Population genomic analysis of Mycoplasma bovis elucidates geographical variations and genes associated with host types

Authors: KUMAR, ROSHAN - South Dakota State University; Register, Karen; CHRISTOPHER-HENNINGS, JANE - South Dakota State University; MORONI, PAOLO - Cornell University; GIOIA, GLORIA - Cornell University; GARCIA-FERNANDEZ, NURIA - South Dakota State University; NELSON, JULIA - South Dakota State University; JELINSKI, MURRAY - University Of Saskatchewan; LYSNYANSKY, INNA - Kimron Veterinary Institute; Bayles, Darrell; Alt, David; SCARIA, JOY - South Dakota State University

Submitted to: Microorganisms
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2020
Publication Date: 10/10/2020
Citation: Kumar, R., Register, K.B., Christopher-Hennings, J., Moroni, P., Gioia, Gloria, Garcia-Fernandez, N., Nelson, J., Jelinski, M., Lysnyansky, I., Bayles, D.O., Alt, D.P., Scaria, J. 2020. Population genomic analysis of Mycoplasma bovis elucidates geographical variations and genes associated with host types. Microorganisms. 8(10). Article 1561. https://doi.org/10.3390/microorganisms8101561.
DOI: https://doi.org/10.3390/microorganisms8101561

Interpretive Summary: Disease resulting from Mycoplasma bovis causes significant economic loss in the cattle industry worldwide and in the North American bison industry. Since antibiotic treatment is ineffective and no efficacious vaccine is available, mycoplasmosis is primarily controlled by herd management measures such as restrictions on movements and culling of infected animals. Development of an effective vaccine has been hampered by a lack of knowledge regarding key genetic differences and the extent of diversity among M. bovis strains. To address this gap, we sequenced the genomes of 147 isolates from diverse geographic locations, with two obtained from deer and the rest from cattle and bison. We combined those data with publically available genome sequences from an additional 104 isolates and performed a large-scale, comparative analysis of the 251 M. bovis genomes. Our results indicate that M. bovis possesses an unexpectedly high degree of genetic diversity. A family tree based on genome sequences reveals six major lineages. Relationships among different lineages are consistent with trans-continental transmission of strains. Isolates from Australia, China and Israel are more closely related to one another than to isolates from other world regions. We found no association between any particular family of isolates and the host of origin. However, our analyses indicate that one member of a family of virulence-related proteins is strongly associated with only bovine isolates. Results from this study provide a global picture of the population structure of M. bovis and identify specific genes that may be useful targets for diagnostics and vaccine development.

Technical Abstract: Among more than twenty species belonging to the class Mollecutes, Mycoplasma bovis is the most common cause of bovine mycoplasmosis in North America and Europe. Bovine mycoplasmosis causes significant economic loss in the cattle industry. The number of M. bovis positive herds has recently increased in North America and Europe. Since antibiotic treatment is ineffective and no efficient vaccine is available, M. bovis-induced mycoplasmosis is primarily controlled by herd management measures such as the restriction of moving infected animals out of the herds and culling of infected animals or shedders. To better understand the population structure and genomic factors that may contribute to its transmission, we sequenced 147 M. bovis strains isolated from four different countries and hosts, primarily cattle. We performed a large-scale comparative analysis of M. bovis genomes by integrating 104 publicly available genomes and our dataset (251 total genomes). A whole genome-single nucleotide polymorphism (SNP)-based phylogeny revealed that M. bovis population structure is composed of five clades with one of the isolates clustering with the outgroup M. agalactiae. These isolates were found to cluster with those from Canada, Switzerland, Israel, and Lithuania, suggesting trans-continental transmission of the strains. We also validated a previous report suggesting minimum divergence in isolates of Australian origin, which grouped within a single clade along with strains from China and Israel. However, no observable pattern of host association in M. bovis genomes was found in this study. Our comparative genome analysis also revealed that M. bovis has an open pangenome with a large breadth of unexplored diversity of genes. Analysis of vsp gene-host association revealed a single vsp significantly associated with bovine isolates that may be targeted for diagnostics or vaccine development. Our study also found that M. bovis genome harbors a large number of IS elements, including a novel 1624 bp IS element, ISMbov9. Collectively, the genome data and the whole genome-based population analysis in this study may help to develop control measures to reduce the incidence of M. bovis-induced mycoplasmosis in cattle and/or to identify candidate genes for vaccine development.