Tips from the journals of the American Society for Microbiology

Compound Found in Plant Products May Offer New Treatment for Malaria

In a new study researchers from France suggest that ellagic acid, a compound found in plant products, may be effective against malaria and ultimately lead to new forms of treatment. They report their findings in the March 2009 issue of the journal Antimicrobial Agents and Chemotherapy.

Malaria is considered to be one the most significant causes of infectious disease worldwide. Increasing resistance to current drugs has emphasized the need for new forms of treatment. Recently initiated collaborative programs with West African countries have allowed researchers to explore methods used by traditional healers and local populations against malaria. Plants were found to be commonly used and laboratory testing for antimalarial activity of extracts resulted in the identification of ellagic acid.

In the study researchers performed further in vivo and in vitro testing to clarify the levels of antimalarial properties of ellagic acid. Results showed high activity in vitro against all strains of Plasmodium falciparum, one species of the parasite that causes malaria in humans, regardless of their resistance to other antimalarial drugs. Ellagic acid was also found to be active in vivo against Plamodium vinckei petteri in curative, suppressive, and prophylactic murine tests without any toxicity. Final findings by the researchers suggest that ellagic acid may enhance the activity of current antimalarial drugs such as chloroquine, mefloquine, artesunate, and atovaquone.

“Ellagic acid has in vivo activity against plasmodia, but modification of the compound could lead to improved pharmacological properties, principally for the oral route,” say the researchers.

(P. Njomnang Soh, B. Witkowski, D. Olagnier, M. Nicolau, M. Garcia-Alvarez, A. Berry, F. Benoit-Vical. 2009. In vitro and in vivo properties of ellagic acid in malaria treatment. Antimicrobial Agents and Chemotherapy, 53. 3: 1100-1106.)

New Vaccine May Protect Against Campylobacter jejuni

A new conjugate vaccine containing the capsule polysaccharides from two strains of Campylobacter jejuni, a major cause of bacterial diarrhea worldwide, provided protection against infection in mice and monkeys and may ultimately have human implications. The researchers from the University of Guelph, Ontario, Canada, the Naval Medical Research Center, Silver Spring, Maryland and the Naval Medical Research Center Detachment, Lima, Peru report their findings in the March 2009 issue of the journal Infection and Immunity.

C. jejuni infection is the leading cause of diarrheal disease in the U.S. as well as some developing countries and is also associated with reactive arthritis, irritable bowel syndrome, and Guillain Barre syndrome (GBS) which occurs when the body’s immune system attacks part of the peripheral nervous system. Due to several hurdles in the research process, mainly the association of C. jejuni with GBS and that C. jejuni has proven to be unresponsive to studies on molecular pathogenesis, no licensed vaccines are currently available.

The capsule polysaccharide (CPS) of C. jejuni is one of the few virulence factors that have been identified. Due to the success of CPS conjugate vaccines against other mucosal pathogens the researchers in this study used CPSs from two strains of C. jejuni (81-176 and CG8486) to develop a vaccine and tested its effectiveness in mice and monkeys challenged with C. jejuni infection. Following subcutaneous vaccination mice demonstrated significant immune response and reduction in disease. The CPS 81-176 vaccine elicited 100% protection against diarrhea in the New World monkey, Aotus nancymaae.

“The C. jejuni CPS conjugate vaccines synthesized in this study were immunogenic in mice and reduced the diseases following intranasal challenge with the homologous strain of C. jejuni,” say the researchers. “We also show here that the 81-176 CPS conjugate vaccine is immunogenic and 100% protective against diarrheal disease in New World monkeys.”

(M.A. Monteiro, S. Baqar, E.R. Hall, Y. Chen, C.K. Porter, D.E. Bentzel, L. Applebee, P. Guerry. 2009. Capsule polysaccharide conjugate vaccine against diarrheal disease caused by Campylobacter jejuni. Infection and Immunity, 77. 3: 1128-1136.)

New Combination Therapy May Protect Against Implant-Associated MRSA Infections

A new study suggests that combination therapy using the antibiotics linezolid and rifampin may effectively treat drug-resistant MRSA implant-associated infections. The researchers from Switzerland report their findings in the March 2009 issue of the journal Antimicrobial Agents and Chemotherapy.

Implanted devices are increasingly used in today’s medical community to alleviate pain and improve mobility and function. As a result, the number of implant-associated infections (when bacteria adhere to the implant surface and become imbedded in a protective layer, also known as a biofilm) are also on the rise. The protective layering of biofilms often results in high rates of antimicrobial resistance and failed treatment. Removal of the implant becomes necessary, therefore increasing health care costs and risk of death.

Staphylococcus aureus is the known cause of the majority of implant-associated infections and treatment with antibiotics capable of acting on surface-adhering bacteria is critical. Rifampin is an antibiotic used to treat surface-adhering staphylococci, however when used independently resistance rapidly occurs. Rifampin in conjunction with quinolones can successfully treat implant-related infections but quinolone resistance is also on the rise emphasizing the need for alternative therapies. Linezolid is an antibiotic proven active against staphylococci, including MRSA.

In the study researchers tested the ability of linezolid, alone or in combination with rifampin, against MRSA implant-associated infections in vitro and a guinea pig model. Time-kill studies showed bacterial regrowth and the development of resistance after 24 hours with rifampin alone, however both were prevented by the addition of linezolid. Guinea pigs with implant infections were then treated with antimicrobial combinations twice daily for 4 days. Linezolid alone reduced bacteria and prevented regrowth for 5 days after treatment ended. Linezolid in combination with rifampin achieved higher reduction in bacterial levels as well as cure rates of 50 to 60%.

“The linezolid-rifampin combination is a treatment option for implant-associated infections caused by quinolone-resistant MRSA,” say the researchers.

(D. Baldoni, M. Haschke, Z. Rajacic, W. Zimmerli, A. Trampuz. 2009. Linezolid alone or combined with rifampin against methicillin-resistant Staphylococcus aureus in experimental foreign-body infection. Antimicrobial Agents and Chemotherapy, 53. 3: 1142-1148.)

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