Progress in the development of vaccines against rumen methanogens

Wedlock, D. Neil; Janssen, Peter H.; Leahy, Sinead C.; Shu, Dairu; Buddle, Bryce M.

doi:10.1017/s1751731113000682

Cited by 50 publications

(36 citation statements)

References 49 publications

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“…Understanding these differences has been the scientific motivation to pursue the development of selective inhibitors of methanogenesis that are nontoxic to animals (17,18). Only recently, a compound has been described that apparently can both substantially decrease CH 4 and increase propionate productions in the rumen without compromising animal performance and health (19).…”

Section: Significancementioning

confidence: 99%

Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol

Duin

Wagner

Shima

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

178

167

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Ruminants, such as cows, sheep, and goats, predominantly ferment in their rumen plant material to acetate, propionate, butyrate, CO2, and methane. Whereas the short fatty acids are absorbed and metabolized by the animals, the greenhouse gas methane escapes via eructation and breathing of the animals into the atmosphere. Along with the methane, up to 12% of the gross energy content of the feedstock is lost. Therefore, our recent report has raised interest in 3-nitrooxypropanol (3-NOP), which when added to the feed of ruminants in milligram amounts persistently reduces enteric methane emissions from livestock without apparent negative side effects [Hristov AN, et al. (2015) Proc Natl Acad Sci USA 112(34):10663–10668]. We now show with the aid of in silico, in vitro, and in vivo experiments that 3-NOP specifically targets methyl-coenzyme M reductase (MCR). The nickel enzyme, which is only active when its Ni ion is in the +1 oxidation state, catalyzes the methane-forming step in the rumen fermentation. Molecular docking suggested that 3-NOP preferably binds into the active site of MCR in a pose that places its reducible nitrate group in electron transfer distance to Ni(I). With purified MCR, we found that 3-NOP indeed inactivates MCR at micromolar concentrations by oxidation of its active site Ni(I). Concomitantly, the nitrate ester is reduced to nitrite, which also inactivates MCR at micromolar concentrations by oxidation of Ni(I). Using pure cultures, 3-NOP is demonstrated to inhibit growth of methanogenic archaea at concentrations that do not affect the growth of nonmethanogenic bacteria in the rumen.

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Section: Significancementioning

confidence: 99%

Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol

Duin

Wagner

Shima

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

178

167

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“…Modern vaccine development has seen a change towards genome-based 'Reverse Vaccinology' approaches that use high-throughput in silico screening of an organism to identify genes that encode proteins with the attributes of a good vaccine target (Dormitzer et al, 2012). This approach to identify targets for a methanogen vaccine has already proven fruitful, as sequence-based bioinformatic analysis of M. ruminantium M1 has led to the identification of a large number of potential vaccine targets for evaluation and, to date, two lead candidates Wedlock et al, 2013). The increasing number and diversity of rumen methanogen genomes available for comparative and pan-genomic studies will make this approach more powerful and will greatly assist in the search for cross-reactive and efficacious vaccine antigens.…”

Section: Vaccinesmentioning

confidence: 99%

“…Vaccines based on whole methanogen cells have had limited success at reducing CH 4 emissions in sheep (Wright et al, 2004), which may be because of a failure of this type of vaccine to produce cross-reactive antibodies. A recent strategy for vaccine development is based on identifying relevant methanogen protein antigens, which can be used for a sub-unit vaccine (Wedlock et al, 2013). Such antigens need to be accessible for antibody binding, and thus vaccine candidates could include membrane associated/surface exposed proteins and adhesin-like proteins.…”

mentioning

confidence: 99%

“…Such antigens need to be accessible for antibody binding, and thus vaccine candidates could include membrane associated/surface exposed proteins and adhesin-like proteins. The two main approaches to identifying such vaccine candidates have been the identification of strongly immunogenic proteins using Western blot analysis with sheep antisera raised against various methanogen fractions and the prediction of suitable vaccine antigens through bioinformatic analysis of methanogen genomes (Wedlock et al, 2013). Although the former approach has identified a number of immunogenic proteins, few of these have had the attributes of a good vaccine candidate.…”

mentioning

confidence: 99%

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Genome sequencing of rumen bacteria and archaea and its application to methane mitigation strategies

