Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment

Hdl Handle:
http://hdl.handle.net/10144/114155
Title:
Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment
Authors:
Feuerriegel, Silke; Cox, Helen S; Zarkua, Nana; Karimovich, Hamraev A; Braker, Kai; Rüsch-Gerdes, Sabine; Niemann, Stefan
Journal:
Antimicrobial Agents and Chemotherapy
Abstract:
The rapid detection of Mycobacterium tuberculosis isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n = 26) and to capreomycin and/or amikacin (n = 48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs, and tlyA). Strains susceptible to ofloxacin (n = 49) and capreomycin and/or amikacin (n = 39) were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in gyrA at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in gyrB, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40 strains [85.0%]). Three strains had mutations in tlyA, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.
Affiliation:
Research Center Borstel, National Reference Center for Mycobacteria, Parkallee 18, 23845 Borstel, Germany; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia; Medecins Sans Frontieres, Tashkent, Uzbekistan; Ministry of Health, Nukus, Karakalpakstan, Uzbekistan; Medecins Sans Frontieres, Berlin, Germany
Issue Date:
26-May-2009
URI:
http://hdl.handle.net/10144/114155
DOI:
10.1128/AAC.00050-09
PubMed ID:
19470506
Additional Links:
http://aac.asm.org/cgi/content/full/53/8/3353?view=long&pmid=19470506
Type:
Article
Language:
en
ISSN:
1098-6596
Appears in Collections:
TB

Full metadata record

DC FieldValue Language
dc.contributor.authorFeuerriegel, Silkeen
dc.contributor.authorCox, Helen Sen
dc.contributor.authorZarkua, Nanaen
dc.contributor.authorKarimovich, Hamraev Aen
dc.contributor.authorBraker, Kaien
dc.contributor.authorRüsch-Gerdes, Sabineen
dc.contributor.authorNiemann, Stefanen
dc.date.accessioned2010-10-29T15:50:58Z-
dc.date.available2010-10-29T15:50:58Z-
dc.date.issued2009-05-26-
dc.identifier.citationAntimicrob. Agents Chemother 2009;53(8):3353-6en
dc.identifier.issn1098-6596-
dc.identifier.pmid19470506-
dc.identifier.doi10.1128/AAC.00050-09-
dc.identifier.urihttp://hdl.handle.net/10144/114155-
dc.description.abstractThe rapid detection of Mycobacterium tuberculosis isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n = 26) and to capreomycin and/or amikacin (n = 48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs, and tlyA). Strains susceptible to ofloxacin (n = 49) and capreomycin and/or amikacin (n = 39) were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in gyrA at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in gyrB, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40 strains [85.0%]). Three strains had mutations in tlyA, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.en
dc.language.isoenen
dc.relation.urlhttp://aac.asm.org/cgi/content/full/53/8/3353?view=long&pmid=19470506en
dc.rightsPublished by American Society for Microbiology Archived on this site with permission and copyright by the American Society for Microbiologyen
dc.subject.meshAmikacinen
dc.subject.meshAntitubercular Agentsen
dc.subject.meshBacterial Proteinsen
dc.subject.meshCapreomycinen
dc.subject.meshDNA Gyraseen
dc.subject.meshExtensively Drug-Resistant Tuberculosisen
dc.subject.meshHumansen
dc.subject.meshMutationen
dc.subject.meshMycobacterium tuberculosisen
dc.subject.meshOfloxacinen
dc.subject.meshSequence Analysis, DNAen
dc.subject.meshTuberculosis, Multidrug-Resistanten
dc.subject.meshUzbekistanen
dc.titleSequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatmenten
dc.typeArticleen
dc.contributor.departmentResearch Center Borstel, National Reference Center for Mycobacteria, Parkallee 18, 23845 Borstel, Germany; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia; Medecins Sans Frontieres, Tashkent, Uzbekistan; Ministry of Health, Nukus, Karakalpakstan, Uzbekistan; Medecins Sans Frontieres, Berlin, Germanyen
dc.identifier.journalAntimicrobial Agents and Chemotherapyen
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