Population Genomic Analysis of Mycoplasma bovis Elucidates Geographical Variations and Genes associated with Host-Types

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 recently has 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 or shedders of M. bovis. 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 viz. USA (n = 121), Canada (n = 22), Israel (n = 3) and Lithuania (n = 1). All except two of the isolates (KRB1 and KRB8) were isolated from two host types i.e., bovine (n = 75) and bison (n = 70). We performed a large-scale comparative analysis of M. bovis genomes by integrating 103 publicly available genomes and our dataset (250 total genomes). Whole genome single nucleotide polymorphism (SNP) based phylogeny using M. agalactiae as an outgroup revealed that M. bovis population structure is composed of five different clades. USA isolates showed a high degree of genomic divergence in comparison to the Australian isolates. Based on host of origin, all the isolates in clade IV was of bovine origin, whereas majority of the isolates in clades III and V was of bison origin. Our comparative genome analysis also revealed that M. bovis has an open pangenome with a large breadth of unexplored diversity of genes. The function based analysis of autogenous vaccine candidates (n = 10) included in this study revealed that their functional diversity does not span the genomic diversity observed in all five clades identified in this study. Our study also found that M. bovis genome harbors a large number of IS elements and their number increases significantly (p = 7.8x10-6) as the genome size increases. Collectively, the genome data and the whole genome-based population analysis in this study may help to develop better understanding of M. bovis induced mycoplasmosis in cattle.

Application of Four Genotyping Methods to Mycoplasma bovis Isolates Derived from Western Canadian Feedlot Cattle

“…While Canada’s feedlot sector is concentrated in Alberta, there is bilateral trade in cattle between Canada and the United States, which is noteworthy because five isolates from American cattle were evenly distributed among the Canadian isolates within the NJ trees and MSTs (identified in Table S1 in the supplemental material). These results support the findings of a recent study in which wgSNV analysis found a high degree of genetic diversity among the American isolates, with Canadian isolates clustering within the same clade as the American isolates ( 32 ).…”

“…This level of resolution led the researchers to conclude that a single strain of M. bovis was circulating within Australia’s cattle population. This is quite unique, since a number of other country-level studies have found multiple clusters of genetically distant M. bovis STs within the cattle population ( 30 – 32 , 48 ). Furthermore, these studies provided some insight into the movement of specific STs from country to country and over time.…”

“…There was a clear genetic distinction between the isolates from Europe and Australia, and a dominant genotype was associated with mastitis. wgSNV analysis has also been used to compare the relatedness of 250 M. bovis isolates originating from seven countries ( 32 ). These isolates formed six clades, with U.S. isolates exhibiting the greatest genetic diversity but also clustering with Canadian isolates.…”

Genome mosaicism in field strains of Mycoplasma bovis as footprints of in-host horizontal chromosomal transfer

“…Other studies reported decreasing diversity and mono-clonal spread in several countries (22,(36)(37)(38). The existence of lineages with a high level of genetic diversity and others with low diversity has been described at worldwide scale (39,40). This situation is not limited to M. bovis and has been observed in other mycoplasmas like in small ruminants with M. agalactiae (41,42) where ovine isolates are described as more clonal whereas caprine are more variable (43).…”

Serological evidence for historical and present-day exposure of North American bison to Mycoplasma bovis

“…Thus, a fuller understanding of the molecular events that andmay have contributed to the emergence of mycoplasmosis in bison requires more extensive genetic characterization of bison isolates. To this end, we have recently sequenced the genomes of a total of 82 bison isolates, 55 from the United States and 27 from Canada, that collectively represent all STs known at this time to infect bison [ 20 , 21 ]. Comprehensive genome-wide analyses, including comparison with data available for cattle isolates, are currently underway.…”