Leahy

Kelly

Ronimus

et al. 2013

Animal

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Ruminant-derived methane (CH 4 ), a potent greenhouse gas, is a consequence of microbial fermentation in the digestive tract of livestock. Development of mitigation strategies to reduce CH 4 emissions from farmed animals is currently the subject of both scientific and environmental interest. Methanogens are the sole producers of ruminant CH 4 , and therefore CH 4 abatement strategies can either target the methanogens themselves or target the other members of the rumen microbial community that produce substrates necessary for methanogenesis. Understanding the relationship that methanogens have with other rumen microbes is crucial when considering CH 4 mitigation strategies for ruminant livestock. Genome sequencing of rumen microbes is an important tool to improve our knowledge of the processes that underpin those relationships. Currently, several rumen bacterial and archaeal genome projects are either complete or underway. Genome sequencing is providing information directly applicable to CH 4 mitigation strategies based on vaccine and small molecule inhibitor approaches. In addition, genome sequencing is contributing information relevant to other CH 4 mitigation strategies. These include the selection and breeding of low CH 4 -emitting animals through the interpretation of large-scale DNA and RNA sequencing studies and the modification of other microbial groups within the rumen, thereby changing the dynamics of microbial fermentation.Keywords: genome sequencing, methane mitigation, methanogens, rumen bacteria Implications Development of CH 4 mitigation strategies for ruminants without disrupting normal digestive function and reducing productivity is a major challenge. Genome sequencing is an effective way of gaining information on how rumen methanogens and bacteria interact and contribute to rumen function. This knowledge will be important when considering the design and implementation of ruminant CH 4 abatement strategies. Genomic information is already contributing to vaccine and small molecule inhibitor programmes that are aimed at reducing ruminant CH 4 emissions, but it will also underpin the analysis and comprehension of metagenomic sequence data sets, allowing the generation of testable hypotheses to gain a better understanding of rumen biology. IntroductionRuminants are foregut fermenters and have evolved an efficient digestive system in which microbes ferment plant fibre and provide fermentation end-products and other nutrients for growth of the animal (Clauss et al., 2010). Feed ingested by ruminants is fermented by a complex microbial community, which includes bacteria, ciliate protozoa, anaerobic fungi, archaea and viruses. The rumen is the first and largest foregut compartment and is the main site for microbial fermentation. The microbial ecology of the rumen has been the focus of numerous studies (reviewed by McSweeney and Mackie, 2012), but very little information is available regarding the microflora of the ruminant oral cavity and lower gastrointestinal tract. The rumen provides optimal conditio...

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“…Researchers in New Zealand and Australia have also been working on stimulating the ruminants' own immune system to produce antibodies that can suppress the activity of methanogens. Success has been reported in vitro (Wedlock et al 2013) but not so far in vivo. The mode of delivery, the promise of infrequent treatment and the potential applicability to all classes of livestock make this mitigation route highly attractive.…”

Section: Modifying Rumen Processesmentioning

confidence: 99%

The Estimation and Mitigation of Agricultural Greenhouse Gas Emissions from Livestock

Clark

2017

Proceedings of International Seminar on Livestock Production and Veterinary Technology

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Emissions of methane (CH4) and nitrous oxide (N2O) from agricultural activities currently comprise 10-12% of the world's total anthropogenic greenhouse gas (GHG) emissions. They are also forecast to rise by 30% above current levels by 2050. At the Conference of the United Nations Framework Convention on Climate Change (UNFCCC) held in Paris in December 2015, more than 100 countries indicated that they would reduce agricultural GHG emissions as part of the global effort to keep warming to a maximum of 2°C. Emissions from ruminant livestock present a particular challenge as enteric CH4 emissions alone comprise ~40% of total agricultural emissions. Estimating emissions from animal agriculture can be done through simple estimates, generically available data on animal populations and regional-level fixed emission factors per animal. But these estimates are subject to very large uncertainties and their appropriateness for estimating emissions at the country level is questionable. More appropriate country-specific methods can be developed using local data and expert opinion in the first instance, even in the absence of countryspecific emission factors. Reducing GHG emissions from ruminant livestock is challenging technically even if livestock production is constant, and is particularly challenging if the sector is increasing in size. Internationally the quantity of GHG produced per unit of product has been declining consistently and for both cattle meat and milk than 50 years ago. This decline is largely due to increased efficiency of production. Increasing efficiency is therefore a key component of agricultural GHG mitigation. Increasing efficiency,while essential, may not be enough on its own. New technologies are therefore needed and for ruminant livestock there are some promising products; compounds that inhibit enteric CH4, vaccines, low emitting sheep have been successfully bred and, a variety of low emitting feeds, and feed additives.

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Progress in the development of vaccines against rumen methanogens

Cited by 50 publications

References 49 publications

Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol

Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol

Genome sequencing of rumen bacteria and archaea and its application to methane mitigation strategies

The Estimation and Mitigation of Agricultural Greenhouse Gas Emissions from Livestock

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