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WELCOME TO THE 2011 - Harvard Initiative for Global Health ...

WELCOME TO THE 2011 - Harvard Initiative for Global Health ...

Background: Pakistan has

Background: Pakistan has a high prevalence of both TB (330 per 100,000) and hepatitis C virus (HCV) (4-5% of the general population). In areas of low-HIV prevalence, other co-morbid diseases are of increasing importance for the control and management of TB. Treatment outcomes in cohorts of co-infected (TB-HCV) cases have not been previously reported from Pakistan. Methods: A retrospective, medical record abstraction was conducted on all adult drugsusceptible TB cases screened for HCV between Jan 2008 and Mar 2012 at the Indus Hospital TB Control Program. Results: 1,684 TB cases were screened for HCV infection and 221 (13%) were found to be coinfected. TB-HCV prevalence was significantly higher in males compared with females (17% vs 10%, p

the permeability of drugs to the pathogen, and ultimately improve the treatment of tuberculosis and other mycobacterial diseases. Grant acknowledgments: This study is supported by NIH funding NIAID AI 45617, American Lung Association RG-107-N; and The Pilot Grant from CTSI and BU Evan’s Foundation. 27) Inhibition of the fatty acid enoyl-acyl carrier protein reductase (FabI) from Staphylococcus aureus Michael V. Baxter, 1, Andrew Chang, 1,2, Hao Lu, 1 Johannes Schiebel, 3 Caroline Kisker, 3,* Peter J. Tonge 1,* 1 Institute for Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, USA; 2 Medical Scientist Training Program, Stony Brook University, Stony Brook, New York 11794-3400, USA ; 3 Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, Josef- Schneider-Str. 2, D-97080 Würzburg, Germany Staphylococcus aureus is a worldwide health problem and it is estimated that over 33% of the worlds population is a carrier. Drug resistant strains of this gram-positive bacterium, such as methicillin-resistant S. aureus (MRSA) have become a serious health threat. Currently, vancomycin is used as the last line of defense for MRSA patients. However, with the recent emergence of a vancomycin-resistant S. aureus (VRSA) strain, the demand for novel antibiotics, with unique modes of action, is of extreme importance. The enoyl-ACP reductase (FabI) is a rate-limiting enzyme in the type II fatty acid biosynthesis (FAS-II) pathway. However, recent studies have debated the essentiality of the FAS-II pathway, since bacteria can integrate exogenous fats into cell membranes. Branched-chain substrate mimics were synthesized to test for specificity of incorporation, by S. aureus. Kinetic analysis shows that S. aureus prefers the incorporation of branched-chain fatty acids (BCFA). BCFA are a significant portion of the S. aureus cell membrane, therefore critical for the in vivo survival of S. aureus. Human serum only contains trace amounts of BCFA, therefore this suggests potential rationale for S. aureus FAS-II essentiality. Novel drugs, targeting saFabI, are designed to maximize residence time through slow onset inhibition. A chlorinated and fluorinated derivative of the slow onset inhibitor PT119 was synthesized to optimize the residence time. Kinetic analysis revealed that the chloro group on the A-ring as well as the cyano group on the B-ring increases the residence time of the drug on its target. Future drugs will continue to be synthesized based off of crystal structures and computational docking. This work was supported with funding from Astra Zeneca Collaboration 1101544 and TRO Fusion Award 1076817. 28) In vitro susceptibility of Mycobacterium smegmatis to extracts from Cameroonian medicinal plants Valerie Flore, Brian Schuster, Fabrice Fekam Boyom, Eric Rubin, Donkeng Donfack Life and Health Sciences Research Institute Aim Tuberculosis (TB) is a bacterial disease caused by Mycobacterium tuberculosis. One third of the world’s population is infected each year. This high incidence of infection called for an urgent need to develop new anti-tuberculosis drugs. Within this framework, plants products have proven interesting antimicrobial potency. This study was conducted to determine the in vitro activity of extracts from four Cameroonian medicinal plants against Mycobacterium smegmatis, a closely related to the causative agent of TB. 30

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