Despite their ecologic similarity, soils from three geographically distinct areas of the American southwest harbor vastly different collections of small, biosynthetic genes, a finding that suggests the existence of a far greater diversity of potentially useful products than was previously supposed. The research is published in the May issue of Applied and Environmental Microbiology.

Natural compounds have been the sources of the majority of new drugs approved by the US Food and Drug Administration, and bacteria have been the biggest single source of these therapeutically relevant compounds. Most bacterially-derived antibiotic and anticancer agents were discovered by culturing bacteria from environmental samples, and then examining the metabolites they produce in laboratory fermentation studies. But the vast majority of bacterial species cannot be cultured, which suggested that the world might be awash in potentially useful, but unknown bacterial metabolites.

In this study, Sean Brady of the Howard Hughes Medical Institute, Rockefeller University, New York, NY, and colleagues extracted DNA from soils from the Sonoran Desert of Arizona, the Anza Borrego section of the Sonoran Desert of California, and the Great Basin Desert of Utah. They used this DNA to construct very large metagenomic DNA libraries, and screened these libraries for three of the most common classes of small molecule biosynthesis systems, type I modular polyketides, type II iterative polyketides, and non-ribosomal peptides, says Brady.

The investigators used PCR to amplify collections of gene fragments from each of the three libraries and compared these to assess the similarities and differences between the collections of genes cloned from each environment, says Brady.

"Our work suggests that the genomes of environmental bacteria could encode many additional drug-like molecules, including compounds that might serve, among other things, as new antibiotics and anticancer agents," says Brady. "This is a small preliminary study that warrants additional investigations of more environments and more extensive sequence analysis, but it suggests that environmental bacteria have the potential to encode a large additional treasure trove of new medicines."

More information: B.V.B. Reddy, D. Kallifidas, J.H. Kim, Z. Charlop-powers, Z. Feng, and S.F. Brady, 2012. Natural product biosynthetic gene diversity in geographically distinct soil microbiomes. Appl. Environ. Microbiol. 78:3744-3752.

Journal reference: Applied and Environmental Microbiology

Provided by American Society for Microbiology

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Genes culled from desert soils suggest potential medical resource

Public release date: 22-May-2012 [ | E-mail | Share ]

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Researchers have uncovered what makes one particular strain of methicillin-resistant Staphylococcus aureus (MRSA) so proficient at picking up resistance genes, such as the one that makes it resistant to vancomycin, the last line of defense for hospital-acquired infections. They report their findings in mBio, the online open-access journal of the American Society for Microbiology, on Tuesday May 22.

"MRSA strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistant S. aureus (VRSA) infection in the United Statesall CC5 strains," write the researchers from Harvard, the Massachusetts Eye and Ear Infirmary in Boston and the Broad Institute in Cambridge and other institutions. "Vancomycin is a key last-line bactericidal drug for treating these infections."

The CC5 strain of MRSA has managed to acquire resistance to vancomycin on 12 separate occasions, and although it hasn't spread widely yet, the risk that MRSA could eventually overwhelm even our last-line drugs is a very serious one. In the study, the researchers sequenced the genomes of all available vancomycin-resistant MRSA strains to find what distinguishes them from other lineages and why CC5 is apparently more adept than other strains at picking up vancomycin resistance.

They report that vancomycin-resistant MRSA strains and other CC5 lineages have some important differences from other types of MRSA, including adaptations that allow them to co-exist with other types of bacteria and may help them take up foreign DNA. They all lack the operon called bsa, for instance, a set of genes that encode a lantibiotic bacteriocin, an antibiotic protein made by bacteria to kill other bacteria. This is important, say the authors, because it enables CC5 to get along well with other bacteria in mixed infections. Instead of killing off competing organisms, CC5 aims to co-exist. This enables it to pick up genes - like the one that encodes vancomycin resistance - from unexpected places. Mixed infections are breeding grounds for antibiotic resistance because they encourage the exchange of genes among very different kinds of organisms.

In roughly the place where these bacteriocin genes are missing is a unique cluster of genes that encode enterotoxins, proteins that attack the human host and, again, could make it easier for mixed populations of bacteria to grow at infection sites.

Finally, CC5 has a mutation in a gene called dprA, which is known to influence the ability to assimilate foreign DNA. The mutation could alter or eliminate the function of dprA in CC5 strains of MRSA, making it amenable to taking up DNA from outside sources.

The sum of all these traits, including the lack of bacteriocin production, the ability to produce enterotoxins, and mutations in the ability to assimilate foreign DNA, is a lineage of S. aureus that is optimized to grow in exactly the types of multi-species infections where gene transfer could occur.

