Identification of Novel Thermosensors in Gram-Positive Pathogens

FERNÁNDEZ, PILAR; DÍAZ, ALEJANDRA RAQUEL; RÉ, MARÍA FLORENCIA; PORRINI, LUCÍA; DE MENDOZA, DIEGO; ALBANESI, DANIELA; MANSILLA, MARÍA CECILIA

Frontiers in Molecular Biosciences

Frontiers

Año: 2020 vol. 7

Temperature is a crucial variable that every living organism, from bacteria to humans,need to sense and respond to in order to adapt and survive. In particular, pathogenicbacteria exploit host-temperature sensing as a cue for triggering virulence geneexpression. Here, we have identified and characterized two integral membranethermosensor histidine kinases (HKs) from Gram-positive pathogens that exhibit highsimilarity to DesK, the extensively characterized cold sensor histidine kinase fromBacillus subtilis. Through in vivo experiments, we demonstrate that SA1313 fromStaphylococcus aureus and BA5598 from Bacillus anthracis, which likely control theexpression of putative ATP binding cassette (ABC) transporters, are regulated byenvironmental temperature. We show here that these HKs can phosphorylate the noncognateresponse regulator DesR, partner of DesK, both in vitro and in vivo, inducing inB. subtilis the expression of the des gene upon a cold shock. In addition, we report thecharacterization of another DesK homolog from B. subtilis, YvfT, also closely associatedto an ABC transporter. Although YvfT phosphorylates DesR in vitro, this sensor kinasecan only induce des expression in B. subtilis when overexpressed together with itscognate response regulator YvfU. This finding evidences a physiological mechanismto avoid cross talk with DesK after a temperature downshift. Finally, we present datasuggesting that the HKs studied in this work appear to monitor different rangesof membrane lipid properties variations to mount adaptive responses upon cooling.Overall, our findings point out that bacteria have evolved sophisticated mechanismsto assure specificity in the response to environmental stimuli. These findings pave theway to understand thermosensing mediated by membrane proteins that could haveimportant roles upon host invasion by bacterial pathogens.