• resize text resize text

DNA Chips: A New Approach for Genotyping Mycobacteria

Santa Clara (CA), USA and Marcy l'Etoile, France - January 11, 1999. In the January issue of the Journal of Clinical Microbiology, Alain Troesch (bioMérieux, Inc.) et al.1 show for the first time that a high density GeneChip® array (Affymetrix, Inc.) makes it possible to genotype all mycobacteria species of clinical importance, including species which are members of the M. tuberculosis complex and atypical mycobacteria.

Identifying the Species and Determining Their Resistance Profile
The genus Mycobacterium is made up of approximately 80 species and sub-species of bacteria. Among the pathogenic species, ten or so are responsible for 90% of mycobacterial diseases occurring in humans.

Tuberculosis is the most important of these diseases. It is caused by species in the Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis, and M. africanum). The other diseases are caused by opportunistic infections, especially in immunosuppressed individuals, involving a total of more than ten so-called atypical mycobacteria. These include M. xenopi and M. kansasii, which cause pulmonary, lymph node, osteoarticular, cutaneous and subcutaneous disorders, and species in the Mycobacterium avium-intracellulare complex, which cause generalized infections in AIDS patients.

In the research they present in this article, Alain Troesch and his colleagues used the same DNA chip (GeneChip array) to answer two questions in the biological diagnosis of mycobacterial infections simultaneously: they identified the mycobacterial species and determined its resistance to rifampin (the reference antibiotic included in the triple drug therapy recommended as the "first choice" treatment of tuberculosis). In light of the emergence of multi-resistant strains, the answers to these questions have become critical for the immediate administration of a properly adapted treatment.
The species identification of mycobacteria is based on the genetic typing of a highly polymorphic region, the 16S rRNA region. Several commercially available molecular diagnostic tests use this region, which is considered the "gold standard" of mycobacterial species specificity. By analyzing it researchers can identify the genetic fingerprint of the mycobacterium in question.

A similar approach may be followed to determine the rifampin resistance of species in the M. tuberculosis complex. In 90% of rifampin-resistant isolates, resistance has been shown to be conferred by highly localized mutations found in the region of the gene that codes for a bacterial RNA polymerase, the rpoB gene.

Troesch and his team amplified these two regions using reference collection mycobacterial isolates. The amplified genetic material was then subjected to fluorescent labeling and hybridized to oligonucleotide-specific probes on the surface of the GeneChip array. These probes, which the researchers divided into distinct areas on the chip, were identified according to their location.

This methodological approach obtained 100% reliability for each of the desired responses. Seventy strains representing 27 different mycobacterial species of clinical relevance were tested. The sequences of all the species were correctly identified. Moreover, among the M. tuberculosis strains tested, the 15 rifampin-resistant strains were correctly identified as such. The study also confirmed the GeneChip array’s high resolution specificity, since the chip detected resistance due to point mutations (those involving only one nucleotide change) as well as resistance involving more than one nucleotide change.

High Resolution Technology
The DNA chip technology developed by Fodor et al.2&3 of Affymetrix, Inc. (NASDAQ: AFFX) enables the production of a "biochip" designed to identify fluorescent-labeled DNA or RNA fragments through their hybridization to oligonucleotide probes, which are short DNA sequences. With the GeneChip array developed by Affymetrix, Inc. (NASDAQ: AFFX) the oligonucleotide probes are synthesized in situ using a technique that combines chemical synthesis on a glass substrate and photolithography. This technique, the fruit of microelectronics, is similar to the technique used for engraving. Using stencil-like masks, specific zones on the chip are exposed to or protected from the light in order to make photosensitive chemical groups react.

The miniaturized glass substrate measures approximately 1 cm2, which acts as the hybridization surface. Each hybridization surface may contain a very large number of unique oligonucleotide probes (up to 400,000), permitting several thousand individual nucleotide positions to be characterized at the same time. All nucleotide possibilities for each base position is represented on the array. A positive hybridization result is detected by the intensity of the fluorescence, which reflects the stability of the hybridization between the oligonucleotide probe and the target sequence.
Each probe is identified according to its position on the chip. Two sets of oligonucleotide probes are represented among the sequences arranged on the chip designed by Troesch and his colleagues: a species-specific set of probes (the region of the 16S ribosomal RNA), and probes used to detect mutations which may cause rifampin resistance (the region of the rpoB gene).

Several Responses on A Single Chip
There are two approaches for diagnosing a mycobacterial infection. The conventional approach consists of examining a sample under a microscope; bacterial culture; and the identification of the bacteria’s metabolites. The molecular approach involves recognizing the microorganism’s genetic fingerprint.

The conventional approach, which until recently was the only method available, has one major drawback: for some mycobacterial species it may take three to four weeks before culture results are obtained. This approach is gradually being replaced by the molecular method, which consists of identifying mycobacteria through genotyping. Several tests of this kind have been marketed recently. These tests, which generate results in four to five hours, have considerably reduced the waiting period before appropriate therapy can be administered, in addition to isolation of the patient, if necessary. They may be performed directly on a biological sample if the initial microscopic examination is positive (i.e., there is a sufficient quantity of bacteria in the sample). If this examination is negative, the genotyping methods require amplification by culturing or by enzymatic nucleic acid amplification of the genetic material.

