Sequence Diversity and Molecular Evolution of the Leukotoxin ( lktA ) Gene in Bovine and Ovine Strains of Mannheimia ( Pasteurella ) haemolytica

Abstract

The molecular evolution of the leukotoxin structural gene (lktA) of Mannheimia (Pasteurella) haemolytica was investigated by nucleotide sequence comparison of lktA in 31 bovine and ovine strains representing the various evolutionary lineages and serotypes of the species. Eight major allelic variants (1.4 to 15.7% nucleotide divergence) were identified; these have mosaic structures of varying degrees of complexity reflecting a history of horizontal gene transfer and extensive intragenic recombination. The presence of identical alleles in strains of different genetic backgrounds suggests that assortative (entire gene) recombination has also contributed to strain diversification in M. haemolytica. Five allelic variants occur only in ovine strains and consist of recombinant segments derived from as many as four different sources. Four of these alleles consist of DNA (52.8 to 96.7%) derived from the lktA gene of the two related species Mannheimia glucosida and Pasteurella trehalosi, and four contain recombinant segments derived from an allele that is associated exclusively with bovine or bovine-like serotype A2 strains. The two major lineages of ovine serotype A2 strains possess lktA alleles that have very different evolutionary histories and encode divergent leukotoxins (5.3% amino acid divergence), but both contain segments derived from the bovine allele. Homologous segments of donor and recipient alleles are identical or nearly identical, indicating that the recombination events are relatively recent and probably postdate the domestication of cattle and sheep. Our findings suggest that host switching of bovine strains from cattle to sheep, together with inter-and intraspecies recombinational exchanges, has played an important role in generating leukotoxin diversity in ovine strains. In contrast, there is limited allelic diversity of lktA in bovine strains, suggesting that transmission of strains from sheep to cattle has been less important in leukotoxin evolution.Mannheimia haemolytica is the etiological agent of bovine and ovine pneumonic pasteurellosis, a disease that causes considerable economic losses to the cattle and sheep industries (17,20). Capsular serotyping provides the primary basis for the classification of strains and epidemiological typing of M. haemolytica, which has traditionally been subdivided into 13 serotypes (1, 49). The association of different serotypes with infections of cattle and sheep (17,20) suggests that serotype-related strain differences occur in host specificity and virulence. For example, serotype A1 and A6 strains account for almost all cases of bovine pneumonic pasteurellosis, whereas serotype A2 and A7 isolates are the major causes of disease in sheep. It has also been shown that bovine and ovine isolates of the same serotype, e.g., A1, A2, or A6, can be distinguished by differences in chromosomal genotype (13) or outer membrane protein (OMP) profiles (10). The inference is that natural populations of M. haemolytica consist of distinct evolutionary lineages that are differentia...

Acute Die-off of Chamois (Rupicapra rupicapra) in the Eastern Austrian Alps due to Bacterial Bronchopneumonia withPasteurellaceae

“…No other pathogen (virus or bacteria) was detected, and we are confident that the Pasteurellaceae isolated was the most likely cause of disease. This conclusion is supported by two lktA-positive isolates most closely related to the type strain of M. glucosida; lktA is a fundamental virulence factor in the pathogenesis of pneumonic pasteurellosis (Davies et al 2001).…”

“…Phylogenetic analyses were conducted using MEGA 5 (Tamura et al 2011). All isolates were screened for the gene encoding leukotoxin (lktA) by PCR (Davies et al 2001).…”

Análisis Genómico de Mannheimia haemolytica Serotipo A2 para la Identificación de Potenciales Candidatos Vacunales contra la Neumonía en Alpacas

“…Mannheimia haemolytica comprende 12 serotipos capsulares (Angen et al, 1999), siendo A1 y A6 los serotipos más aislados en casos de procesos neumónicos en bovinos (Davies et al, 2001), en tanto que A2 es en ovinos (Saadati et al, 1997), aunque también se observa un incremento en la prevalencia de los serotipos A5, A6 y A7 (Ewers et al, 2004); sin embargo, se desconoce los serotipos asociados a los casos neumónicos en crías de alpacas.…”

Human Wound Infection with Mannheimia glucosida following Lamb Bite

“…Leukotoxin is a known virulence factor for M. haemolytica (14). It is a member of the RTX (repeats-in-toxin) family of cytotoxins (15) produced by a number of Gram-negative bacterial species, including Escherichia coli, Actinobacillus pleuropneumoniae, and Aggregatibacter actinomycetemcomitans (16).…”

“…It is a member of the RTX (repeats-in-toxin) family of cytotoxins (15) produced by a number of Gram-negative bacterial species, including Escherichia coli, Actinobacillus pleuropneumoniae, and Aggregatibacter actinomycetemcomitans (16). The leukotoxin operon consists of four genes, designated lktC, lktA, lktB, and lktD (17), and aids in bacterial survival by interacting with the alveolar macrophages, neutrophils, and lymphocytes (5,14).…”