The Spread of Antibiotic Resistance Genes From Biogas Digestors.

[NNadir]

At a relatively late age, I've decided to learn more about a subject in which my knowledge is relatively weak, specifically genomic molecular biology. Toward this end, I picked up a monograph that draws on certain similarities between the study of proteomics - about which I know a reasonable amount - and genomics, specifically with respect to the 3 dimensional geometry, specifically, this one: RNA 3D Structure Analysis and Prediction.

In contemplating my ignorance of genomics, predicated on the ridiculous and ignorant idea that somehow it was "simple" I was struck by the remarks of the structural biologist Michael Levitt of Stanford University who wrote a telling set of remarks than (and considerably more sophisticated remariks I will ever be able to aspire to make) in the introduction to the monograph. To wit:

I first encountered ribonucleic acid in October 1968 (see early history of Computational Structural Biology, Levitt 2001). I worked on RNA for a few years and published three out of my five first papers on RNA (Levitt 1969, 1972, 1973) before abandoning the system as being too simple and not nearly as interesting as protein folding. This was my first of several career-level mistakes. In 1976, I also refused to get involved in the analysis of DNA sequences when Bart Barrell brought me the DNA sequence of jX174 bacteriophage (Smith et al. 1977; Levitt 2001). What I find most surprising about these mistakes is that the decisions seemed very easy when I made them and regrets came much more slowly but lasted longer. In 2008,RNA caught my fancy again thanks to a HFSP International collaboration spearheaded by Michael Kiebler (Medical University of Vienna), and I have now come full circle with four of my five most recent papers involving RNA.

(M. Levitt, pg 1, RNA 3D Structure Analysis and Prediction, Westoff and Leontis, Eds, Springer, 2012)

As Dr. Levitt knows on a highly technical level, and as I now now on a far more primitive level, there is nothing simple about the molecular biology - in his case structural molecular biology, in the broader sense functional molecular biology as derived from structure - of genomics.

With an eye to ameliorating some of my ignorance, I have begun to scan and dig a little deeper into some types of papers that I previously skipped over when perusing my favorite scientific journals, such as the paper I will now discuss, this one:

Antibiotic Resistance Genes and Correlations with Microbial Community and Metal Resistance Genes in Full-Scale Biogas Reactors As Revealed by Metagenomic Analysis (Environ. Sci. Technol., 2017, 51 (7), pp 4069–4080)

I am a critic of so called "renewable energy" in general, particularly the solar and wind industries which I regard as expensive failures that have proved difficult to afford and wasters of (most critically) time in a time of very real crisis. This said there is one form of so called "renewable energy" for which I am working to have some sympathy, specifically the use of biomass. The reason is that no matter how hard I think there seems to be no tool quite as well suited to remove carbon dioxide from the atmosphere - something that it is increasingly clear that future generations may need to do under extremely dire circumstances - as biomass, since it is self replicating in such a way as to be capable of providing huge surface areas, a necessary, if not sufficient, condition of gas exchange for dilute gases like carbon dioxide.

A little known fact about why China was open to receiving Richard Nixon in the late 1960's and early 1970's was because they needed a technology in which (at that time) the United States was a world leader, the industrial technology of nitrogen fixation, since there was a very real risk of famine in China owing to the depletion of its soils in the period leading up to, and during, the Cultural Revolution.

Up until that time, China relied on recycling the key materials associated with the real "green" revolution of the 20th century - that of agricultural production - fixed nitrogen and phosphorous. This involved the long and ancient process of spreading the fields with human and animal waste. However this system can never actually be closed, some of the nitrogen and some of the phosphorous is lost as run off, and thus artificial replenishment is critical where ever a large population needs to be supported: This is true of China, but moreover, the world.

Today, China is a world leader in nitrogen fixation technology - the Haber process - but the Haber process is - and there's no facile solution for this - a huge environmental problem, and in any case, phosphorous must be mined or recovered. Thus China, facing the need to displace coal among other things, has a large infrastructure devoted to the historic practice of spreading human and animal wastes on its fields - after recovering some of the energy from these wastes as biogas produced in large digestors.

We're saved.

After digestion, the phosphorous and much of the nitrogen remains behind and these are spread on the fields. But something else remains: genes, specifically the genes of microorganisms.

The intellectual Lilliputians at Greenpeace are unfamiliar with the contents of any science books, and they like to imagine that gene exchange is something they can seek to ban by appeals to fear and ignorance; similar to the appeals to fear and ignorance they direct against nuclear energy.

Bacteria however, don't give a shit what the morons at Greenpeace think, and they go along happily exchanging genes without reference to people assembling at protests wearing monkey suits to trivialize important events, just as they have done for billions of years.

