Phenotype MicroArray technology making breakthrough discoveries on tuberculosis bacterium

In a paper recently published in the journal PLOS ONE, a research team headed by Dr Paul Wheeler from the UK Animal Health and Veterinary Laboratories Agency (AHVLA) reported breakthrough progress in understanding the metabolic and phenotypic properties of the bacterium Mycobacterium tuberculosis and its close relative Mycobacterium bovis. Mycobacterium tuberculosis is the causative agent of the transmissible respiratory disease tuberculosis, which infects an estimated 8 million people worldwide and is responsible for 2 million fatalities each year. Mycobacterium bovis afflicts cattle, with losses to agriculture of approximately $3 billion per year. These mycobacteria have been very difficult for scientists to study because they grow very slowly, so experiments can take weeks or months to perform.

The publication from the AHVLA shows that Biolog’s Phenotype MicroArray (PM) technology allows the bacteria to be studied much more quickly and easily, which will accelerate the pace of mycobacterial research. Results can be obtained in seven to 10 days. The paper further demonstrates diagnostic potential by phenotypically differentiating strains of these mycobacteria with different host ranges and levels of pathogenicity. The paper also expands, as well as confirms, our knowledge of the metabolic properties of the mycobacteria. As a consequence, genome annotation can be improved, the biology of these bacteria can be better understood and hopefully these insights will facilitate discovery of antibiotics more effective in their eradication.

According to Dr Wheeler, “The genome sequence of Mycobacterium tuberculosis was published in 1998 and high-throughput phenotype analysis of pathogenic mycobacterial strains is urgently needed and long overdue. Molecular typing of Mycobacterium strains has limitations. Though key in surveillance and helpful in identifying emerging strains, it does not provide information on biological properties or phenotypes. This is a substantial gap in our knowledge since it is the phenotype which is selectable and must relate to the evolutionary advantage of one strain over another.”

Other mycobacterial species have also been successfully studied with PM technology. In June 2012, researchers in the laboratory of Professor Yung-Fu Chang at Cornell University College of Veterinary Medicine published also in PLOS ONE on their use of PM technology to analyse the metabolic phenotypes of Mycobacterium avium. In 2009, a team of researchers in the laboratory of Professor Lacy Daniels at Texas A&M used gene knockouts combined with PM technology to show that the Mycobacterium smegmatis gene homolog of the Mycobacterium tuberculosis gene Rv1238 codes for a transporter of the sugar trehalose and plays a critical role in pathogenicity. Additionally, in a paper published in January 2013 in the Journal of Bacteriology, Professor Daniels’ lab again analyses the phenotypes of gene knockouts with PM technology to define the spectrum of antibiotics and antiseptics for mycobacterial efflux pumps. Antibiotic resistance is another focus of mycobacteria research.

“We are thrilled that three laboratories have now successfully applied Biolog’s PM technology in pioneering research resulting in breakthrough discoveries,” said Dr Barry Bochner, CEO and CSO at Biolog. “PM technology is designed to provide high-throughput phenotyping and metabolic scanning of cells, making it a powerful complement to genotyping experiments.”

Phenotype MicroArray technology, initially developed with SBIR funding from NIH, is thus proving to be a cell profiling technology that can yield breakthrough discoveries. It allows scientists to study the growth properties and culture condition responses of bacterial, fungal and even human cells. As such, it is becoming a core technology for many cellular studies.