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Mutagenic DNA repair genes on plasmids from the 'pre-antibiotic era'
S G Sedgwick1, S M Thomas, V M Hughes
1Genetics Division, National Institute for Medical Research, London, UK.
Abstract:
Resistance transfer factors are natural conjugative plasmids encoding antibiotic resistance. Some also encode mutagenic DNA repair genes giving resistance to DNA damage and induced mutagenesis. It has been shown that antibiotic resistance has been acquired by recent transposition events; however, we show here that mutagenic repair genes existed much earlier on these types of plasmids. Conjugative plasmids from eight incompatibility groups from the Murray collection of 'pre-antibiotic era' enterobacteria were tested for complementation of mutagenic repair-deficient Escherichia coli umuC36. Although none of these plasmids carry transposon-encoded drug resistance genes, IncI1 and IncB plasmids were identified which restored ultraviolet resistance and induced mutability to umuC36 mutants. Furthermore they increased the UV resistance and induced mutability of wild-type E. coli, Klebsiella aerogenes and Citrobacter intermedius, thus showing that they could confer a general selective advantage to a variety of hosts. Like known mutagenic repair genes, complementation by these plasmid genes required the SOS response of the host cell. Nucleotide hybridisation showed that these plasmids harboured sequences similar to the impCAB locus, the mutagenic repair operon of modern-day IncI1 plasmids. The evolution of mutagenic repair genes is discussed.
Insights
Mutagenic repair genes, conferring resistance to DNA damage, were found on ancient plasmids predating antibiotic resistance. These genes provided a selective advantage to bacteria even before the antibiotic era.
Area of Science:
- Microbiology
- Molecular Biology
- Evolutionary Biology
Background:
- Resistance transfer factors are conjugative plasmids that can carry antibiotic resistance genes.
- Some plasmids also encode mutagenic DNA repair genes, offering resistance to DNA damage and induced mutagenesis.
- While antibiotic resistance acquisition is linked to recent transposition, the evolutionary history of mutagenic repair genes on plasmids is less understood.
Purpose of the Study:
- To investigate the presence and function of mutagenic repair genes on plasmids from the pre-antibiotic era.
- To determine if these ancient plasmids could confer resistance to DNA damage and enhance mutagenesis.
- To understand the evolutionary origins of mutagenic repair genes on conjugative plasmids.
Main Methods:
- Testing pre-antibiotic era conjugative plasmids for complementation of mutagenic repair-deficient Escherichia coli (umuC36).
- Assessing the impact of these plasmids on ultraviolet (UV) resistance and induced mutability in both mutant and wild-type bacterial strains.
- Utilizing nucleotide hybridization to identify sequences homologous to known mutagenic repair operons.
Main Results:
- IncI1 and IncB plasmids from the Murray collection restored UV resistance and induced mutability to umuC36 mutants.
- These plasmids enhanced UV resistance and induced mutability in wild-type E. coli, Klebsiella aerogenes, and Citrobacter intermedius.
- The identified plasmids contained sequences similar to the impCAB locus, the mutagenic repair operon of modern IncI1 plasmids.
- Complementation by these plasmid genes was dependent on the host cell's SOS response.
Conclusions:
- Mutagenic repair genes were present on conjugative plasmids much earlier than previously thought, existing before the widespread use of antibiotics.
- These ancient genes provided a selective advantage to bacteria by increasing resistance to DNA damage and mutagenesis.
- The findings shed light on the early evolution of DNA repair mechanisms and their integration into mobile genetic elements.