And some of the genes they exchange are antibiotic resistance genes, which represents a huge threat to human health as most of the spectacular increases in human life spans in the 20th century were connected not only to nutrition, but to the rise of antibiotics. However these two issues, antibiotics and nutrition have some negative feedback loops as the Environmental Science and Technology paper just cited makes clear. The difference between human and animal shit in China in 2017 and that in 1967 is the presence of antibiotics in the former.

Some text from the paper:

Anaerobic digestion (AD) has increasingly been used in the treatment of organic wastes and agricultural residues. AD haste advantages of low energy input and generation of renewable energy in the form of biogas. The digested residues are generally reused as fertilizer. In this way, nutrients in the organic wastes are recycled.1 The utilization of digested residues helps to increase crop production and reduce the use of mineral fertilizers.2 Nevertheless, the content of antibiotic resistance genes (ARGs) in the digested residues might increase the spread of antibiotic resistance,3,4 and therefore, the emergence and spreading of ARGs are currently urgent public health issues globally.5

Spreading of ARGs in the environment is a result of the extensive antibiotic use in humans and animals.6 It has been reported that farm antibiotic use is correlated with the rise and spread of ARGs in human bacterial pathogens.7,8 In addition, metals were shown to select for not only metal resistance genes(MRGs) but also ARGs.9,10 Berg et al. demonstrated that Cu exposure coselected for resistance to clinically important antibiotics (e.g., vancomycin).11 ARGs can be spread among different microbial populations via horizontal gene transfer.26Thereby, bacteria with antibiotic resistance can be formed, which could easily infect humans by contact or consumption of raw vegetables.12 Mobile genetic elements, including plasmids, integrons, and insertion sequences, are crucial for horizontal gene transfer of ARGs in the environment.13,14 ARGs were speculated to be uncorrelated with microbial communities due to high mobility caused by horizontal gene transfer.15,16

Two of the authors are from the PRC, one is from Hong Kong, and one is from that offshore oil and gas drilling hellhole, Denmark, which is a world leader in so called "renewable energy," but is still, nonetheless, an offshore oil and gas drilling hellhole.

The Danes have lots of biodigestors. They're very "renewable conscious" in Denmark and collect biogas even as they drill for what is called "natural" gas in the Baltic Sea.

From the text:

In Denmark, there are more than 40 centralized biogas plants, and they are running with manure and industrial wastes as feedstock.27,28 Moreover, most of the WWTPs have full-scale biogas reactors treating the primary and secondary sludge. It is necessary to understand the presence of ARGs in the digested residues from full-scale biogas reactors to properly define the risks posed by land application. The present study made detailed comparative analysis of ARGs in various full-scale biogas reactors via the HTS-based metagenomic approach to provide a new insight of ARG profiles in biogas reactors. The objectives of the study were: (1) to reveal the diversity and abundance of ARGs; (2) to identify the key environmental variables determining the ARG contents; (3) to investigate the correlation between ARGs and microbial communities; (4) to understand the co-occurrence of ARGs and MRGs in various full-scale biogas reactors.

(WWTP is an abbreviation for "Wastewater Treatment Plants" and HTS, depending on context can mean either "High Throughput Sequencing" or "High Throughput Screening." MRG are "metal resistance genes&quot

If you're as interested in learning about the technology of genetic analysis as I am, this paper is a fun and interesting read, although I won't claim to understand how everything described in it works.

What's important is the conclusion, the spreading of biodigester residues on crops and fields has a very real risk of spreading antibiotic resistance, particularly because of the facilities with which bacteria exchange genes. (There are nice graphics in the paper that draw this out.)

By the way, my own belief is that there are brute force approaches to capturing and utilizing the carbon contained in biomass that are superior to digestors, which are cute, and all "renewally" and therefore fashionable.

This is high temperature thermal reforming.

But that's another issue.

The paper is interesting, a little bit fun, but also a little bit scary, given all the other huge problems we've dumped on the up and coming and all future generations. We'll just add the destruction of the efficacy of antibiotics to the list, along with climate change, mass extinction of biodiversity, material depletion...on and on and on...

Have a nice Sunday.

[Warpy]

1. Well, back when I was in nursing school

we were all taught about bridging between bacteria to exchange useful genetic adaptations. Antibiotic resistance is one of the most useful ones for pathogens and now research has confirmed even non pathogens are passing it around. The inescapable conclusion is that antibiotic resistance will continue to grow and that the antibiotic age in which every 2 year old with an earache or factory farmed meat animal gets treated with antibiotics is just about over. The genie is out of the bottle and there is no way to stuff him back in because he's too big and there is no way we can get a grip on him.

