform.

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Antimicrobial Peptides: Their History, Evolution, and Functional Promiscuity

2013

Antimicrobial Peptides

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Antimicrobial effects of α-MSH peptides

Cited by 141 publications

References 28 publications

C-Terminal Amino Acids of Alpha-Melanocyte-Stimulating Hormone Are Requisite for Its Antibacterial Activity against Staphylococcus aureus

C-Terminal Amino Acids of Alpha-Melanocyte-Stimulating Hormone Are Requisite for Its Antibacterial Activity against Staphylococcus aureus

Anti-inflammatory neuropeptides: A new class of endogenous immunoregulatory agents

Antimicrobial Peptides: Their History, Evolution, and Functional Promiscuity

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