Rapid, accurate determination of multidrug resistance in M. tuberculosis isolates and sputum using a biochip system.
OBJECTIVE
To develop and evaluate a rapid biochip system for the determination of multidrug-resistant tuberculosis (MDR-TB) in Mycobacterium tuberculosis isolates and clinical sputum samples.


METHODS
We developed a total solution-based system, including a biochip kit, apparatus for sample preparation, hybridisation, washing and data acquisition, and dedicated software for automated diagnosis. The biochip simultaneously identifies M. tuberculosis and detects the most commonly found mutations in the rpoB, katG and inhA genes. The system was assessed with 330 mycobacterial isolates and 129 sputum samples for rifampicin (RMP), and with 205 isolates and 105 sputum samples for isoniazid (INH), and then compared to DNA sequencing and conventional drug susceptibility testing (DST).


RESULTS
The entire biochip assay took 6 h. The concordance rate between the biochip assay and the DNA sequencing results was 100%. Compared to conventional DST, the concordance rates were 91.8% for isolates and 94.6% for sputum samples for RMP resistance, and 70.2% for isolates and 78.1% for sputum samples for INH resistance.


CONCLUSIONS
The biochip system provides a simple, rapid, reliable and accurate clinical assay for the parallel detection of M. tuberculosis and prevalent MDR-TB in a 6 h procedure, using either culture isolates or sputum samples for diagnosis.
Guo
Y
Y
Medical Systems Biology Research Centre, Tsinghua University, Beijing, China.
Zhou
Y
Y
Wang
C
C
Zhu
L
L
Wang
S
S
Li
Q
Q
Jiang
G
G
Zhao
B
B
Huang
H
H
Yu
H
H
Xing
W
W
Mitchelson
K
K
Cheng
Jing
J
Zhao
Yanlin
Y
D000995:Antitubercular Agents / Q000494:pharmacology*; D015374:Biosensing Techniques / Q000295:instrumentation*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D013183:Sputum / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000235:genetics
D000995:Antitubercular Agents