Given another century, very few bugs out there will be susceptible to penicillins. Spreading resistant bugs on fields with sludge is not going to add much to the problem that is already getting out of control.

Yes, other strategies are being explored, like whatever it is that keeps the Komodo dragon alive when pathogens have killed all its closest relatives, but that's years away. In the short term, it might be harvesting antibodies from people who survived disease, rather like they were starting to do before penicillin came out.

Then again, pneumonia was always called "the old man's friend," so there might be an upside to antibiotic resistance across the whole bacterial spectrum.

[KT2000]

2. There are people working

on this issue. A friend is leading efforts in Washington to stop the spread of sewage sludge for the very reasons you have noted.
She says high heat incinerators are what is needed.
Here is a page that has some fact sheets and info about what people are doing to stop the contamination caused by sewage sludge. In addition to being spread on crops, it is being sprayed in our state forests.

https://sierraclub.org/washington/north-olympic/sewage-sludge-free-washington

[NNadir]

3. You are correct, lots of people are working on this. Each week I encounter...

...new papers on the topic of approaches to the problem in the Engineering and Scientific Journals I read.

These papers fall into several classes, discussion of the risks associated with current practice - which is the class into which the paper cited in the OP is - papers devoted to new processes and their potential risks, and papers about potential products that might be obtained from sewage processing.

Your friend is right, heat of course, in general, ameliorates that problem, but it does not address other problems associated with the processing of sewage sludge, for example heavy metals (which was actually part of the subtext of the paper cited in the OP):

Distribution Characteristics of Heavy Metals in Different Size Fly Ash from a Sewage Sludge Circulating Fluidized Bed Incinerator

or sulfur:

Sulfur release and migration characteristic of sewage sludge combustion under the effect of organic calcium compound addition

or nitrogen:

Interaction Characteristics of Mineral Matter and Nitrogen during Sewage Sludge Pyrolysis

I selected these papers more or less at random from a search of the five major scientific journals I always at least scan and often read over the last seven years, a list that gets 100 hits (on the ACS website). A search on Google Scholar containing the term "sewage sludge" gives more than 48,000 hits since 2010.

I agree with the editorial remarks in this paper:

We Should Expect More out of Our Sewage Sludge

My environmental philosophy consists of the view that there should be no such thing as "waste," that all products of our human activities should either be useful or non-existent. My view is that if we cannot find a use for what is (currently) considered "waste," we should not generate it, or at least not generate any that cannot be combinatorially optimized to most manageable with the least amount of risk. (Scientists understand risk fairly well, even if the general public and the politicians the general public allows to rule them are completely clueless on the subject.)

Sewage sludge can be an important resource, and the resource which most concerns me, beyond the carbon sources in it is phosphorous:

Some constiuents of sewage sludge, for example, phosphorous are issues that we fail to address at our peril. Our food supply depends wholly on the phosphorous cycle. And people are thinking on a very deep level about this.

Molecular Design of Nanofiltration Membranes for the Recovery of Phosphorus from Sewage Sludge

As is the case with many major environmental problems, there is a huge divide between the upper 10% in terms of wealth, and the poorest 90%. In the case of the poorest of the poor, let's say the 3.5 billion people in the lowest half in terms of wealth, often the problem is that there is nothing for them available for the treatment of human and animal waste.

I frequently cite in this space, in another context, the Lancet paper evaluating the risks associated with various human practices and conditions, this one:

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 (Lancet 2012, 380, 2224–60

According to this paper, the death toll from the lack of any sanitation was responsible for close to 350,000 deaths in 2010, happily down from 700,000 deaths in 1990.

As we are seeing in China, and to some extent in India, addressing the problems of the third world generates a new set of first world consequences.

We must always think deeply about the consequences of our economy, and recognize that both in moral and intellectual spheres, there are no perfect solutions, but only optimal solutions. Perfect and optimal are very different things.

The real issue is the fight against ignorance. Unfortunately, after many years of progress against ignorance, it is now actually rising all around the world as we can see in a plethora of news sources. (Here in the United States, as we all discuss on this site, we have the most ignorant government we've had in more than a century.) But the embrace of ignorance is not merely a reflection of one's position on the political spectrum, by the way. One can see impossibly ignorant statements being made on the left that are just as pernicious as those on the right, something with which I have some personal experience. Even the Sierra Club can engage in rhetoric that is environmentally ignorant, although that is not the case with the fine link you supply.

Thank you for your comment.

[defacto7]

4. I want to thank you for your op and others

for their responses. I don’t find too many inspiring sources that challenge my perspectives or lack of them. There are many potent ideas packed in these links and comments; my interest is perked. Maybe I just haven't been listening but it's great to have a new study... I love that... new questions, updsted opinions, and hopefully better understanding.