title: Tuberculosis-spoligo-rifampin-isoniazid typing: an all-in-one assay technique for surveillance and control of multidrug-resistant tuberculosis on Luminex devices.
abstract: As a follow-up of the "spoligoriftyping" development, we present here an extension of this technique which includes the detection of isoniazid resistance-associated mutations in a new 59-plex assay, i.e., tuberculosis-spoligo-rifampin-isoniazid typing (TB-SPRINT), running on microbead-based multiplexed systems. This assay improves the synergy between clinical microbiology and epidemiology by providing (i) mutation-based prediction of drug resistance profiles for patient treatment and (ii) genotyping data for tuberculosis (TB) surveillance. This third-generation microbead-based high-throughput assay for TB runs on the Luminex 200 system and on the recently launched MagPix system (Luminex, Austin, TX). Spoligotyping patterns obtained by the TB-SPRINT method were 100% (n = 85 isolates; 3,655/3,655 spoligotype data points) concordant with those obtained by microbead-based and membrane-based spoligotyping. Genetic drug susceptibility typing provided by the TB-SPRINT method was 100% concordant with resistance locus sequencing (n = 162 for rpoB gene sequencing and n = 76 for katG and inhA sequencing). Considering phenotypic drug susceptibility testing (DST) as the reference method, the sensitivity and specificity of TB-SPRINT regarding Mycobacterium tuberculosis complex (n = 162 isolates) rifampin resistance were both 100%, and those for isoniazid resistance were 90.4% (95% confidence interval, 85 to 95%) and 100%, respectively. Used routinely in national TB reference and specialized laboratories, the TB-SPRINT assay should simultaneously improve personalized medicine and epidemiological surveillance of multidrug-resistant (MDR) TB. This assay is expected to play an emerging role in public health in countries with heavy burdens of MDR TB and/or HIV/TB coinfection. Application of this assay directly to biological samples, as well as development for extensively drug-resistant (XDR) TB detection by inclusion of second-line antituberculosis drug-associated mutations, is under development. With bioinformatical methods and data mining to reduce the number of targets to the most informative ones, locally adapted formats of this technique can easily be developed everywhere.
authors: Institut de Génétique et Microbiologie, UMR8621, CNRS-Université Paris-Sud, Paris, France.
authors: Michel Kiréopori
authors: MK
authors: Gomgnimbou
authors: Iván
authors: I
authors: Hernández-Neuta
authors: Stefan
authors: S
authors: Panaiotov
authors: Elizabeta
authors: E
authors: Bachiyska
authors: Juan Carlos
authors: JC
authors: Palomino
authors: Anandi
authors: A
authors: Martin
authors: Patricia
authors: P
authors: del Portillo
authors: Guislaine
authors: G
authors: Refregier
authors: Christophe
authors: C
authors: Sola
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D062665:Epidemiological Monitoring; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D017720:Molecular Epidemiology / Q000379:methods; D058889:Molecular Typing / Q000379:methods*; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D057285:Precision Medicine / Q000379:methods; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D007538:Isoniazid; D012293:Rifampin
references: J Clin Microbiol. 2013 May;51(5):1596-9
references: 23447641
references: BMC Infect Dis. 2008 Jan 25;8:10
references: 18221534
references: Mol Microbiol. 2011 Dec;82(6):1375-91
references: 22026918
references: Emerg Infect Dis. 2012 Jan;18(1):117-9
references: 22257494
references: Antimicrob Agents Chemother. 1996 Nov;40(11):2655-7
references: 8913484
references: Clin Microbiol Rev. 1995 Oct;8(4):496-514
references: 8665467
references: Nat Commun. 2012 Mar 20;3:753
references: 22434196
references: Thorax. 2013 Mar;68(3):283-7
references: 23321600
references: World Health Forum. 1993;14(4):438
references: 8185806
references: BMC Microbiol. 2009 Jan 15;9:10
references: 19146699
references: Hum Immunol. 2005 May;66(5):501-12
references: 15935887
references: J Biol Chem. 2012 Aug 10;287(33):27743-52
references: 22648414
references: J Bacteriol. 2000 May;182(9):2393-401
references: 10762237
references: J Bacteriol. 1999 Feb;181(4):1343-7
references: 9973365
references: J Antimicrob Chemother. 2009 Aug;64(2):263-6
references: 19520719
references: Infect Genet Evol. 2012 Jun;12(4):678-85
references: 21867778
references: J Clin Microbiol. 2012 Dec;50(12):3831-7
references: 22972833
references: Arch Pathol Lab Med. 1995 Feb;119(2):131-8
references: 7848059
references: BMC Microbiol. 2006 Mar 06;6:23
references: 16519816
references: J Infect Dis. 1996 Jan;173(1):196-202
references: 8537659
references: J Mol Model. 2012 Sep;18(9):4013-24
references: 22460521
references: J Clin Microbiol. 1997 Apr;35(4):907-14
references: 9157152
references: PLoS One. 2012;7(8):e43240
references: 22916230
references: J Clin Microbiol. 2010 Dec;48(12):4386-91
references: 20881173
references: PLoS Med. 2009 Feb 10;6(2):e2
references: 19209951
references: BMC Microbiol. 2012 May 30;12:90
references: 22646308
references: J Clin Microbiol. 2013 Jul;51(7):2232-7
references: 23658258
references: J Antimicrob Chemother. 2009 Aug;64(2):259-62
references: 19520715
references: J Clin Microbiol. 2012 Oct;50(10):3172-9
references: 22814456
references: Emerg Infect Dis. 2013 Mar;19(3):460-3
references: 23622814
references: J Clin Microbiol. 1991 Nov;29(11):2578-86
references: 1685494
references: J Clin Microbiol. 1994 Apr;32(4):1095-8
references: 8027320
references: Mutat Res. 2011 Jul 1;712(1-2):33-9
references: 21514309
references: J Med Microbiol. 2010 Mar;59(Pt 3):285-294
references: 19959631
references: Lancet. 2011 Apr 30;377(9776):1495-505
references: 21507477
references: Nature. 1992 Aug 13;358(6387):591-3
references: 1501713
references: J Clin Microbiol. 2007 Aug;45(8):2635-40
references: 17537937
references: Antimicrob Agents Chemother. 1993 Oct;37(10):2054-8
references: 8257122
references: Bioinformatics. 2002 Feb;18(2):235-43
references: 11847071
references: PLoS One. 2012;7(5):e36995
references: 22623967
references: Int J Tuberc Lung Dis. 2002 Nov;6(11):959-65
references: 12475141
references: J Clin Microbiol. 2012 Mar;50(3):696-701
references: 22205819
references: Trop Med Int Health. 2013 Jan;18(1):109-16
references: 23170876
references: Tuber Lung Dis. 1995 Oct;76(5):425-30
references: 7496004