Shotgun metagenomics: Not just a pretty face (commentary)

Research looks to better define the relationship between the environment and food when it comes to antibiotic-resistant bacteria.

I don’t usually venture into areas that I am not very familiar with for my food safety blogs because then I probably would not be able to answer the questions that might follow, but today I am making an exception.

What I am about to pen is just that game changing, that important and that exciting even if I don’t understand how it works.

A couple of digital news outlets, including Feedstuffs, recently told stories about some exciting work being done just down the street from me at Colorado State University, and cited a most recent research article published in eLife entitled “Resistome diversity in cattle and the environment decreases during beef production.”

Even my spell check does not recognize resistome. That makes me feel a little bit better.

The paper can be accessed at http://dx.doi.org/10.7554/eLife.13195.

I was interested enough that I read the actual paper, or better said, I tried to read it.

It is way more detailed, scientific and over this old country doc’s head to be able to discuss it over a cup of coffee.

So I called an old friend, Dr. Keith Belk, co-principal investigator for the National Cattlemen’s Beef Assn. (NCBA) funded research project, and current Monfort Endowed Chair for the Center for Meat Safety and Quality, Department of Animal Sciences, Colorado State University (CSU).

Belk was kind enough to give me an hour of his time and expertise along with that of the lead author, Dr. Noelle Noyes.

It turns out that this is just one report out of 12 eventual studies and reports (two are already published) that CSU is working on thanks to nearly $3 million in grants from the U.S. Department of Agriculture, the Beef Checkoff and other private sources.

One NCBA grant will take a closer look at the use of macrolides to prevent liver abscesses in cattle in feedlots. More on that one in a later blog, as it is a particular concern to me that we not jeopardize the effectiveness of a macrolide (the Z-Pack) used in human health as the antibiotic of choice for community acquired bronchitis and sinusitis, along with several other ailments.

The study I was interested in for today’s discussion sampled environmental samples from eight pens in four feedlots located in Texas and Northern Colorado, looking for antimicrobial resistant determinants by looking at all resistance genes within all the bacteria in each sample.

It also took samples from the trucks moving the cattle to abattoirs, the holding pens at the abattoirs and then sampled the final beef products.

It turns out that the possibility of a human being adversely affected by antibiotic resistant bacteria associated with the beef production might carry a greater risk from the environment than from the consumption of the meat.

Another interesting finding was that the microbiome between pens was very similar and that the environmental samples from the Colorado and Texas feedlots, located hundreds of miles apart, were also very similar.

This finding is regardless of what antibiotics were used and for how long, although all feedlots used similar antibiotics, including in-feed tylosin.

We knew that if you sampled members of a household, including the pets, their microbiome will be more similar compared to other households, but we had never done that for pen pals (please excuse the attempt at humor).

Instead of looking at pathogens, one by one, the new shotgun metagenomics approach studies hundreds or thousands of bacterial species in a sample, instead of just a few based on DNA.

Using this DNA from all of the bacteria in a sample, the researchers were able to look for over 4,000 known resistance genes using next generation sequencing. It is all about affordability and advances in science and technology.

Belk pointed out that this new testing is so easy and now affordable as comparable to the advances from the first IBM computers that were bulky and needed temperature controls. It is now available on smart phones that everyone uses to check the weather forecast and the stock market three times a day.

As another example of the change that has taken place, the effort to sequence the first human genome took 13 years, $3 billion and the human genome is 3 billion base pairs of DNA.

The first sample CSU examined took seven days to sequence, cost $900 and got 8 billion pairs of DNA.

Game changing technology, but where will it take us?

Hopefully to antibiotic use policies based on this type of new science capacity, not policy based on political science as too often happens.

This information is critical to understanding the ecology of antibiotic resistance, including the horizontal transfers of resistance genes and the jumping of plasmids from one species of bacteria to the next.

As just one example of this need, the researchers found carbapenem-resistant bacteria in the feedlots. Carbapenem is not allowed for use in animals raised for food.

How did it get there? My CSU friends could only say, “this will come with a very steep learning curve.”

Looking at DNA for resistomes will change how we think, just the same as looking at DNA in pathogenic bacteria using PFGE changed the game in identifying and controlling foodborne illness outbreaks.

Exciting stuff, even if I can’t talk the talk.

I do think one way to dummy this whole effort down is to say that the researchers are trying to better define the relationship between the environment and food when it comes to any risk to our health as it relates to antibiotic-resistant bacteria.  

But this is not a one man, one woman, effort.

 It is not even a one department effort, nor is it a one school effort.

To do what they just did took a very large, and a very diverse group of individuals and institutions.

I am sure I may leave out a couple, but led by the CSU department of animal sciences and clinical sciences, other contributors to this work and ongoing work include the University of Colorado’s Anschutz Medical Campus,  CSU’s computer sciences and microbiology, immunology and pathology departments, the Public Health Agency of Canada and Agri-Food Canada Lethbridge Research Station, and the USDA’s Meat & Animal Research Center in Clay Center, Neb.

It can be tough to talk about something that is hard to understand as a lay person.

One of the news articles said that CSU tested “meat and fertilizer samples”.

I guess if you consider collecting fecal and soil samples in the pens of a feedlot “fertilizer”, that statement might be correct.  

Noyes just thought that a pretty liberal interpretation of the science behind the study.

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