The GeneChip array technology not only speeds up diagnosis, it also features two additional advantages not offered by other molecular techniques: its resolution power and the parallel running of several diagnostic tests. Its high resolution power means that, unlike other molecular tests that identify only the most common mycobacterial pathogens, it detects many more of the pathogenic mycobacterial species in humans. Due to the emergence of atypical mycobacteria that can cause opportunistic infections, the precise identification of each species is necessary. Such information will not only lead to improved treatment for these infections; it will also improve epidemiological knowledge of atypical mycobacteria, in particular their distribution in the environment.

Thanks to the new possibilities offered by the chip, multiple diagnostic parameters are now being contemplated. Specifically, there are plans to include on the chip, markers for resistance to other antibiotics whose molecular bases are gradually being determined. For example, isoniazid resistance was recently shown to be associated with mutations in the catalase-peroxidase gene (katG), in the promoter region of the inhA and ahpC genes, and in the kasA protein gene. Similarly, resistance to pyrazinamide seems to be associated with mutations in the pncA gene and resistance to ethambutol with the emb gene.

Successful Agreement Between bioMérieux and Affymetrix
The results obtained by Alain Troesch and his colleagues mark an important step toward fulfilling the objectives set by Affymetrix, Inc. (NASDAQ: AFFX) and bioMérieux in accordance with the terms of their collaboration agreement.
This agreement, which was concluded on October 21, 1996, and expanded on January 21, 1998, provides for the development of diagnostic tests based on the GeneChip array technique developed by Affymetrix, Inc. (NASDAQ: AFFX). It should allow bioMérieux to market a fully automated diagnostic system. The main target area for the product is infectious bacteriology, which is the focus of an exclusive agreement. Two other areas are also concerned: genotyping HIV strains that are resistant to antiretroviral treatments, and genotyping microbial contaminants affecting the food and cosmetic industries.

Anaïsä , a bioMérieux project that resulted from the agreement, will lead to the development of two reagents in the near future: a DNA chip for the identification of mycobacteria (determining species as well as rifampin resistance) and a DNA chip for HIV genotyping. In the long term, these diagnostic reagents are expected to be incorporated into a fully automated system for the diagnosis of infectious diseases. The project also includes plans to extend the range of diagnostic parameters to other markers so that for a given pathological situation (i.e., respiratory infection, genital infection, etc.), a single GeneChip array will be capable of determining the responsible pathogen type (bacteria, virus, yeast, or parasite), both in terms of species and resistance to drug treatments.

REFERENCES
1 Troesch A., Nguyen H., Miyada C.G., Desvarenne S., Gingeras T.R., Kaplan P.M., et al. Mycobacterium Species Identification and TB Rifampin Resistance Testing with High-Density DNA Probe Arrays, J Clin Microbiol, 1999.
2 Lipshutz R.J., Morris D., Chee M., Hubbell E., Kozal M.J., Shah N., et al. Using Oligonucleotide Probe Arrays to Access Genetic Diversity, BioTechniques, 1995; 19:442-447.
3 Fodor S.P.A., Read J.L., Pirrung M.C., Stryer L., Lu A.T., Solas D. Light-directed, Spatially Addressable Parallel Chemical Synthesis, Science 1991; 251:767-773.

TUBERCULOSIS

A Re-Emerging Disease
Tuberculosis is the number one cause of death due to an infectious disease. According to the World Health Organization, it affects two billion people in the world including symptomatic and asymptomatic cases. Every year it causes three million deaths, including 300,000 children under age 15.1

95% of tuberculosis cases occur in developing countries, generally striking young people and adults from ages 15 to 59.2 Asia is the epicenter of the epidemic; of the 8 million cases that are reported each year, 4.5 million occur in India, China, Pakistan, Indonesia and the Philippines alone.

In industrialized countries, tuberculosis is making a comeback after a marked retreat during the last few decades. This may be explained by the combination of two factors: the worsening of socio-economic conditions in certain segments of the population, and HIV infection. Regardless of the country, today the epidemiology of tuberculosis is closely linked to that of AIDS. The weakening of the immune system actually makes tuberculosis more contagious and therefore fosters the spread of the disease. In 1994 it was estimated that 5.6 million people were infected with both HIV and M. tuberculosis.2 Between now and the end of this century, HIV will be responsible for 750,000 new cases of tuberculosis that would not have otherwise occurred.

Multi-Resistance: An Emerging Problem
Resistance to antibiotics is an issue of growing concern in industrialized countries. Several tuberculosis epidemics due to multi-resistant strains have broken out in the United States since the early 1990s, affecting primarily HIV-infected individuals, with mortality of about 70%.2 Similar situations have been reported in Europe, especially in France and Italy. In France, for example, among the 8,521 strains of tuberculosis bacillus reported in 1992, 42 were multi-resistant.

