Frequency and Geographic Distribution of gyrA and gyrB Mutations Associated with Fluoroquinolone Resistance in Clinical Mycobacterium Tuberculosis Isolates: A Systematic Review

Avalos, Elisea Estela; Catanzaro, Donald G.; Catanzaro, Antonino; Ganiats, Théodore G.; Brodine, Stephanie K.; Alcaraz, John E.; Rodwell, Timothy C.

doi:10.1371/journal.pone.0120470

Cited by 118 publications

(126 citation statements)

References 67 publications

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“…The codon 90 mutation A90V has also been found at a high frequency; studies from India, the Philippines, China, and Belgium have reported it as the most common mutation (23,24,35,42). The review by Avalos et al found that A90V accounted for 13 to 20% of mutations contributing to resistance (32). In the present study, D94G and A90V were the most commonly observed mutations.…”

Section: Figsupporting

confidence: 58%

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Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

et al. 2016

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h Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in the gyrA and gyrB genes of Mycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in the gyrA and gyrB genes of acid-fast bacillus (AFB) smear-positive sediments or of M. tuberculosis isolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of the gyrA and gyrB genes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in the gyrA genes of 25 strains, while no mutations were observed in the gyrB genes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. The gyrA mutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis.T reatment of multidrug-resistant tuberculosis (MDR-TB) patients, with strains resistant to rifampin (RIF) and isoniazid (INH), is further complicated by the presence of fluoroquinolone (FQ) resistance, due to prolonged, limited, and expensive treatment options (1, 2). A recent meta-analysis of the responses to treatment of 6,724 MDR-TB patients from 26 centers revealed that the frequency of treatment success was 64%, while that for patients with MDR-TB plus FQ resistance was only 48% (3). This clearly indicates the need for routine molecular screening for FQ resistance-associated molecular markers so that the treatment of such patients can be optimized without delay. Many such patients develop extensively drug resistant tuberculosis (XDR-TB), defined as MDR-TB plus resistance to any one FQ and any of the aminoglycosides/cyclic peptides (A-CP) (4). This poses an even more serious threat to TB management, since only 40% of XDR-TB patients have successful treatment outcomes (2). Previous studies have suggested that 5.4% (95% confidence interval [95% CI], 3.4 to 7.5%) of MDR-TB cases may actually be XDR-TB (2).FQs are oral antibacterial agents that have activity against Mycobacterium tuberculosis (5, 6). Hence, FQs are recommended for the treatment of MDR-TB patients and patients with intolerance to RIF (2). FQs are also being evaluated in ...

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Section: Figsupporting

confidence: 58%

“…In another review, across 18 countries, by Avalos et al, mutation data for 3,846 clinical isolates with known profiles of phenotypic resistance to FQ were studied. The most frequent gyrA mutation was D94G, which ranged from 21 to 32% (32). The relative frequencies of QRDR mutations reported from different regions worldwide are detailed in Table 2.…”

Section: Figmentioning

confidence: 99%

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

et al. 2016

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“…However, in our study, the results showed no significant association between ofloxacin resistance and gyrA mutations, and also, kanamycin resistance and rrs mutations. Based on the correlation studies among these primers, genetic and the geographic distances should be evaluated in a future study [14]. Table 3.…”

Section: Discussionmentioning

confidence: 99%

“…Related studies have shown specificities of gene mutations in predicting kanamycin [9] [10] [11] and ofloxacin resistance [11] [12] [13] [14]. Many studies have been conducted on genotypic and phenotypic characteristics of drug resistant M. tuberculosis; however, this kind of study is rare in Thailand [15].…”

Section: Xdr-tb Normally Develops From Multi-drug Resistant Tuberculomentioning

confidence: 99%

“…One related study showed that gyrA mutations at positions 88 to 94 had a high level of ofloxacin resistance [20], especially gyrA 94 that exhibited high level of resistance to moxifloxacin and gatifloxam [21]. Some studies found that mutations in gyrA at codons 21, 95, and 668 were not associated with ofloxacin resistance [14]. Only gyrA mutation at codon 95 could be detected by commercial molecular tests [20].…”

Section: Ofloxacin Resistancementioning

confidence: 99%

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Correlations between Gene Resistant Markers and Second-Line Anti-TB Drug Resistance in Pre-XDR and XDR-TB Patients

Jaksuwan¹,

Tharavichikul²,

Chuchottaworn³

et al. 2017

JTR

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Background: Extensively drug resistant tuberculosis (XDR-TB) is a serious problem in public health and XDR-TB patients usually develop from multi-drug resistance tuberculosis (MDR-TB) and pre-XDR-TB. The rapid molecular test for drug susceptibility testing (DST) can be used for early detection to prevent XDR-TB. Methods: We examined 34 clinical Mycobacterium tuberculosis (M. tuberculosis) isolates from MDR/XDR-TB patients in the upper north of Thailand that were identified with drug susceptibility profiles by indirect agar proportion method from 2005-2012. Our study investigated the genetic mutations in gyrA for ofloxacin resistance and rrs for kanamycin resistance. The genetic mutations and drug susceptibility test results were analyzed using the exact test. Results: The majority of the ofloxacin resistance was detected in gyrA 21, gyrA 70, gyrA 87, gyrA 102, gyrA 162, and gyrA 187 were at 0%, 12.5%, 37.5%, 0%, 50.0% and 25.0% sensitivity, respectively, and at 96.2, 96.2%, 20.1%, 96.2%, 57.7% and 61.5% specificity, respectively. Kanamycin resistance was found in rrs 512, rrs 241, rrs 223, rrs 414 and rrs 408 at 16.7%, 0%, 0%, 16.7% and 16.7% sensitivity, respectively, and at 96.4%, 92.9%, 82.1%, 82.1% and 71.4% specificity, respectively. This study found no significant correlation between gyrA mutations and ofloxacin resistance and also no correlation between the rrs gene and kanamycin resistance. Conclusion: These primer sequences and PCR products in our study such as gyrA and rrs might be unsuitable to detect ofloxacin and kanamycin resistance in the upper How to cite this paper:

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Potent Inhibition of Bacterial DNA Gyrase by Digallic Acid and Other Gallate Derivatives

et al. 2022

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Bacterial DNA gyrase, an essential enzyme, is a validated target for discovering and developing new antibiotics. Here we screened a pool of polyphenols and discovered that digallic acid is a potent DNA gyrase inhibitor. We also found that several food additives based on gallate, such as dodecyl gallate, potently inhibit bacterial DNA gyrase. Interestingly, the IC50 of these gallate derivatives against DNA gyrase is correlated with the length of hydrocarbon chain connecting to the gallate. These new bacterial DNA gyrase inhibitors are ATP competitive inhibitors of DNA gyrase. Our results also show that digallic acid and certain gallate derivatives potently inhibit E. coli DNA topoisomerase IV. Several gallate derivatives have strong antimicrobial activities against Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus (MRSA). This study provides a solid foundation for the design and synthesis of gallate‐based DNA gyrase inhibitors that may be used to combat antibacterial resistance.

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Frequency and Geographic Distribution of gyrA and gyrB Mutations Associated with Fluoroquinolone Resistance in Clinical Mycobacterium Tuberculosis Isolates: A Systematic Review

Cited by 118 publications

References 67 publications

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

Correlations between Gene Resistant Markers and Second-Line Anti-TB Drug Resistance in Pre-XDR and XDR-TB Patients

Potent Inhibition of Bacterial DNA Gyrase by Digallic Acid and Other Gallate Derivatives

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