First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in Kuwait
<p>Abstract</p> <p>Background</p> <p>Nearly 5% of all <it>Mycobacterium tuberculosis </it>strains worldwide are resistant at least to rifampicin and isoniazid (multidrug-resistant tuberculosis, MDR-TB). Inclusion of a fluoroquinolone and an injectable agent...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-04-01
|
| Series: | BMC Research Notes |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1756-0500/4/123 |
| _version_ | 1818521168809820160 |
|---|---|
| author | Ahmad Suhail Al-Mutairi Noura M Mokaddas Eiman |
| author_facet | Ahmad Suhail Al-Mutairi Noura M Mokaddas Eiman |
| author_sort | Ahmad Suhail |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Nearly 5% of all <it>Mycobacterium tuberculosis </it>strains worldwide are resistant at least to rifampicin and isoniazid (multidrug-resistant tuberculosis, MDR-TB). Inclusion of a fluoroquinolone and an injectable agent (kanamycin, amikacin or capreomycin) in multidrug therapy is crucial for proper treatment of MDR-TB. The incidence of MDR-TB in Kuwait is ~1%. MDR-TB strains additionally resistant to fluoroquinolones and injectable agents are defined as extensively drug-resistant (XDR-TB) strains and have been detected in >55 countries. Infections with XDR-TB strains have very poor prognosis. This study detected the occurrence of <it>gyrA </it>mutations associated with fluoroquinolone resistance among MDR-TB strains in Kuwait.</p> <p>Findings</p> <p>Direct DNA sequencing of quinolone resistance-determining region of <it>gyrA </it>gene was performed to detect fluoroquinolone resistance-associated mutations in 85 MDR-TB strains isolated from 55 TB patients and 25 pansusceptible <it>M. tuberculosis </it>strains. For isolates exhibiting <it>gyrA </it>mutations, 3'-end of <it>rrs </it>(16S rRNA) was sequenced for the detection of XDR-TB. Fingerprinting of fluoroquinolone resistant MDR-TB strains was performed by detecting mutations in three (81 bp hot-spot, N-terminal and cluster II) regions of <it>rpoB</it>, <it>katG </it>codon 315 and <it>inhA</it>-regulatory region, polymorphisms at <it>gyrA </it>codon 95 and <it>katG </it>codon 463 by DNA sequencing and by double-repetitive-element PCR for determining strain relatedness. None of the pansusceptible but six of 85 MDR-TB strains contained <it>gyrA </it>mutations. Only <it>gyrA </it>codon 94 was mutated in all six (D94A in one and D94G in five) strains. Three of six mutant strains were recovered from the same patient while three other strains represented individual patient isolates. Fingerprinting studies identified all individual patient isolates as epidemiologically distinct strains. All six strains with a <it>gyrA </it>mutation contained wild-type <it>rrs </it>sequence.</p> <p>Conclusions</p> <p>Although fluoroquinolones are generally not used for chemotherapy of TB and drug susceptibility testing for second-line drugs is not carried out in Kuwait, four of 55 (7%) individual patient MDR-TB strains contained mutations in <it>gyrA </it>gene. The data advocate routine drug susceptibility testing for this important second-line drug for proper management of MDR-TB in Kuwait. Lack of mutations in 3'-end of <it>rrs </it>gene that confer resistance to injectable agents reduce the likelihood of occurrence of XDR-TB, at present, in Kuwait.</p> |
| first_indexed | 2024-12-11T01:47:29Z |
| format | Article |
| id | doaj.art-fa929658d41b40f09fcd767321345884 |
| institution | Directory Open Access Journal |
| issn | 1756-0500 |
| language | English |
| last_indexed | 2024-12-11T01:47:29Z |
| publishDate | 2011-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Research Notes |
