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Evolution of the leukotoxin promoter in genus Mannheimia.

Larsen J, Pedersen AG, Davies RL, Kuhnert P, Frey J, Christensen H, Bisgaard M, Olsen JE - BMC Evol. Biol. (2009)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark. jesl@life.ku.dk

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

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Alignment of the CP region. The alignment of the intergenic regions upstream of the lkt 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 (CP region), with the notable exception of the region corresponding to the repeat tract in M. haemolytica serotype A1 [22], which accommodated many sequence variations. Capital letters denote aligned residues. Lower-case letters are not considered to be aligned. Numbers (0–9) below the alignment reflect the relative degree of local similarity among the sequences. Previous works [18,22,23] allowed us to infer cis-regulatory sequences. The footprinted palindromic motifs are indicated by an over line. The repeat sequences are enclosed by a rectangle. The core promoter including the -10 hexamer, the extended TG motifs, and the transcription start site (+1) is highlighted. Mh, M. haemolytica: Mgl; M. glucosida; Mr, M. ruminalis; Mgr, M. granulomatis; Mv, M. varigena.
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Figure 2: Alignment of the CP region. The alignment of the intergenic regions upstream of the lkt 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 (CP region), with the notable exception of the region corresponding to the repeat tract in M. haemolytica serotype A1 [22], which accommodated many sequence variations. Capital letters denote aligned residues. Lower-case letters are not considered to be aligned. Numbers (0–9) below the alignment reflect the relative degree of local similarity among the sequences. Previous works [18,22,23] allowed us to infer cis-regulatory sequences. The footprinted palindromic motifs are indicated by an over line. The repeat sequences are enclosed by a rectangle. The core promoter including the -10 hexamer, the extended TG motifs, and the transcription start site (+1) is highlighted. Mh, M. haemolytica: Mgl; M. glucosida; Mr, M. ruminalis; Mgr, M. granulomatis; Mv, M. varigena.

Mentions: The alignment revealed 100% identity over the entire 406-bp intergenic region from M. haemolytica serotype A1 str. PHL101 and str. PHL213 (data not shown) and previous reports [18,22,23] allowed us to infer cis-regulatory sequences. The 406-bp region was shared among M. haemolytica serotype A2 and M. glucosida serotype A11 as reflected in Figure 1. The alignment 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 (CP region), with the notable exception of the region corresponding to the repeat tract in M. haemolytica serotype A1 [22], which accommodated many sequence variations (Figures 1 and 2).


Evolution of the leukotoxin promoter in genus Mannheimia.

Larsen J, Pedersen AG, Davies RL, Kuhnert P, Frey J, Christensen H, Bisgaard M, Olsen JE - BMC Evol. Biol. (2009)

Alignment of the CP region. The alignment of the intergenic regions upstream of the lkt 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 (CP region), with the notable exception of the region corresponding to the repeat tract in M. haemolytica serotype A1 [22], which accommodated many sequence variations. Capital letters denote aligned residues. Lower-case letters are not considered to be aligned. Numbers (0–9) below the alignment reflect the relative degree of local similarity among the sequences. Previous works [18,22,23] allowed us to infer cis-regulatory sequences. The footprinted palindromic motifs are indicated by an over line. The repeat sequences are enclosed by a rectangle. The core promoter including the -10 hexamer, the extended TG motifs, and the transcription start site (+1) is highlighted. Mh, M. haemolytica: Mgl; M. glucosida; Mr, M. ruminalis; Mgr, M. granulomatis; Mv, M. varigena.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2697988&req=5

Figure 2: Alignment of the CP region. The alignment of the intergenic regions upstream of the lkt 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 (CP region), with the notable exception of the region corresponding to the repeat tract in M. haemolytica serotype A1 [22], which accommodated many sequence variations. Capital letters denote aligned residues. Lower-case letters are not considered to be aligned. Numbers (0–9) below the alignment reflect the relative degree of local similarity among the sequences. Previous works [18,22,23] allowed us to infer cis-regulatory sequences. The footprinted palindromic motifs are indicated by an over line. The repeat sequences are enclosed by a rectangle. The core promoter including the -10 hexamer, the extended TG motifs, and the transcription start site (+1) is highlighted. Mh, M. haemolytica: Mgl; M. glucosida; Mr, M. ruminalis; Mgr, M. granulomatis; Mv, M. varigena.
Mentions: The alignment revealed 100% identity over the entire 406-bp intergenic region from M. haemolytica serotype A1 str. PHL101 and str. PHL213 (data not shown) and previous reports [18,22,23] allowed us to infer cis-regulatory sequences. The 406-bp region was shared among M. haemolytica serotype A2 and M. glucosida serotype A11 as reflected in Figure 1. The alignment 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 (CP region), with the notable exception of the region corresponding to the repeat tract in M. haemolytica serotype A1 [22], which accommodated many sequence variations (Figures 1 and 2).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark. jesl@life.ku.dk

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus