Archive for February 8, 2013

Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus

Proceedings of the National Academy of Sciences

Jonathan S. Edwardsa,1, Laurie Bettsb, Monica L. Fraziera,2, Rebecca M. Polleta, Stephen M. Kwongc,William G. Walton

b, W. Keith Ballentine IIIb, Julianne J. Huangb, Sohrab Habibib, Mark Del Campod,Jordan L. Meiere, Peter. B. Dervane, Neville Firthc, and Matthew R. Redinboa,b,3Departments of aBiochemistry and Biophysics and b Chemistry, University of North Carolina, Chapel Hill, NC 27599; c School of Biological Sciences, University of Sydney, Sydney, NSW 2006, Australia; d Rigaku Americas Corporation, The Woodlands, TX 77381; and e Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91106

Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase–DNA complex crystal structure reveals unique protein–DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase. This conclusion is supported by a smallangle X-ray scattering structure of a full-length, 665-residue NES–DNA complex. Together, these data reveal the structural basis for antibiotic multiresistance acquisition by S. aureus and suggest novel strategies for therapeutic intervention.



February 8, 2013 at 10:06 am

Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008

Emerging Infectious Diseases March 2013 V.19 N.3

John A. Painter , Robert M. Hoekstra, Tracy Ayers, Robert V. Tauxe, Christopher R. Braden, Frederick J. Angulo, and Patricia M. Griffin

Centers for Disease Control and Prevention, Atlanta, GA, USA

Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.


February 8, 2013 at 10:03 am


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