Clinical OMICS

JAN-FEB 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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22 Clinical OMICs January/February 2017 www.clinicalomics.com is having on the study of resistance is "the ability for us to transcend the culturing barrier. So much of micro- biology and the functions encoded in microbiology, such as resistance, are based on ideas of domesticating microbes by bringing them into the lab and studying them deeply. While this method has been very useful, we've learned from soil and environmen- tal researchers, as well as the human microbiome project and beyond, that most habitats have rich microbial communities that are not trivial to cul- ture. So genomics sort of gets beyond that by going after the nucleic acids themselves and inferring what the functions might be—and the study of resistance has been expanded because of that approach." The influence of genomics on fields like microbial genetics is best viewed through the lens of advanced techniques such as next-generation sequencing (NGS), which has quickly evolved into an affordable method now employed in both research and clinical settings. For microbiologists tasked with monitoring mutations within microbial populations that could lead to resistance, being able to quickly and accurately assess bacterial genotypes is paramount in attemping to stay ahead of drug resistance outbreaks. Whole-Genome Sequencing (WGS) Gains Appeal "WGS of bacteria has become a fast and affordable technology that is being adopted by federal agen- cies (including the FDA, CDC, and USDA) and state health laboratories, and will soon become an integral part of laboratory science world- wide," explains Patrick McDermott, Ph.D., director of the U.S National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria at the U.S. Food & Drug Administra- tion (FDA). "By providing definitive genotype information, WGS offers the highest practical resolution for detecting and characterizing the full complement of resistance determi- nants, whether acquired exogenously or arising by mutation, including resistance to antibiotics not routinely tested. Sequencing different bacte- rial species isolated from different sources (humans, animals, foods, and The ability to work outside of the typical microbiological paradigm for adapting bacteria to laboratory culturing systems always has excited researchers about meta- genomics—which analyzes micro - bial DNA directly from environmental communities. "It allows us to identify the array of resistance genes in a complex matrix without the need to culture organisms in the lab on artificial growth media," explains Patrick McDermott, Ph.D., direc- tor of the U.S. National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria at the FDA. "For the purposes of NARMS, this represents a tremendous advancement. By indexing what we find, to the resistance in human pathogens, we essentially will be con- ducting reconnaissance of the environ- mental microbiome and assessing its evolving risks based on changing resi- stome patterns in the clinical setting." While previous work in metagenomics had been done to not only show that the concept was feasible, scientists conse- quently discovered that gene diversity in the microbial world varied tremendously. However, traditional sequencing tech- niques made the genomic analysis pro- cess difficult and labor intensive. It wasn't until next-generation sequencing tech- niques became more mainstream and cost-effective that investigators began to give metagenomics a second look. "Metagenomics really was a game changer, as it allowed us to look at resis- tance genes in various habitats," stateds- Gautam Dantas, Ph.D., associate professor in the department of molecular microbi- ology at Washington University School of Medicine "What's clinically relevant about this, is that it's been pretty well estab- lished that the evolutionary antecedents of resistance are in the soil—and almost certainly that next new resistance gene discovered in the clinic will come from these environmental microbes." Additionally, it's a strong bet that if new resistance genes are found in the soil, so too are ways to combat them. The future will see metagenomic applica- tions leading the way on the resistance surveillance and drug discovery fronts. " The impact of genomics is that it allows us to see a much larger part of the pie," Dr. Dantas added. "What I would claim with functional metagenomics, it's not that we just expanded how much of the pie we could now describe, we real- ized that the pie was substantially larger than we initially imagined." n (continued from previous page) (continued on page 24) Neutrophil, a human white blood cell (blue) interacts with rod-shaped, multidrug- resistant Klebsiella pneumoniae bacteria (pink) in this digitally-colorized scanning electron microscopic image. David Dorward; Ph.D. / NIAID The Future Is So Meta

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