A grant from the National Institutes of Health (NIH) is helping sceintists examine the genetics of multidrug tolerance in bacteria. This four-year grant will enable Dr. Kim Lewis, a professor of biology at Northeastern University, continue to research the formation of dormant persister bacterial cells, which are tolerant to all known antibiotics and make many infections basically incurable. 

By using the genomics approach, the team hopes to identify the genes responsible for the formation and maintenance of these cells and to develop a therapy to treat them.

“The goal of this research project is to identify the mechanism behind the phenomenon of resistant bacteria,” said Lewis. “We know that pathogens produce dormant persister cells, which then resist antibiotics, but we need to know how it happens in order to develop effective treatments against these dormant cells.”

The first part of this research project is to produce mutants with the capacity to produce a large number of dormant persister cells. The researchers will work with two bacteria, E. coli and Y. pestis, to produce high persistence (hip) mutants with the ability to produce large amounts of persister cells.

The next phase will be done in collaboration with James Galagan, PhD, an associate director at the Broad Institute of MIT and Harvard and a co-investigator for this grant, where they will sequence the genomes of 100 hip mutants to identify the mutations, which will help decipher the mechanism responsible for antibiotic tolerance.

According to the NIH, the study has the potential to provide viable clinical strategies to manage infections in which persister cells are the main driver of suboptimal response to antibiotic treatment and consequently revolutionize antibiotic targeting and therapy.

Founded in 2006, Northeastern University’s Anti-Microbial Discovery Center is to translate basic science discoveries into novel antimicrobial therapies to combat biowarfare and conventional pathogen threats.

Researchers say drug discovery is in a state of crisis. The last class of broad-spectrum compounds, the fluoroquinolones, was discovered 40 years ago. The rise of multidrug resistant pathogens and the threat of genetically engineered bioweapons represent an urgent need for novel antimicrobial therapies. Funded by grants from the NIH, National Science Foundation, and Department of Energy, the center is directed by Dr. Lewis and draws faculty members from biology, chemistry, physics, and pharmaceutical sciences.

– by the Editors

Genes of bacteria key to new treatments, NIH researchers say.

Posted: April 18th, 2008 under Developing Diseases, Genetics & Gene Therapies, Impaired Immunity.
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The National Institutes of Health (NIH) has awarded a two-year, $2.0 million grant to a San Diego-based firm, Vical Incorporated (Nasdaq: VICL) to fund the ongoing development of Vical’s immunotherapeutic plasmid DNA (pDNA) vaccine for herpes simplex virus type 2 (HSV-2), a sexually transmitted virus and the leading cause of genital herpes.

Researchers said the  HSV-2 vaccine will also be evaluated with Vical’s innovative Vaxfectin (R: 63.71, -2.97, -4.45%) adjuvant.

The pre-clinical development activities covered by the grant will be conducted at the University of Washington School of Medicine and the University of Texas Medical Branch, both centers of excellence in herpes research. The vaccine will be designed for use in people already infected with HSV-2, with the goal of reducing or eliminating periodic viral flare-ups.

According to Vijay B. Samant, Vical’s president and chief executive officer, chronic antiviral treatment carries a significant healthcare cost and contributes to the emergence of drug-resistant strains and increasing infection rates. “A therapeutic vaccine that could control disease symptoms and transmission would be a welcome addition to the HSV-2 treatment arsenal. We are pleased to collaborate with leading academic research centers in addressing this critical public health need,” says Samant.

According to David Koelle, professor of medicine in the Division of Allergy and Infectious Diseases at the University of Washington School of Medicine, technologies such as pDNA vaccines can contribute to priming and boosting CD8 T-cell responses to HSV-2, have the best chance of changing the natural history of established HSV-2 infection, potentially improving symptoms, lesions, shedding, and perhaps even transmission.

The grant supplements the $300,000 awarded to Vical in 2005 for the HSV-2 vaccine program.

– The Editors

Lesions are a common symptom of HSV-2. Image Source: University of Iowa.

Posted: April 17th, 2008 under Diseases, Genetics & Gene Therapies, Herpes, Herpes-Cold Sores, Sexually Transmitted Diseases.
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