| spelling | doaj.art-fa929658d41b40f09fcd7673213458842022-12-22T01:24:52ZengBMCBMC Research Notes1756-05002011-04-014112310.1186/1756-0500-4-123First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in KuwaitAhmad SuhailAl-Mutairi Noura MMokaddas Eiman<p>Abstract</p> <p>Background</p> <p>Nearly 5% of all <it>Mycobacterium tuberculosis </it>strains worldwide are resistant at least to rifampicin and isoniazid (multidrug-resistant tuberculosis, MDR-TB). Inclusion of a fluoroquinolone and an injectable agent (kanamycin, amikacin or capreomycin) in multidrug therapy is crucial for proper treatment of MDR-TB. The incidence of MDR-TB in Kuwait is ~1%. MDR-TB strains additionally resistant to fluoroquinolones and injectable agents are defined as extensively drug-resistant (XDR-TB) strains and have been detected in >55 countries. Infections with XDR-TB strains have very poor prognosis. This study detected the occurrence of <it>gyrA </it>mutations associated with fluoroquinolone resistance among MDR-TB strains in Kuwait.</p> <p>Findings</p> <p>Direct DNA sequencing of quinolone resistance-determining region of <it>gyrA </it>gene was performed to detect fluoroquinolone resistance-associated mutations in 85 MDR-TB strains isolated from 55 TB patients and 25 pansusceptible <it>M. tuberculosis </it>strains. For isolates exhibiting <it>gyrA </it>mutations, 3'-end of <it>rrs </it>(16S rRNA) was sequenced for the detection of XDR-TB. Fingerprinting of fluoroquinolone resistant MDR-TB strains was performed by detecting mutations in three (81 bp hot-spot, N-terminal and cluster II) regions of <it>rpoB</it>, <it>katG </it>codon 315 and <it>inhA</it>-regulatory region, polymorphisms at <it>gyrA </it>codon 95 and <it>katG </it>codon 463 by DNA sequencing and by double-repetitive-element PCR for determining strain relatedness. None of the pansusceptible but six of 85 MDR-TB strains contained <it>gyrA </it>mutations. Only <it>gyrA </it>codon 94 was mutated in all six (D94A in one and D94G in five) strains. Three of six mutant strains were recovered from the same patient while three other strains represented individual patient isolates. Fingerprinting studies identified all individual patient isolates as epidemiologically distinct strains. All six strains with a <it>gyrA </it>mutation contained wild-type <it>rrs </it>sequence.</p> <p>Conclusions</p> <p>Although fluoroquinolones are generally not used for chemotherapy of TB and drug susceptibility testing for second-line drugs is not carried out in Kuwait, four of 55 (7%) individual patient MDR-TB strains contained mutations in <it>gyrA </it>gene. The data advocate routine drug susceptibility testing for this important second-line drug for proper management of MDR-TB in Kuwait. Lack of mutations in 3'-end of <it>rrs </it>gene that confer resistance to injectable agents reduce the likelihood of occurrence of XDR-TB, at present, in Kuwait.</p>http://www.biomedcentral.com/1756-0500/4/123<it>M. tuberculosis</it>Fluoroquinolone resistance<it>gyrA </it>mutationsKuwait |
| spellingShingle | Ahmad Suhail Al-Mutairi Noura M Mokaddas Eiman First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in Kuwait BMC Research Notes <it>M. tuberculosis</it> Fluoroquinolone resistance <it>gyrA </it>mutations Kuwait |
| title | First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in Kuwait |
| title_full | First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in Kuwait |
| title_fullStr | First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in Kuwait |
| title_full_unstemmed | First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in Kuwait |
| title_short | First report of molecular detection of fluoroquinolone resistance-associated <it>gyrA </it>mutations in multidrug-resistant clinical <it>Mycobacterium tuberculosis </it>isolates in Kuwait |
| title_sort | first report of molecular detection of fluoroquinolone resistance associated it gyra it mutations in multidrug resistant clinical it mycobacterium tuberculosis it isolates in kuwait |
| topic | <it>M. tuberculosis</it> Fluoroquinolone resistance <it>gyrA </it>mutations Kuwait |
| url | http://www.biomedcentral.com/1756-0500/4/123 |
| work_keys_str_mv | AT ahmadsuhail firstreportofmoleculardetectionoffluoroquinoloneresistanceassociateditgyraitmutationsinmultidrugresistantclinicalitmycobacteriumtuberculosisitisolatesinkuwait AT almutairinouram firstreportofmoleculardetectionoffluoroquinoloneresistanceassociateditgyraitmutationsinmultidrugresistantclinicalitmycobacteriumtuberculosisitisolatesinkuwait AT mokaddaseiman firstreportofmoleculardetectionoffluoroquinoloneresistanceassociateditgyraitmutationsinmultidrugresistantclinicalitmycobacteriumtuberculosisitisolatesinkuwait |