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Curetis Subsidiary to Leverage Bacterial Genomic Database for Antibiotic Resistance Testing

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NEW YORK (GenomeWeb) – German molecular diagnostics firm Curetis has launched a subsidiary that it expects will contribute to its core infectious disease diagnostics business, while moving the firm into new applications and expanding opportunities for collaboration.

The new subsidiary, called Ares Genetics and based in Vienna, Austria, will leverage a bacterial genomic database to identify antibiotic resistance markers and develop informatics for interpretation and treatment guidance. It also has plans to license the database to pharmaceutical companies for drug development purposes.

Curetis decided to form Ares Genetics after acquiring the Genetic Antibiotic Resistance and Susceptibility Database (GEAR) from Siemens when Siemens sold its microbiology business to Beckman Coulter in 2014. The database contains genomic sequence data of more than 11,000 bacteria, as well as resistance information from those strains on 21 different antibiotics.

The company was interested in leveraging the database for its existing business. It already screens for some antibiotic-resistance markers using its PCR-based Unyvero platform, and thought the GEAR database could be crucial in identifying novel biomarkers to include in its assays. But, the firm also identified other potential business opportunities, including using the database for research purposes to study resistance mechanisms, in drug development, and to develop treatment decision-making reports.

"That led to the idea that there is a whole different and more extensive business model around GEAR that has its own risk-benefit profile, which led to the conclusion that we'd rather pursue that in a subsidiary," said Achim Plum, chief commercial officer of Curetis who will also serve as managing director of Ares.

Curetis also tapped the expertise of Andreas Posch, who had joined Curetis in March from Siemens. Posch was head of bioinformatics at Siemens and responsible for GEAR. Plum and Posch are now putting together a small core team at Ares.

Plum said that in the near term, Ares would focus on using the data in GEAR to identify and validate antibiotic resistance markers that Curetis could incorporate in its molecular diagnostic tests. Its Unyvero platform, which is based on PCR technology, already includes a few antibiotic resistance markers, Plum said, but the firm plans to add to those.

Although the data within GEAR was all generated using next-generation sequencing technology, Plum said that in the near term, Curetis did not have plans to migrate its PCR tests to NGS. Plum anticipated that biomarkers identified from the database could start to be incorporated in Curetis' tests in the two- to three-year time frame.

Also in the near- to mid-term, Ares plans to make the database available as a research platform for the academic and clinical research communities in some sort of public-private partnership, Plum said, enabling researchers to use the database to study resistance mechanisms.

One such partnership will be with Andreas Keller, who heads the clinical bioinformatics group at Saarland University. Keller's group collaborated with Siemens to develop the GEAR database and will continue to work with Curetis to further develop it, Plum said.  

Another mid-term goal will be to forge R&D and licensing agreements with pharmaceutical companies that could use the GEAR database to develop better drugs, Plum said. Once the "mechanisms of action are described in the GEAR database and it's known what's responsible for resistance in microorganisms, that's a good starting point for pharmaceutical research to develop more effective drugs," he said.

Longer term, the company plans to develop interpretation tools based off of GEAR, Posch said, such that a clinical specimen can be sequenced, compared to the database, and a resistance profile can be quickly determined.

Additional development will be needed to develop such tools, Posch said. For instance, "the database was developed from bacterial isolates, so there is still some development necessary to make it applicable to true clinical specimens," he said. For instance, metagenomic NGS sequencing is a rapidly growing field, so the database would ideally be able to handle such samples, which includes not only genomic data from the causative pathogen, but also genomic data from the non-pathogenic bacteria the patient harbors, he said.

In this type of application, Ares would serve as the bioinformatics company that develops the functionality for a diagnostic company developing an NGS-based test, Plum said.

"The development of such a product is doable within a reasonable timeframe," Plum said, "but adoption of such a product will depend in part on the market for using NGS as the routine frontline technology in infectious disease testing, which is probably still a couple years away."

Plum anticipated that even as the market for NGS-based infectious disease testing grows, it will not replace PCR-based testing soon. The technologies will coexist, he said, with NGS-based testing initially used for problematic and difficult to diagnose cases. And, although Plum said that Curetis did not have plans to shift to NGS-based testing, as the market moves in that direction the interpretation products offered by Ares would serve as a strategic footprint in the space.

As the market for NGS-based infectious disease testing grows, databases like GEAR could play an important role in rapidly identifying a causative pathogen complete with a resistance profile from genomic data. But it is not the only database being developed for such purposes.

One such database is the Comprehensive Antibiotic Resistance Database (CARD), developed by researchers at McMaster University in Canada. The CARD database includes curated reference sequences, and as of August 2016 it included 2,441 model reference sequences, as well as more than 850 SNPs associated with resistance. It also contained 2,260 resistance detection models, most of which were protein homolog models.

The National Center for Biotechnology Information also has a pathogen detection project in which it is focusing on sequencing four bacterial groups that are the main causes of foodborne illness. Meanwhile, other bioinformatics pipelines are pathogen-specific, for instance TBProfiler, developed for tuberculosis.

In Europe, the publicly funded European Antimicrobial Resistance Surveillance Network has been collecting antimicrobial resistance data, and a University of Oxford team is working on developing a tool called Mykrobe Predictor to identify species and resistance profiles of bacterial strains.

Posch said that Ares aims to set itself apart primarily by the sheer scope of the GEAR database, which includes not only whole-genome sequencing data for more than 11,000 pathogens, but also "comprehensive phenotypic data on antibiotic susceptibility." As such, GEAR "already today allows us to monitor the emergence and spreading of antibiotic-resistant pathogens over the past three decades and contains data on numerous novel genetic mechanism of resistance," he added. 

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