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Bacterially Produced Antifungal on Skin of Amphibians May Protect Against Lethal Fungus

A new study suggests that naturally occurring bacteria on the skin of salamanders could help protect other amphibians, including some species of endangered frogs, from a lethal skin disease. The researchers from James Madison University, Harrisonburg, Virginia and Vanderbilt University, Nashville, Tennessee report their findings in the November 2009 issue of the journal Applied and Environmental Microbiology.
Batrachochytrium dendrobatidis is a fungal pathogen that can cause a lethal skin disease in amphibians, however, some species remain relatively symptom free during infection. Innate immune factors, antimicrobial peptides, skin-associated microbial species, and behavior are all believed to attribute to the survival of some species over others. Researchers have found antifungal microbes to be of particular interest because their presence suggests they are mutualistic associates of amphibian species, meaning that there is a mutually beneficial relationship between the two organisms.
In a prior study Janthinobacterium lividum was identified as a bacterium that produces the anti-B. dendrobatidis metabolite violacein. Violacien was found on three of seven wild-collected red-backed salamanders (Plethodon cinereus) at concentration levels capable of inhibiting B. dendrobatidis, indicating a mutualistic community of violacein-producing bacteria. In this study researchers added J. lividum to the same species of red-backed salamanders and then exposed them to B. dendrobatidis. Results showed that adding J. lividum to the skin of the salamander increased the concentration levels of violacein already present and contributed to survival following experimental exposure to the fungus.
“Our study suggests that a threshold violacein concentration of about 18 μM on a salamander’s skin prevents mortality and morbidity caused by B. dendrobatidis,” say the researchers. “We show that over one-half of individuals in nature support antifungal bacteria that produce violacein, which suggests that there is a mutualism between violacein-producing bacteria and P. cinereus and that adding J. lividum is effective for protecting individuals that lack violacein-producing skin bacteria.
(M.H. Becker, R.M. Brucker, C.R. Schwantes, R.N. Harris, K.P. Minbiole. 2009. The bacterially produced metabolite violacein is associated with survival of amphibians infected with a lethal fungus. Applied and Environmental Microbiology, 75. 21: 6635-6638.)
New Therapy May be Effective Against Bacterial Infections and Sepsis
A new study found that certain immune cells primarily associated with asthma and allergies may enhance innate immunity and improve clearance of bacterial infections and may be an effective new therapy against bacterial infections and sepsis in humans. The researchers from Oregon Health and Science University, Portland and the Mayo Clinic, Scottsdale, Arizona report their findings in the November 2009 issue of the journal Infection and Immunity.
Sepsis, the systemic inflammatory response to infection, affects more than 700,000 people annually in the U.S. alone and is the leading cause of death in the intensive care unit. Ninety percent of reported cases are attributed to bacterial infections and mortality rates remain at 25% despite high quality supportive care and antibiotic treatment. Innate immune responses are vital to containing bacterial pathogens and recent studies link sepsis with impaired immunity. Antibiotic resistance and an increase in the mortality rate of sepsis patients due to the use of inappropriate antibiotics, as well as the role of the innate immune response in pathogen control highlight the need for new antimicrobial therapies.
''Eosinophils are white blood cells whose normal function is to protect the body against parasitic infections. They are also commonly associated with asthma and allergies. Numerous prior studies have noted the presence of Toll-like receptors (TLRs) on the surfaces of eosinophils indicating that they may play a part in recognizing and killing viruses and bacteria. In the study researchers found that isolated mouse eosinophils possessed antibacterial properties against Pseudomonas aeruginosa in vitro. In vivo, transgenic mice demonstrating high levels of eosinophils, showed improved clearance of P. aeruginosa, whereas bacterial clearance was impaired in mice with a congenital eosinophil deficiency suggesting an eosinophil specific effect.
“We provide evidence that mouse eosinophils and eosinphil granules play a beneficial but poorly defined role in innate immune responses to bacterial infections,” say the researchers. “Moreover, the data suggest that the administration of eosinophil-derived products may represent a viable adjuvant therapy for septic or bacteremic patients in the intensive care unit.”
(S.N. Linch, A.M. Kelly, E.T. Danielson, R. Pero, J.J. Lee, J.A. Gold. 2009. Mouse eosinophils possess potent antibacterial properties in vivo. Infection and Immunity, 77. 11: 4976-4982.)
Tooth-Binding Micelles Containing Antimicrobials May Provide Long-Term Cavity Protection
A new study suggests that tooth-binding micelles (or particles) may provide long-term cavity protection by adhering to tooth surfaces and gradually releasing encapsulated antimicrobials. Formulation of a mouthwash-based delivery system is anticipated, ultimately simplifying application and increasing at-home patient compliance. The researchers from the University of Nebraska Medical Center, Omaha and the University of Florida, Gainesville report their findings in the November 2009 issue of the journal Antimicrobial Agents and Chemotherapy.
One of the main contributing factors to dental cavities is overpopulation of acid-producing bacteria in the oral cavity that causes localized destruction of compromised dental hard tissue. Due to the episodic nature of cavities, long-term benefits of epochic treatments administered during routine office visits are minimal. Other delivery systems developed to maintain drug concentrations, including bioadhesive tablets, patches, films, and gels, aren’t very effective on the tooth surface and often cause irritation resulting in poor patient compliance. Emphasis on the need for therapeutic strategies that target the bacterial aspect of the disease and a delivery platform that would maintain the drug concentration on the tooth surface is warranted.
In the study tooth-binding micelles (molecular particles) were developed and encapsulated with farnesol, an antimicrobial recently found to be effective against the cavity causing bacterium Streptococcus mutans UA159. When tested on a model tooth surface the micelles were able to swiftly bind and gradually release the encapsulated farnesol. Additionally, biofilm inhibition studies of the farnesol-containing tooth-binding micelles demonstrated that they were able to inhibit S. mutans UA159 at much higher levels than untreated blank control micelles.
“A tooth-binding micelle delivery platform for the prevention and treatment of dental carries has been designed and prepared in this study,” say the researchers. “It is anticipated that the tooth-binding micelles have the potential to be formulated into mouth rinses that may have the merits of simple application, cultural acceptance, and improved patient compliance.”
(F. Chen, X.M. Liu, K.C. Rice, X. Li, F. Yu, R.A. Reinhardt, K.W. Bayles, D. Wang. 2009. Tooth-binding micelles for dental carries prevention. Antimicrobial Agents and Chemotherapy, 53. 11: 4898-4902.)

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