Comprehensive analysis of type 1 fimbriae regulation in fimB-null strains from the multidrug resistant Escherichia coli ST131 clone.
Uropathogenic Escherichia coli (UPEC) of sequence type 131 (ST131) are a pandemic multidrug resistant clone associated with urinary tract and bloodstream infections. Type 1 fimbriae, a major UPEC virulence factor, are essential for ST131 bladder colonization. The globally dominant sub-lineage of ST131 strains, clade C/H30-R, possess an ISEc55 insertion in the fimB gene that controls phase-variable type 1 fimbriae expression via the invertible fimS promoter. We report that inactivation of fimB in these strains causes altered regulation of type 1 fimbriae expression. Using a novel read-mapping approach based on Illumina sequencing, we demonstrate that 'off' to 'on' fimS inversion is reduced in these strains and controlled by recombinases encoded by the fimE and fimX genes. Unlike typical UPEC strains, the nucleoid-associated H-NS protein does not strongly repress fimE transcription in clade C ST131 strains. Using a genetic screen to identify novel regulators of fimE and fimX in the clade C ST131 strain EC958, we defined a new role for the guaB gene in the regulation of type 1 fimbriae and in colonisation of the mouse bladder. Our results provide a comprehensive analysis of type 1 fimbriae regulation in ST131, and highlight important differences in its control compared to non-ST131 UPEC.
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, 4059, Australia.
Sohinee
S
Sarkar
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Leah W
LW
Roberts
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Minh-Duy
MD
Phan
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Lendl
L
Tan
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Alvin W
AW
Lo
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Kate M
KM
Peters
Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.|Royal Brisbane and Women's Hospital, University of Queensland Centre for Clinical Research, Brisbane, Queensland, 4029, Australia.
David L
DL
Paterson
Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, PL4 8AA, UK.
Mathew
M
Upton
School of Medical Science, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, 4222, Australia.
Glen C
GC
Ulett
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia. s.beatson@uq.edu.au.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia. s.beatson@uq.edu.au.
Scott A
SA
Beatson
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia. makrina.totsika@qut.edu.au.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia. makrina.totsika@qut.edu.au.|Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, 4059, Australia. makrina.totsika@qut.edu.au.
Makrina
M
Totsika
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia. m.schembri@uq.edu.au.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia. m.schembri@uq.edu.au.
Mark A
MA
Schembri
D000818:Animals; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D036781:Fimbriae Proteins / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D019426:Integrases / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000378:metabolism*; D056689:Uropathogenic Escherichia coli / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D011971:Receptors, Immunologic; D037521:Virulence Factors; C081956:fimB protein, E coli; C076610:fimbriae receptor, type 1; D036781:Fimbriae Proteins; D019426:Integrases