BREAD: Toward Development of a Vaccine for Contagious Bovine Pleuropneumonia (CBPP)

BREAD: Toward Development of a Vaccine for Contagious Bovine Pleuropneumonia (CBPP)

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Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subspecies mycoides (Mmm), is an economically very important livestock disease within Africa that limits the availability of protein sources for nutrition and restricts trade. The current control relies on a live vaccine that has shortcomings, such as, limited efficacy and short duration of immunity. International efforts to create a vaccine to protect against CBPP have been thwarted because of an almost complete lack of genetic tools for this species. As a result, it has been difficult to apply the tools of modern biology to this pressing African need. In this project, the J. Craig Venter Institute (JCVI) joins forces with the International Livestock Research Institute (ILRI) in Kenya and the National Institute for Agronomical Research (INRA) in France to explore the use of new synthetic biology technologies to genetically manipulate Mmm genomes with the ultimate goal of creating strains that can be developed as live vaccine derivatives and identifying virulence traits using subsequent in vitro and in vivo assays.

These JCVI synthetic biology approaches are a transformational advance in our ability to design and engineer novel bacteria with extraordinary properties to serve human needs. Since previous JCVI work including the creation of the synthetic cell was done using a closely related species to Mmm, Mycoplasma mycoides subsp. capri (Mmc), and synthetic biology tools were developed for this species, JCVI will continue its work with Mmc during the course of this project. INRA will develop the synthetic biology tools for Mmm as well as the pneumonia-causing strain of Mmc and ILRI will implement the tools and test mutants using in vitro and in vivo assays.

While our long-term perspective is to use key synthetic biology technologies to produce a safe and efficient Mmm vaccine strain by rationally modifying its genome, the current project is meant to lay the foundation for the development of a modern CBPP vaccine. Together, we will expand the mycoplasma toolbox using Mmc as a model in order to enhance our capacity to produce modern Mmm vaccines. We will also establish a caprine model for pulmonary mycoplasma infections with the available tools using the closely related pathogen Mmc.

Publications

Impact of donor-recipient phylogenetic distance on bacterial genome transplantation.
Nucleic acids research. 2016-09-30; 44.17: 8501-11.
PMID: 27488189
MIB-MIP is a mycoplasma system that captures and cleaves immunoglobulin G.
Proceedings of the National Academy of Sciences of the United States of America. 2016-05-10; 113.19: 5406-11.
PMID: 27114507
Complete Genome Sequence of Mycoplasma mycoides subsp. mycoides T1/44, a Vaccine Strain against Contagious Bovine Pleuropneumonia.
Genome announcements. 2016-04-14; 4.2:
PMID: 27081135
In-Yeast Engineering of a Bacterial Genome Using CRISPR/Cas9.
ACS synthetic biology. 2016-01-15; 5.1: 104-9.
PMID: 26592087
Galactofuranose in Mycoplasma mycoides is important for membrane integrity and conceals adhesins but does not contribute to serum resistance.
Molecular microbiology. 2016-01-01; 99.1: 55-70.
PMID: 26354009
High quality draft genomes of the Mycoplasma mycoides subsp. mycoides challenge strains Afadé and B237.
Standards in genomic sciences. 2015-01-01; 10.89.
PMID: 26516405
TREC-IN: gene knock-in genetic tool for genomes cloned in yeast.
BMC genomics. 2014-12-24; 15.1180.
PMID: 25539750
Synthetic genomics: potential and limitations.
Current opinion in biotechnology. 2012-10-01; 23.5: 659-65.
PMID: 22342755

Funding

Funding for this project provided by NSF-BREAD IOS 1110151.