Comprehensive analysis of IncC plasmid conjugation identifies a crucial role for the transcriptional regulator AcaB.
Nat Microbiol
; 5(11): 1340-1348, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32807890
ABSTRACT
The IncC family of broad-host-range plasmids enables the spread of antibiotic resistance genes among human enteric pathogens1-3. Although aspects of IncC plasmid conjugation have been well studied4-9, many roles of conjugation genes have been assigned based solely on sequence similarity. We applied hypersaturated transposon mutagenesis and transposon-directed insertion-site sequencing to determine the set of genes required for IncC conjugation. We identified 27 conjugation genes, comprising 19 that were previously identified (including two regulatory genes, acaDC) and eight not previously associated with conjugation. We show that one previously unknown gene, acaB, encodes a transcriptional regulator that has a crucial role in the regulation of IncC conjugation. AcaB binds upstream of the acaDC promoter to increase acaDC transcription; in turn, AcaDC activates the transcription of IncC conjugation genes. We solved the crystal structure of AcaB at 2.9-Å resolution and used this to guide functional analyses that reveal how AcaB binds to DNA. This improved understanding of IncC conjugation provides a basis for the development of new approaches to reduce the spread of these multi-drug-resistance plasmids.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Plasmídeos
/
Fatores de Transcrição
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Transativadores
/
Conjugação Genética
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Proteínas de Escherichia coli
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Microbiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Austrália