Resistance to First-Line Anti-TB Drugs Is Associated with Reduced Nitric Oxide Susceptibility in Mycobacterium tuberculosis 英文参考文献.docVIP

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Resistance to First-Line Anti-TB Drugs Is Associated with Reduced Nitric Oxide Susceptibility in Mycobacterium tuberculosis 英文参考文献.doc

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Resistance to First-Line Anti-TB Drugs Is Associated with Reduced Nitric Oxide Susceptibility in Mycobacterium tuberculosis 英文参考文献

ResistancetoFirst-LineAnti-TBDrugsIsAssociatedwith ReducedNitricOxideSusceptibilityinMycobacterium tuberculosis JonnaIdh1*,MekidimMekonnen2,3,EbbaAbate1,3,4,WassihunWedajo3,JimWerngren5, KristianAngeby¨ 6,MariaLerm1,DanielElias7,TommySundqvist1,AbrahamAseffa3,OlleStendahl1, ThomasScho¨n8 1DivisionofMicrobiologyandMolecularMedicine,FacultyofHealthSciences,Linko¨pingUniversity,Linko¨ping,Sweden,2DepartmentofMicrobiology,Immunologyand Parasitology,AddisAbabaUniversity,DebreZeit,Ethiopia,3ArmauerHansenResearchInstitute,AddisAbaba,Ethiopia,4DepartmentofMicrobiologyandParasitology, Gondar University Hospital, Gondar, Ethiopia, 5Unit ofHighlyPathogenicMicroorganisms, Department ofPreparedness, Swedish Institute for CommunicableDisease Control,Solna,Sweden,6ClinicalMicrobiology,MTC,KarolinskaInstitute,KarolinskaUniversityHospital,Stockholm,Sweden,7DepartmentofCancerandInflammation, InstituteofMolecularMedicine,UniversityofSouthernDenmark,Odense,Denmark,8DepartmentofInfectiousDiseasesandDepartmentofClinicalMicrobiology,Kalmar CountyHospital,Kalmar,Sweden Abstract Background and Objective: The relative contribution of nitric oxide (NO) to the killing of Mycobacterium tuberculosis in humantuberculosis(TB)iscontroversial,althoughthishasbeenfirmlyestablishedinrodents.Studieshavedemonstrated thatclinicalstrainsofM.tuberculosisdifferinsusceptibilitytoNO,buthowthiscorrelatestodrugsusceptibilityandclinical outcomeisnotknown. Methods: In this study, 50 sputum smear- and culture-positive patients with pulmonary TB in Gondar, Ethiopia were included.Clinicalparameterswererecordedanddrugsusceptibilityprofileandspoligotypingpatternswereinvestigated. NOsusceptibilitywasstudiedbyexposingthestrainstotheNOdonorDETA/NO. Results:ClinicalisolatesofM.tuberculosisshowedadose-andtime-dependentresponsewhenexposedtoNO.Themost frequentspoligotypesfoundwereCAS1-DelhiandT3_ETHinatotalofnineknownspoligotypesandfourorphanpatterns. TherewasasignificantassociationbetweenreducedsusceptibilitytoNO(.