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Complex Multilevel Control of Hemolysin Production by Uropathogenic Escherichia coli
Nguyen Thi Khanh Nhu1,2, Minh-Duy Phan1,2, Brian M Forde1,2,3
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
Mbio
|October 3, 2019
Summary
Uropathogenic Escherichia coli (UPEC) hemolysin gene variation correlates with phylogenetic lineage and multidrug resistance. New genes controlling hemolysin secretion, including those in LPS biosynthesis and chaperone activity, were identified.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Uropathogenic Escherichia coli (UPEC) causes most urinary tract infections and sepsis.
- Hemolysin is a key UPEC virulence factor, produced by nearly half of strains.
- Hemolysin gene (hlyA) prevalence varies significantly across E. coli sequence types (STs).
Purpose of the Study:
- To investigate hemolysin sequence diversity within the ST131 E. coli clone.
- To identify genes regulating hemolysin production and secretion.
- To correlate hemolysin activity with phylogenetic and antimicrobial resistance profiles.
Main Methods:
- Phylogenetic analysis of the hlyCABD operon in E. coli STs.
- Genome sequencing of the ST131 clade C2 strain S65EC.
- Genome-wide screen using transposon mutagenesis and Tn-seq for hemolysin activity.
- Targeted mutagenesis and complementation assays.
Main Results:
- Hemolysin gene sequence variation aligns with phylogenetic designations within ST131.
- Strongest hemolytic activity in ST131 is linked to the multidrug-resistant clade C2 sublineage.
- Thirteen genes, including those for LPS inner core biosynthesis (waaC, waaF, waaG, rfaE) and chaperone activity (dnaK, dnaJ), are essential for hemolysin production and secretion.
Conclusions:
- Hemolysin regulation in UPEC involves a complex, multilevel system.
- LPS biosynthesis and chaperone proteins play critical roles in hemolysin secretion.
- Understanding hemolysin diversity and regulation enhances knowledge of UPEC virulence and pathogenesis.
