Abstract
During the early development of drug resistance in Mycobacterium tuberculosis (M. tuberculosis) infection only a small proportion of resistant bacteria are present within a milieu of sensitive bacteria. This complicates the use of molecular methods to predict the presence of a resistant phenotype and has been largely ignored in many of the newly developed molecular methods. In this study, mixtures of DNA from M. tuberculosis strains with known wild-type and mutant sequences were used to evaluate the sensitivity of three different molecular methods for detection of drug resistance. The dot-blot and amplification refractory mutation system (ARMS) methods showed sensitivities that approach those of routine phenotypic methods and are able to detect the presence of mutant sequences at a ratio of 1 in 50 (corresponding to 2% mutant sequences). This is 10-fold more sensitive than the commercial kit. The ARMS method was also used to investigate the use of molecular methods to identify mixed infections, and both drug-resistant and susceptible strain populations were identified in a single clinical isolate. These findings highlight the applicability of molecular methods to the rapid detection of drug resistance in tuberculosis patients, particularly in those who are non-compliant and in contacts of known drug-resistant tuberculosis patients, and assistance in limiting the spread of drug-resistant strains.
| Original language | English |
|---|---|
| Pages (from-to) | 876-881 |
| Number of pages | 6 |
| Journal | Clinical Chemistry and Laboratory Medicine |
| Volume | 40 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2002 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Clinical Biochemistry
- Biochemistry, medical
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Molecular detection of early appearance of drug resistance during Mycobacterium tuberculosis infection. / Victor, Thomas C.; Lee, Hyeyoung; Cho, Sangnae; Jordaan, Annemarie M.; van der Spuy, Gian; van Helden, Paul D.; Warren, Robin.
In: Clinical Chemistry and Laboratory Medicine, Vol. 40, No. 9, 01.01.2002, p. 876-881.Research output: Contribution to journal › Article
TY - JOUR
T1 - Molecular detection of early appearance of drug resistance during Mycobacterium tuberculosis infection
AU - Victor, Thomas C.
AU - Lee, Hyeyoung
AU - Cho, Sangnae
AU - Jordaan, Annemarie M.
AU - van der Spuy, Gian
AU - van Helden, Paul D.
AU - Warren, Robin
PY - 2002/1/1
Y1 - 2002/1/1
N2 - During the early development of drug resistance in Mycobacterium tuberculosis (M. tuberculosis) infection only a small proportion of resistant bacteria are present within a milieu of sensitive bacteria. This complicates the use of molecular methods to predict the presence of a resistant phenotype and has been largely ignored in many of the newly developed molecular methods. In this study, mixtures of DNA from M. tuberculosis strains with known wild-type and mutant sequences were used to evaluate the sensitivity of three different molecular methods for detection of drug resistance. The dot-blot and amplification refractory mutation system (ARMS) methods showed sensitivities that approach those of routine phenotypic methods and are able to detect the presence of mutant sequences at a ratio of 1 in 50 (corresponding to 2% mutant sequences). This is 10-fold more sensitive than the commercial kit. The ARMS method was also used to investigate the use of molecular methods to identify mixed infections, and both drug-resistant and susceptible strain populations were identified in a single clinical isolate. These findings highlight the applicability of molecular methods to the rapid detection of drug resistance in tuberculosis patients, particularly in those who are non-compliant and in contacts of known drug-resistant tuberculosis patients, and assistance in limiting the spread of drug-resistant strains.
AB - During the early development of drug resistance in Mycobacterium tuberculosis (M. tuberculosis) infection only a small proportion of resistant bacteria are present within a milieu of sensitive bacteria. This complicates the use of molecular methods to predict the presence of a resistant phenotype and has been largely ignored in many of the newly developed molecular methods. In this study, mixtures of DNA from M. tuberculosis strains with known wild-type and mutant sequences were used to evaluate the sensitivity of three different molecular methods for detection of drug resistance. The dot-blot and amplification refractory mutation system (ARMS) methods showed sensitivities that approach those of routine phenotypic methods and are able to detect the presence of mutant sequences at a ratio of 1 in 50 (corresponding to 2% mutant sequences). This is 10-fold more sensitive than the commercial kit. The ARMS method was also used to investigate the use of molecular methods to identify mixed infections, and both drug-resistant and susceptible strain populations were identified in a single clinical isolate. These findings highlight the applicability of molecular methods to the rapid detection of drug resistance in tuberculosis patients, particularly in those who are non-compliant and in contacts of known drug-resistant tuberculosis patients, and assistance in limiting the spread of drug-resistant strains.
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UR - http://www.scopus.com/inward/citedby.url?scp=0036408718&partnerID=8YFLogxK
U2 - 10.1515/CCLM.2002.155
DO - 10.1515/CCLM.2002.155
M3 - Article
C2 - 12435103
AN - SCOPUS:0036408718
VL - 40
SP - 876
EP - 881
JO - Clinical Chemistry and Laboratory Medicine
JF - Clinical Chemistry and Laboratory Medicine
SN - 1434-6621
IS - 9
ER -