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Research article
Fluoroquinolone resistance and mutational profile of gyrA in pulmonary MDR tuberculosis patients
Abdul Rehman
University of the Punjab
Corresponding Author
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Background Fluoroquinolones (FQs) are potential drugs that inhibit DNA synthesis and are used in the treatment of multidrug-resistant tuberculosis (TB) and short-term anti-TB regimens. In recent years, a high proportion of FQ resistance has been observed in Mycobacterium tuberculosis isolates. The development of FQ resistance in multidrug-resistant TB negatively impacts patient treatment outcome and is a serious threat to control of TB.
Methods The study included a total of 562 samples from patients with pulmonary TB that had been on anti-tuberculosis therapy. MTBDRsl assays were performed for the molecular detection of mutations. Sequence analysis was performed for the characterization and mutational profiling of FQ-resistant isolates.
Results FQ resistance was observed in 104 samples (18.5%), most of which were previously treated and treatment failure cases. A total of 102 isolates had mutations in DNA gyrase subunit A (gyrA), while mutations in gyrB were observed in only two isolates. Mutational analysis revealed that the mutations mostly alter codons 94 (replacing aspartic acid with glycine, D94G) and 90 (replacing alanine with valine, A90V). In MDR and treatment failure cases, resistance to FQs was most commonly associated with the D94G mutation. In contract, a high proportion of A90V mutations were observed in isolates that were newly diagnosed.
Conclusion The findings suggest that genotypic assays for FQ resistance should be carried out at the time of initial diagnosis, before starting treatment, in order to rule out mutations that impact the potential use of FQs in treatment and to control drug resistance.
Keywords
Mycobacterium tuberculosis, MDR and pre-XDR TB, fluoroquinolone resistance, MTBDRsl assay
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On 03 Feb, 2020
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Editor invited
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On 16 Jan, 2020
Editor assigned
On 10 Jan, 2020
Submission checks complete
On 09 Jan, 2020
Editor invited
On 09 Jan, 2020
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Reviewer #2 agreed
On 13 Dec, 2019
Review #2 received
Received 13 Dec, 2019
Editorial decision: Major revision
On 13 Dec, 2019
Review #1 received
Received 07 Nov, 2019
Editor assigned
On 22 Oct, 2019
Reviewers invited
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Reviewer #1 agreed
On 22 Oct, 2019
Submission checks complete
On 03 Oct, 2019
Editor invited
On 03 Oct, 2019
First submitted
On 23 Sep, 2019
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Subject Areas
Pulmonology
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This preprint is under consideration at BMC Pulmonary Medicine. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Fluoroquinolone resistance and mutational profile of gyrA in pulmonary MDR tuberculosis patients
Abdul Rehman
University of the Punjab
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 4
Posted 16 Apr, 2020
No community comments so far
Editor assigned
On 13 Apr, 2020
Submission checks complete
On 12 Apr, 2020
Editor invited
On 12 Apr, 2020
No comments provided
Editorial decision: Major revision
On 17 Mar, 2020
Editor assigned
On 03 Feb, 2020
Submission checks complete
On 02 Feb, 2020
Editor invited
On 02 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 16 Jan, 2020
Editor assigned
On 10 Jan, 2020
Submission checks complete
On 09 Jan, 2020
Editor invited
On 09 Jan, 2020
No comments provided
Reviewer #2 agreed
On 13 Dec, 2019
Review #2 received
Received 13 Dec, 2019
Editorial decision: Major revision
On 13 Dec, 2019
Review #1 received
Received 07 Nov, 2019
Editor assigned
On 22 Oct, 2019
Reviewers invited
Invitations sent on 22 Oct, 2019
Reviewer #1 agreed
On 22 Oct, 2019
Submission checks complete
On 03 Oct, 2019
Editor invited
On 03 Oct, 2019
First submitted
On 23 Sep, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pulmonology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background Fluoroquinolones (FQs) are potential drugs that inhibit DNA synthesis and are used in the treatment of multidrug-resistant tuberculosis (TB) and short-term anti-TB regimens. In recent years, a high proportion of FQ resistance has been observed in Mycobacterium tuberculosis isolates. The development of FQ resistance in multidrug-resistant TB negatively impacts patient treatment outcome and is a serious threat to control of TB.
Methods The study included a total of 562 samples from patients with pulmonary TB that had been on anti-tuberculosis therapy. MTBDRsl assays were performed for the molecular detection of mutations. Sequence analysis was performed for the characterization and mutational profiling of FQ-resistant isolates.
Results FQ resistance was observed in 104 samples (18.5%), most of which were previously treated and treatment failure cases. A total of 102 isolates had mutations in DNA gyrase subunit A (gyrA), while mutations in gyrB were observed in only two isolates. Mutational analysis revealed that the mutations mostly alter codons 94 (replacing aspartic acid with glycine, D94G) and 90 (replacing alanine with valine, A90V). In MDR and treatment failure cases, resistance to FQs was most commonly associated with the D94G mutation. In contract, a high proportion of A90V mutations were observed in isolates that were newly diagnosed.
Conclusion The findings suggest that genotypic assays for FQ resistance should be carried out at the time of initial diagnosis, before starting treatment, in order to rule out mutations that impact the potential use of FQs in treatment and to control drug resistance.
Figure 1
Figure 2