Open Access Research article

Evolution of the leukotoxin promoter in genus Mannheimia

Jesper Larsen1*, Anders G Pedersen2, Robert L Davies3, Peter Kuhnert4, Joachim Frey4, Henrik Christensen1, Magne Bisgaard1 and John E Olsen1

Author Affiliations

1 Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark

2 Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Building 208, DK-2800 Lyngby, Denmark

3 Institute of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK

4 Institute of Veterinary Bacteriology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland

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BMC Evolutionary Biology 2009, 9:121  doi:10.1186/1471-2148-9-121

Published: 29 May 2009



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. 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.


The 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.


The 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.