Publication: Whole-genome analysis of drug-resistant Mycobacterium tuberculosis reveals novel mutations associated with fluoroquinolone resistance
Issued Date
2021-09-01
Resource Type
ISSN
18727913
09248579
09248579
Other identifier(s)
2-s2.0-85110541503
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Antimicrobial Agents. Vol.58, No.3 (2021)
Suggested Citation
Pratchakan Chaiyachat, Angkana Chaiprasert, Ditthawat Nonghanphithak, Saijai Smithtikarn, Phalin Kamolwat, Petchawan Pungrassami, Wipa Reechaipichitkul, Rick Twee Hee Ong, Yik Ying Teo, Kiatichai Faksri Whole-genome analysis of drug-resistant Mycobacterium tuberculosis reveals novel mutations associated with fluoroquinolone resistance. International Journal of Antimicrobial Agents. Vol.58, No.3 (2021). doi:10.1016/j.ijantimicag.2021.106385 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77917
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Title
Whole-genome analysis of drug-resistant Mycobacterium tuberculosis reveals novel mutations associated with fluoroquinolone resistance
Abstract
Multidrug-resistant and extensively drug-resistant tuberculosis (M/XDR-TB) remains a global public-health challenge. Known mutations in quinolone resistance-determination regions cannot fully explain phenotypic fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb). The aim of this study was to look for novel mutations in Mtb associated with resistance to FQ drugs using whole-genome sequencing analysis. Whole-genome sequences of 659 Mtb strains, including 214 with phenotypic FQ resistance and 445 pan-susceptible isolates, were explored for mutations associated with FQ resistance overall and with resistance to individual FQ drugs (ofloxacin, levofloxacin, moxifloxacin and gatifloxacin). Three novel genes (recC, Rv2005c and PPE59) associated with FQ resistance were identified (P < 0.00001 based on screening analysis and absence of relevant mutations in a pan-susceptible validation set of 360 strains). Nine novel single nucleotide polymorphisms (SNPs), including in gyrB (G5383A and G6773A), gyrA (G7892A), recC (G725900C and G726857T/C), Rv2005c (C2251373G, G2251420C and C2251725T) and PPE59 (C3847269T), were used for diagnostic performance analysis. Enhancing the known SNP set with five of these novel SNPs, including gyrA [G7892A (Leu247Leu)], recC [G725900C (Leu893Leu) and G726857T/C (Arg484Arg)], Rv2005c [G2251420C (Pro205Arg)] and PPE59 [C3847269T (Asn35Asn)] increased the sensitivity of detection of FQ-resistant Mtb from 83.2% (178/214) to 86.9% (186/214) while maintaining 100% specificity (360/360). No specific mutation associated with resistance to only a single drug (ofloxacin, levofloxacin, moxifloxacin or gatifloxacin) was found. In conclusion, this study reports possible additional mutations associated with FQ resistance in Mtb.