Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1994-10-12
1998-12-22
Horlick, Kenneth R.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 911, 435 912, 536 243, 536 2432, 536 253, 536 266, C12P 1934, C12Q 168, C07H 2104, C07H 2100
Patent
active
058517634
DESCRIPTION:
BRIEF SUMMARY
This application is a National stage application filed under 35 U.S.C. .sctn. 371 based on International Application PCT/EP/01063, filed Apr. 30, 1993, which is based upon U.S. application Ser. No. 07/929,206, filed Aug. 14, 1992, now U.S. Pat. No. 5,633,131, issued May 27, 1997, which is a continuation-in-part application of U.S. application Ser. No. 07/875,940, filed Apr. 30, 1992, now abandoned and French applications No. FR 93 04545, filed Apr. 16, 1993, and No. FR 92 11098, filed Sep. 17, 1992.
This invention relates to the rapid detection of strains of Mycobacterium tuberculosis that are resistant to antibiotics, particularly isoniazid, rifampicin and streptomycin. More particularly, this invention relates to a method of detecting antibiotic resistance in Mycobacterium tuberculosis, e.g. either as a result of mutations in the relevant genes or by nucleic acid hybridization. This invention also relates to a nucleic acid probe and a kit for carrying out the nucleic acid hybridization. The invention further relates to the chromosomal location of the katG gene (SEQ ID NO:45) and its nucleotide sequence.
BACKGROUND OF THE INVENTION
Despite more than a century of research since the discovery of Mycobacterium tuberculosis, the aetiological agent of tuberculosis, by Robert Koch, this disease remains one of the major causes of human morbidity and mortality. There are an estimated 3 million deaths annually attributable to tuberculosis (Snider, 1989), and although the majority of these are in developing countries, the disease is assuming renewed importance in the West due to the increasing number of homeless people and the impact of the AIDS epidemic (Chaisson et al., 1987; Snider and Roper, 1992).
Isonicotinic acid hydrazide or isoniazid (INH) has been used in the treatment of tuberculosis for the last forty years due to its exquisite potency against the members of the "tuberculosis" groups--Mycobacterium tuberculosis, M. bovis and M. africanum (Middlebrook, 1952; Youatt, 1969). Neither the precise target of the drug, nor its mode of action, are known, and INH treatment results in the perturbation of several metabolic pathways. There is substantial evidence indicating that INH may act as an antimetabolite of NAD and pyridoxal phosphate (Bekierkunst and Bricker, 1967; Sriprakash and Ramakrishnan, 1970; Winder and Collins, 1968, 1969, 1970), and other data indicating that the drug blocks the synthesis of the mycolic acids, which are responsible for the acid-fast character of mycobacterial cell walls (Winder and Collins 1970; Quemard et al., 1991). Shortly after its introduction, INH-resistant isolates of Mycobacterium tuberculosis emerged and, on characterization, were often found to have lost catalase-peroxidase activity and to show reduced virulence in guinea pigs (Middlebrook et al., 1954; Kubica et al., 1968; Sriprakash and Ramakrishnan, 1970).
Very recently, INH-resistance has acquired new significance owing to a tuberculosis epidemic in the USA due to multidrug resistant (MDR) variants of M. tuberculosis (CDC, 1990; 1991a, b) and the demonstration that such strains were responsible for extensive nosocomial infections of HIV-infected individuals and health care workers (Snider and Roper, 1992). In view of the gravity of this problem, there exists a need in the art to determine the relationship between INH-resistance and catalase-peroxidase production.
More particularly, there is a need in the art to understand the molecular mechanisms involved in drug sensitivity. In addition, there is a need in the art to develop a simple test permitting the rapid identification of INH-resistant strains. Further, there is a need in the art for reagents to carry out such a test.
Rifampicin too is a major antibiotic used for the treatment of infections by mycobacterium, particularly Mycobacterium tuberculosis and Mycobacterium leprae. Because some mycobacteria grow slowly, possible rapid and efficient tests for the testing of resistance to rifampicin or analogues thereof must be made available. Likewise the invention aims
REFERENCES:
patent: 4683195 (1987-07-01), Mullis et al.
patent: 5633131 (1997-05-01), Heym et al.
Heym et al. (1992), Research in Microbiology, vol. 143, No. 7, pp. 721-730.
Jin et al. (1988), Journal of Molecular Biology, vol. 202, No. 1, pp. 45-58.
Sriprakash et al. (1970), The Journal of General Microbiology, vol. 60, No. 1, pp. 125-132.
Telenti et al. (1993), The Lancet, vol. 341, No. 8846, pp. 647-650.
Zhang et al. (1992), Nature, vol. 358, No. 6387, pp. 591-593.
Bodmer Thomas
Cole Stewart
Heym Beate
Honore Nadine
Telenti Amalio
Horlick Kenneth R.
Institut Pasteur
Tung Joyce
LandOfFree
Rapid detection of antibiotic resistance in mycobacterium tuberc does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Rapid detection of antibiotic resistance in mycobacterium tuberc, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Rapid detection of antibiotic resistance in mycobacterium tuberc will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2045704