Evolution of the leukotoxin promoter in genus Mannheimia

Jesper Larsen,Peter Kuhnert,John E Olsen,Magne Bisgaard,Anders G Pedersen,Joachim Frey,Robert L Davies,Henrik Christensen

doi:10.1186/1471-2148-9-121

Abstract

BackgroundThe Mannheimia species encompass a wide variety of bacterial lifestyles, including opportunistic pathogens and commensals of the ruminant respiratory tract, commensals of the ovine rumen, and pathogens of the ruminant integument. Here we present a scenario for the evolution of the leukotoxin promoter among representatives of the five species within genus Mannheimia. We also consider how the evolution of the leukotoxin operon fits with the evolution and maintenance of virulence.ResultsThe alignment of the intergenic regions upstream of the leukotoxin genes showed significant sequence and positional conservation over a 225-bp stretch immediately proximal to the transcriptional start site of the lktC gene among all Mannheimia strains. However, in the course of the Mannheimia genome evolution, the acquisition of individual noncoding regions upstream of the conserved promoter region has occurred. The rate of evolution estimated branch by branch suggests that the conserved promoter may be affected to different extents by the types of natural selection that potentially operate in regulatory regions. Tandem repeats upstream of the core promoter were confined to M. haemolytica with a strong association between the sequence of the repeat units, the number of repeat units per promoter, and the phylogenetic history of this species.ConclusionThe mode of evolution of the intergenic regions upstream of the leukotoxin genes appears to be highly dependent on the lifestyle of the bacterium. Transition from avirulence to virulence has occurred at least once in M. haemolytica with some evolutionary success of bovine serotype A1/A6 strains. Our analysis suggests that changes in cis-regulatory systems have contributed to the derived virulence phenotype by allowing phase-variable expression of the leukotoxin protein. We propose models for how phase shifting and the associated virulence could facilitate transmission to the nasopharynx of new hosts.

Highlights

The Mannheimia species encompass a wide variety of bacterial lifestyles, including opportunistic pathogens and commensals of the ruminant respiratory tract, commensals of the ovine rumen, and pathogens of the ruminant integument
Pulmonary infection caused by M. haemolytica serotype A1 is considered to be non-communicable and the continuous circulation of these bacteria in bovine populations seems to depend on their capacity for asymptomatic transmission to the nasopharynx, and not the lungs, of new hosts [7]
This measure of similarity is based on 16S rRNA phylogenies [1,20] and on relationships resolved by multilocus enzyme electrophoresis (MLEE) typing within M. haemolytica + M. glucosida [2]

Summary

Introduction

The Mannheimia species encompass a wide variety of bacterial lifestyles, including opportunistic pathogens and commensals of the ruminant respiratory tract, commensals of the ovine rumen, and pathogens of the ruminant integument. The majority of strains isolated from pulmonary infection in cattle belongs to M. haemolytica serotype A1/A6 [2] These strains are sub-dominant to other serotypes (e.g., bovine serotype A2 strains) in the nasopharynx of healthy cattle but dominate when the host defences are at least partly compromised [3,4,5]. Pulmonary infection caused by M. haemolytica serotype A1 is considered to be non-communicable (i.e. no direct transmission between the lungs) and the continuous circulation of these bacteria in bovine populations seems to depend on their capacity for asymptomatic transmission to the nasopharynx, and not the lungs, of new hosts [7]. Bovine strains of M. varigena biogroup 6, which is the most basal of the Mannheimia species, colonise the nasopharynx asymptomatically, they have the propensity to cause disease [1]. It seems reasonable to conclude that the genes responsible for the virulence of Mannheimia strains must evolve in response to the demands (selection pressures) associated with a commensal lifestyle rather than any advantages that might arise from causing disease

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Conclusion