Antimicrobial peptides from the skin of frogs may protect against life-threatening, multidrug-resistant infections such as Pseudomonas aeruginosa say researchers from Italy. They detail their findings in the September 2010 issue of the journal Antimicrobial Agents and Chemotherapy.
P. aeruginosa is an opportunistic pathogen that causes some of the most prevalent life-threatening infections such as eye and ear infections, burn wound infections and lung infections in cystic fibrosis patients. Strains of the bacterium resistant to almost all antibiotics have already emerged causing researchers to seek new drug therapies.
"Unlike other organisms, P. aeruginosa is a pathogen endowed with high intrinsic drug resistance, due in part to many elaborate virulence factors and the formation of a biofilm matrix, which makes it difficult for antibiotics and immune cells to attack," say the researchers.
Membrane-active cationic antimicrobial peptides (CAMPs) are a new class of antibiotics produced by almost all forms of life, however, amphibian skin is one of the richest sources. Although prior studies have shown that these peptides possess potent antimicrobial activity against multidrug-resistant pathogens in a controlled environment, little is known of their effects within a living organism.
Researchers evaluated the antimicrobial activities of different CAMPs from frog skin using the worm model, Caenorhabditis elegans, in which bacterial species such as P. aeruginosa can pass through the mouth, invade the gut and ultimately kill the animal. The process by which the bacterium infects and kills C. elegans is comparable to the infection process in mammals making it an ideal model for observation. Results showed that all of the peptides studied, with the exception of one, increased the survival rate of P. aeruginosa-infected worms compared with those not receiving peptide treatments.
"Besides shedding light on a plausible mode of action in vivo of amphibian CAMPs, our data suggest that esculentin and temporin peptides can serve as attractive molecules for the development of new therapeutic strategies to fight life-threatening infectious diseases," say the researchers.
(D. Uccelletti, E. Zanni, L. Marcellini, C. Palleschi, D. Barra, M.L. Mangoni. 2010. Anti-Pseudomonas activity of frog skin antimicrobial peptides in a Caenorhabditis elegans infection model: a plausible mode of action in vitro and in vivo. Antimicrobial Agents and Chemotherapy, 54. 9: 3853-3860.)
Self-Administered Vaccine Patch May Protect Against Potentially Pandemic Flu Viruses
A self-administered patch containing tiny microneedles may effectively deliver influenza virus-like particles through the skin and protect against potentially pandemic flu viruses such as H5N1. Researchers from the U.S. and abroad report their findings in the September 2010 issue of the journal Clinical Vaccine and Immunology.
In the United States, seasonal flu epidemics often result in over 200,000 hospitalizations and 36,000 deaths each year. New pandemic flu strains continue to emerge, such as the 2009 H1N1 virus that resulted in the first pandemic influenza outbreak in the 21st century. Conventional vaccination programs require a painful injection administered by medical personnel and can take months to develop, emphasizing the need for vaccines that can be rapidly produced at low cost and distributed within weeks.
Influenza virus-like particles (VLPs) are potentially promising vaccine candidates as they are non-infectious and have been shown to induce long-lasting immunity against pandemic influenza viruses. An abundance of dermal dendritic cells, important members of the skins' immune system, make the skin an appealing route for vaccine delivery.
In the study researchers vaccinated mice with microneedle patches containing influenza H5 VLPs derived from the H5N1 virus and found the resulting protective immunity to be equal to or higher than that induced from intramuscular inoculation. Significantly, human skin cells also responded to the influenza VLP vaccine delivered by the microneedle patch.
"Microneedle vaccination in the skin with H5 VLPs represents a promising approach for a self-administered vaccine against viruses with pandemic potential," say the researchers.
(J.M. Song, Y.C. Kim, A.S. Lipatov, M. Pearton, C.T. Davis, D.G. Yoo, K.M. Park, L.M. Chen, F.S. Quan, J.C. Birchall, R.O. Donis, M.R. Prausnitz, R.W. Compans, S.M. Kang. 2010. Microneedle delivery of H5N1 influenza virus-like particles to the skin induces long-lasting B- and T-cell responses in mice. Clinical and Vaccine Immunology, 17. 9: 1381-1389.)
New Class of Peptides May Protect Against Septic Shock
A new class of peptides may neutralize the endotoxin that causes sepsis, offering a new therapeutic strategy against an often lethal systemic bacterial infection. The researchers from Germany and Spain detail their findings in the September 2010 issue of the journal Antimicrobial Agents and Chemotherapy.
Septic shock, caused by systemic bacterial infections, kills more than 200,000 people each year in the U.S. alone despite intensive antibiotic treatment. Researchers are now looking to other resources such as natural proteins and peptides to neutralize the bacterial lipopolysaccharide (LPS) or endotoxin that causes sepsis, however, prior studies required such high peptide/LPS ratios that the peptide concentrations were deemed too toxic for human use.
Here, researchers designed a completely new class of peptides, synthetic anti-LPS peptides (SALPs), and preclinical studies in a mouse model showed high LPS neutralizing activity and significant protection against septic shock. Additionally, low toxicity levels potentially safe for humans were observed.
"Our results delineate a novel therapeutic strategy for the clinical management of patients with septic shock," say the researchers.
(T. Gutsmann, I. Razquin-Olazaran, I. Kowalski, Y. Kaconis, J. Howe, R. Bartels, M. Hornef, T. Schurholz, M. Rossle, S. Sanchez-Gomez, I. Moriyon, G. Martinez de Tejada, K. Brandenburg. 2010. New antiseptic peptides to protect against endotoxin-mediated shock. Antimicrobial Agents and Chemotherapy, 54. 9: 3817-3824.)
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