This makes CC5 a dangerous organism in hospitals, say the authors. In hospitals, pathogens are under continuous pressure from antibiotics to survive and evolve, and CC5 isolates appear to be very well adapted to succeed by acquiring new resistances. Frequent use of antibiotics in hospital patients could select for strains like CC5 that have an enhanced ability to co-exist with bacteria that provide genes for antibiotic resistance.

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How one strain of MRSA becomes resistant to last-line antibiotic

Public release date: 21-May-2012 [ | E-mail | Share ]

Contact: Garth Hogan ghogan@asmusa.org American Society for Microbiology

Ellen Jo Baron, Ph.D., D(ABMM), Professor Emerita, Stanford University School of Medicine, Stanford, California, has been honored with the 2012 ASM Founders Distinguished Service Award for her years of volunteer service to ASM. "For as long as I can recall during my career in clinical microbiology, Baron has been the heart and soul of my profession," says Wm. Michael Dunne, Ph.D., Executive Director of Research and Development, North America, for bioMrieux, Inc., Durham, NC.

Baron holds a Ph.D. in Medical Microbiology from the University of Wisconsin, Madison, and completed a post-doctoral fellowship in Clinical Microbiology and Laboratory Medicine at UCLA and the Wadsworth Veterans Affairs Medical Center. At Stanford, Baron served as Director of the Clinical Microbiology and Clinical Virology Laboratories and Associate Chair of Pathology for Faculty Development and Diversity in the School of Medicine. Baron is currently Director of Medical Affairs for Cepheid, a high-technology molecular diagnostics company in Sunnyvale, California, where she writes the On-Demand Newsletter and works on clinical trials, new test development, and publications involving Cepheid products. She serves as an internal and external educator about the technology and its impact on patient care.

Baron's numerous contributions to ASM encompass a vast variety of programs. "Baron is one of those unsung treasures of ASM; she has worked diligently for the society, both locally and nationally, for over 35 years," describes nominator Fred Tenover of Cepheid. Baron has served as Chair of ASM's largest scientific division, Division C (Clinical Microbiology), and is now the Divisional Representative for Group 1. In addition, she is a Diplomate of the American Board of Medical Microbiology and a Fellow of the American Academy of Microbiology. She has also been involved at the branch level, has served as a volume editor for four editions of the Manual of Clinical Microbiology, and has promoted the field of clinical microbiology to undergraduate and graduate students throughout the United States and the world. "I am in awe of her energy and her tireless efforts to not only promote ASM, but to promote the field of Medical Microbiology and to ensure a minimum standard of excellence in clinical laboratory practice throughout the world," says Karen Carroll, Johns Hopkins University School of Medicine.

In addition to her extensive service to the ASM, Baron has also volunteered her time to many other entities. She is a past microbiology representative on the Center for Medicaid and Medicare Services Clinical Laboratory Improvement Advisory Committee, and served for almost 10 years on the Council of Clinical Advisors for the NIH Clinical Laboratories. Baron has been on the editorial boards of several key clinical microbiology journals, has written or edited over 30 books and chapters, and is widely published in peer-reviewed journals in the area of diagnostic microbiology and infectious diseases (with over 100 publications). She is a past recipient of ASM's bioMrieux Sonnenwirth Award for Leadership in Clinical Microbiology and the Alice C. Evans Award for serving as a role model for women in the field. She won the Kenneth L. Vosti Teaching Award from the Infectious Diseases Division at Stanford, and is a Fellow of the Infectious Diseases Society of America. Baron currently serves as a representative on the Clinical Laboratory Standards Institute's Microbiology Area Resource Committee.

Baron is also very active in the field of diagnostic microbiology as a symposium presenter and author. For the World Health Organization, she co-developed the program for antimicrobial resistance monitoring and basic microbiology, which she presented in a number of resource-poor countries from 1995-1998 and again in 2005. In 2007, Baron developed a new basic microbiology training program for developing world sites, which has been presented in Colombia, Laos, Cambodia, Botswana, Zambia, Mozambique, China, Panama, and El Salvador, as well as in the U.S. This program is supported by grants from the Mrieux Foundation, Pan-American Health Organization, and ASM's LabCap Committee. The program will eventually be used throughout the entire developing world. Baron is Secretary-Treasurer of Diagnostic Microbiology Development Program, a non-profit organization that she co-founded to support microbiology laboratory development in the resource-limited areas of the world.

"In short, I can think of no one more deserving of an award for outstanding volunteer service, and for dedication to the pursuit of the goals of the ASM, than Baron," summarized Carroll. "She truly embodies the spirit of our discipline."

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To view Dr. Baron's biosketch, please visit: http://www.asm.org/index.php/awards-grants/current-asm-founders-distinguished-service-award-laureate.html

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The American Society for Microbiology honors Ellen Jo Baron