Butler County Solid Waste Commission, June 30, 2001 & June 30, 2002

Other Audit Reports

Jones County Solid Waste Management Commission, June 30, 2002 & June 30, 2003

Other Audit Reports

Hardin County Sanitary Solid Waste Disposal Commission, June 30, 2003

Other Audit Reports

Shelby County Area Solid Waste Agency, June 30, 2002 & June 30, 2003

Other Audit Reports

Butler County Solid Waste Commission, June 30, 2002 & June 30, 2003

Other Audit Reports

Pocahontas County Solid Waste Commission, June 30, 2003

Other audit reports - Solid Waste Commission

Wayne-Ringgold-Decatur County Solid Waste Management Commission, June 30, 2002 & June 30, 2003

Other Audit Reports

Prairie Solid Waste Agency, June 30, 2003 and 2002

Audit report on the Prairie Solid Waste Agency, fiscal years ending June 30, 2003 and 2002.

Crawford County Area Solid Waste Agency Commission, June 30, 2003 and 2002

Audit report on the Crawford County Area Solid Waste Agency Commission, fiscal year ending June 30, 2003 and 2002.

Delaware County Solid Waste Disposal Commission, June 30, 2003 & 2002

Other Audit Report

Understanding the two-component sensing System of virulent bacteria

Report for the scientific sojourn carried out at the l’ Institute for Computational Molecular Science of the Temple University, United States, from 2010 to 2012. Two-component systems (TCS) are used by pathogenic bacteria to sense the environment within a host and activate mechanisms related to virulence and antimicrobial resistance. A prototypical example is the PhoQ/PhoP system, which is the major regulator of virulence in Salmonella. Hence, PhoQ is an attractive target for the design of new antibiotics against foodborne diseases. Inhibition of the PhoQ-mediated bacterial virulence does not result in growth inhibition, presenting less selective pressure for the generation of antibiotic resistance. Moreover, PhoQ is a histidine kinase (HK) and it is absent in animals. Nevertheless, the design of satisfactory HK inhibitors has been proven to be a challenge. To compete with the intracellular ATP concentrations, the affinity of a HK inhibidor must be in the micromolar-nanomolar range, whereas the current lead compounds have at best millimolar affinities. Moreover, the drug selectivity depends on the conformation of a highly variable loop, referred to as the “ATP-lid, which is difficult to study by X-Ray crystallography due to its flexibility. I have investigated the binding of different HK inhibitors to PhoQ. In particular, all-atom molecular dynamics simulations have been combined with enhanced sampling techniques in order to provide structural and dynamic information of the conformation of the ATP-lid. Transient interactions between these drugs and the ATP-lid have been identified and the free energy of the different binding modes has been estimated. The results obtained pinpoint the importance of protein flexibility in the HK-inhibitor binding, and constitute a first step in developing more potent and selective drugs. The computational resources of the hosting institution as well as the experience of the members of the group in drug binding and free energy methods have been crucial to carry out this work.

Waste Matters, July 2003

Newsletter for Department of Natural Resources, Waste Management Division

Waste Matters, May 2004

Newsletter produced by Department Natural Resources, Waste Managment Division

Waste Matters, September 2004

Newsletter prdouced by Department of Natural Resources, Waste Matters Division