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And the third thing : Spend the time to optimize your workflow for the best DNA extractions and results in your laboratory . When you get a brand new machine , you may have really good experiments already planned . But , as exciting as that is , you should start with a reference strain where the sequences have already been determined , and figure out how to get the highest quality data out of your system . Spend the time to optimize your DNA extractions and the quality of the libraries you ’ re generating .

What have been some of your most exciting or most unexpected research findings ?

I worked on botulism for several years and one of our projects was to better understand the diversity of botulinum toxin genes to inform the development of strain panels for evaluating new detection assays such as PCR and ELISA . In sequencing these strains we identified some with a unique toxin gene , and the variation was in the part of the gene that encodes the enzymatic part of the toxin — the part that actually cleaves host synaptic proteins . Based on these differences , we predicted there might be a new or different function for these toxins . Another group of CDC researchers was able to test this hypothesis using mass spectrometry to measure where the newly characterized toxins cleave proteins . It turns out they cleave them in a whole new place . This finding actually impacts some diagnostic assays for botulism . This stands out to me as an example of the power of DNA sequencing to learn about new gene functions . It ’ s pretty awesome to be able to predict real changes in function that might even affect disease .

Legionella , the bacterium responsible for Legionnaire ’ s disease , has caused outbreaks of late , everywhere from Sydney , Australia , to Flint , Michigan . What is driving the rise in cases ?

Cases have been increasing for more than a decade in the US and some other parts of the world . It ’ s not entirely clear what ’ s driving the increase ; probably multiple things , such as increases in diagnostic testing , increases in susceptible populations ( with risk factors like advanced age , underlying lung disease or weakened immune system ) and potentially increases in environmental sources . Legionella is found in manmade water systems and under the right conditions , the bacteria can grow and become aerosolized .

What has NGS revealed about Legionella and how will this new knowledge impact public health interventions ?

We are discovering that Legionella is incredibly diverse , and we are recognizing that some strains may be more common in certain geographical regions . One of our goals at CDC is to apply NGS methods to improve environmental source attribution . Faster methods to pinpoint the source of an outbreak can potentially prevent more cases of illness . We are also beginning to study the ecology of the organism within the complex microbial communities of the built environment , which may inform Legionnaires ’ disease prevention activities .

Do you expect the incidence of Legionnaire ’ s disease to tick upward during the summer months ? Can we ever expect to eliminate this microbe ?

There is a typical seasonal increase in Legionnaires ’ disease cases in the summer , which is often when some of the larger outbreaks occur . Warmer

temperatures support growth of the organism in the environment .

Because Legionella occurs in natural water systems — ponds , lakes and rivers — it ’ s unlikely we ’ ll eliminate the organism from the natural environment . What we can do is prevent it from multiplying to large numbers in manmade water systems . CDC just published a toolkit to help building owners reduce the risk of Legionella in their facilities [ posted at www . cdc . gov / legionella / WMPtoolkit ].

What are some of your current , and possible future , collaborations with state public health laboratories ?

We recently published a joint article with the New York State Department of Health looking at genomes of Legionella strains collected in New York and the utility of different methods to compare these sequences . A major aim of the Advanced Molecular Detection Legionella project is to pilot test a whole genome multi-locus sequence typing ( wgMLST ) scheme for this organism with various state and local laboratories . This standardized approach will enable reproducible results from WGS across laboratories .

Imagine it ’ s 2025 . What do you see as the state of PHL practice with regard to NGS ?

I think NGS will be as common in 2025 as PCR is now . Sequencing is becoming a first line test in microbiology — but it is not necessarily the end of the line . I think there still is a place for culture in the microbiology laboratory in 2025 . We can ’ t discount the emergence of new microbes and strains that we will need to understand in more detail , and for this , they ’ ll have to be isolated using culture .

Bioinformatics is going to be key as we sequence complex samples using metagenomic techniques . Bioinformaticians will partner with microbiologists and epidemiologists to answer challenging questions in public health . Many of these projects have already begun but the tools to do this kind of work routinely are still being worked out .

What is the most amazing thing you ’ ve learned about microbes ?

I think people tend to underestimate microbes . They are incredibly diverse and strains with novel characteristics can emerge quickly so we can ’ t become complacent . New technologies are giving us amazing opportunities to learn more about these microbes faster than ever before and public health laboratories are often where novel strains are discovered .