In developing countries, the inadequacy of surveillance networks limits our knowledge of M. tuberculosis resistance to antibiotics. However, available data suggests that the resistant strains are more common than in industrialized countries, especially in Asia. Several investigations conducted in this region of the world have revealed a substantial number of multi-resistant cases of tuberculosis. Moreover, the 1998 WHO report shows that the countries most affected by tuberculosis do not allocate sufficient resources to combat the disease effectively. This results in tuberculosis treatment being inadequately administered, which encourages the emergence of resistant strains.

Treatment
The treatment of tuberculosis is well established and is designed to meet three objectives: healing the patient, reducing his contagiousness, and controlling the emergence of strains that are resistant to multiple antibiotics. The World Health Organization3 recommends two phases of treatment. The first, which lasts two months, combines high doses of four bactericidal antibiotics to quickly kill most of the bacilli. The second phase, which lasts an additional four to six months, involves the administration of lower doses of antibiotics. It aims to eliminate any residual bacilli and to prevent a possible recrudescence. Rifampin and isoniazid, and to a lesser degree pyrazinamide and streptomycin, are the most effective antibiotics against the tuberculosis bacillus. Ethambutol and thiocetazone exhibit bacteriostatic activity and are combined with bactericidal antibiotics when resistance is suspected.

Prevention: Screening and Immunization
The prevention of tuberculosis depends on early screening and immunization with the BCG vaccine. Early screening allows systematic treatment and thereby limits the spread of the infection.4

Immunization with BCG is included in the WHO’s Expanded Program on Immunization. WHO recommends systematic immunization of all infants during their first year of life in countries with a high prevalence of tuberculosis.4

The value of the BCG vaccine is, however, controversial in countries with a lower prevalence of the disease. Uncertainty about the efficacy of the BCG vaccine has lead certain countries, such as the United States, to discontinue use of the vaccine and to concentrate their prevention efforts on screening and the systematic treatment of infected individuals, whether or not those persons are contagious. Other countries continue to use the vaccine because of its proven efficacy in extra-pulmonary forms of tuberculosis. In this case, two strategies are followed: immunization of risk groups, as is practiced in Austria, Germany, and Switzerland, and systematic vaccination of children in a given age group, as is the case in France.5 This second strategy also includes a policy of monitoring the scar left by the BCG vaccine or testing for a post-immunization tuberculin reaction to determine whether revaccination is necessary.

REFERENCES
1 World Health Organization. State of the World’s Vaccines and Immunization. Geneva: 1996.
2 Raviglione, M.C., Snider, D.E., Kochi, A. Global Epidemiology of Tuberculosis: Morbidity and Mortality of a Worldwide Epidemic. JAMA 1995; 273: 220-226.
3 Maher D., Chaulet P., Spinaci S., Harries A. Treatment of Tuberculosis: Guidelines for National Programs. 1997; Geneva: World Health Organization.
4 WHO Statement on BCG Revaccination for the Prevention of Tuberculosis. Bull WHO 1995; 73:805-806. Ref ID: 6854.
5 Levy-Bruhl D., Guérin N. Les stratégies vaccinales par le BCG dans les pays européens. Santé Publique 1995; 3:283-291.

  • resize text resize text

BioMérieux

You are about to enter the bioMérieux US site

The information contained in this site is specific for the US

We have identified that you are based in Canada where bioMérieux has a site

Worldwide directory

Algeria
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Ivory Coast
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Canada
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

USA
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Argentina
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Brazil
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Chile
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Colombia
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Mexico
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

China
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

India
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Indonesia
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Japan
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Korea
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Philippines
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Singapore
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Thaïland
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Austria
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Belgium
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Czech Republic
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Denmark
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Dubai
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Finland
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

France
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Germany
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Greece
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Hungary
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Italy
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Netherland
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Norway
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Poland
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Portugal
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Russia
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Serbia
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Spain
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Sweden
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Turkey
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

United Kingdom
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

Australia
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

New Zealand
North America

bioMérieux, Inc. - Main Building
100 Rodolphe Street
Phone : +1 919 620 2000 or +1 800 682 2666
Fax : +1 800 968 9494

bioMérieux, Inc. - CSC Building
1101 Hamlin Road
Phone : +1 800 682 2666 or +1 919 620 2000
Fax : +1 800 968 9494

bioMérieux INDUSTRY - St. Louis Office
595 Anglum Road
Phone : +1 314 731 8500 or +1 800 634 7656
Fax : +1 314 731 8678

bioMérieux, Inc. Cambridge office
5 Cambridge Center, Suite 0802
MA 02142-1407, USA Cambridge
Phone : +1 617 679 8000
Fax : +1 617 679 8050

bioMérieux, Inc. - Lombard
1105 North Main Street
IL 60148-1360 Lombard
Phone : +1 630 628 6055
Fax : +1 630 628 6315

loading...
Error