The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

MSphere
Jozef DingemansKarin Sauer

Abstract

The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residue...Continue Reading

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Citations

Nov 9, 2018·World Journal of Microbiology & Biotechnology·Tapas DasUtpal Ch De
May 9, 2019·Future Microbiology·Aimee Rp Tierney, Philip N Rather
Apr 13, 2019·International Journal of Molecular Sciences·Anjali Y BhagirathKangmin Duan
Jul 11, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·C E LopesF M Siqueira

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Methods Mentioned

BETA
two-component
metal oxide affinity chromatography

Software Mentioned

TMHMM
Prism5 Pad
SagS
COMSTAT
PHYRE2 Protein Fold Recognition Server
PHYRE2
Prism5
Rosetta
ImageJ

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