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Title: Horizontal gene transfer and evolution of antibiotic gene clusters
Author: Kallifidas, Dimitrios
ISNI:       0000 0001 3594 1132
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2001
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Genome sequencing projects from diverse bacteria and the release of genetically engineered microorganisms make the topic of horizontal gene transfer (HGT) fashionable. Sequence analysis indicates the high frequency and the importance of horizontal gene transfer to the microbial evolution. Much knowledge about horizontal transfer has been derived from studies using soil microcosms, fluorescent-marked donors and recipients and from study of the increase of the antibiotic resistance as a result of use and often abuse of antibiotics. However, little is known about the transfer of chromosomally-located antibiotic biosynthesis genes in natural populations. The streptomycin pathway-specific regulator, strR, has been found in a set of diverse streptomycetes both phenotypically and genetically that previously have already been described to carry the resistance (strA) and one biosynthetic (strBl) gene from the same cluster. Phylogenetic analysis of both 16S rRNA and trpB gene fragments showed that two isolates were closely related to S. coelicolor which are known not to produce streptomycin or to contain any biosynthesis or resistance genes. The remaining pair did appear to be closely related to each other, particularly from the trpB analysis. trpB gene proved to be useful for resolving phylogenetic relationships between strains with highly conserved gamma region of the 16S rRNA gene. However, one of these strains is the only one from the S. griseus distant isolates that produced streptomycin and possessed many other genes from the cluster. The phylogenetic incongruency between `species' tree and `gene' tree can be attributed to horizontal gene transfer. The sequence identity of the detected genes is extremely high (99%) indicating a recent transfer event. Besides the physical proximity of strRABl genes, there is also a well-characterised functional correlation of these genes in the streptomycin producer, S. griseus. However, strRA genes are silent in coelicolor-like isolates ASSF15 and ASB37. Therefore, this transfer may have other ecological role than a simple resistance phenotype such as the evolution of antibiotic cluster. It was not possible to prove the integration site of strRABl genes within ASB37 genome but a possible site was identified. Pathway-specific regulator StrR activates the transcription of strBl and other genes from the streptomycin cluster by binding to the upstream promoter regions. This protein binds as a tetramer. N-terminal deleted StrR derivatives were still able to bind as pseudodimers (two monomers). Two putative domains in the N'-terminus of the protein responsible for the protein dimerisation during the binding process have been identified.
Supervisor: Not available Sponsor: Schering-Plough Corporation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR Microbiology Biomedical engineering Biochemical engineering Microbiology