Signaling mechanism by the Staphylococcus aureus two-component system LytSR: role of acetyl phosphate in bypassing the cell membrane electrical potential sensor LytS

Abstract

The two-component system LytSR has been linked to the signal transduction of cell membrane electrical potential perturbation and is involved in the adaptation of Staphylococcus aureus to cationic antimicrobial peptides. It consists of a membrane-bound histidine kinase, LytS, which belongs to the family of multiple transmembrane-spanning domains receptors, and a response regulator, LytR, which belongs to the novel family of non-helix-turn-helix DNA-binding domain proteins. LytR regulates the expression of cidABC and lrgAB operons, the gene products of which are involved in programmed cell death and lysis. In vivo studies have demonstrated involvement of two overlapping regulatory networks in regulating the lrgAB operon, both depending on LytR. One regulatory network responds to glucose metabolism and the other responds to changes in the cell membrane potential. Herein, we show that LytS has autokinase activity and can catalyze a fast phosphotransfer reaction, with 50% of its phosphoryl group lost within 1 minute of incubation with LytR. LytS has also phosphatase activity. Notably, LytR undergoes phosphorylation by acetyl phosphate at a rate that is 2-fold faster than the phosphorylation by LytS. This observation is significant in lieu of the in vivo observations that regulation of the lrgAB operon is LytR-dependent in the presence of excess glucose in the medium. The latter condition does not lead to perturbation of the cell membrane potential but rather to the accumulation of acetate in the cell. Our study provides insights into the molecular basis for regulation of lrgAB in a LytR-dependent manner under conditions that do not involve sensing by LytS.

Role of the LytSR Two-Component Regulatory System in Staphylococcus lugdunensis Biofilm Formation and Pathogenesis

“…As lrg and cid operons are involved in autolysis and cell death (van den Esker et al, 2017), their transcription is subject to complex control. They are under the control of two overlapping regulatory networks, one in response to the metabolism of carbohydrates (Yang et al, 2005;Patel and Golemi-Kotra, 2015) and the other in response to changes in membrane potential (Patton et al, 2006).…”

Disruption of Two-component System LytSR Affects Forespore Engulfment in Bacillus thuringiensis

“…lrgAB is located downstream from the lytSR genes in Bt HD73 (Figure 1A ). The Bt lytS ( HD73_5856 , sensor histidine kinase), lytR ( HD73_5855 , response regulator), lrgA ( HD73_5854 , holin-like protein), and lrgB ( HD73_5853 , holin-like protein) genes encode proteins that share 50, 44, 44, and 54% amino acid sequence identity, respectively, with homologs in Staphylococcus aureus (Patel and Golemi-Kotra, 2015 ), and 66, 65, 62, and 78% amino acid sequence identity with homologs in B. subtilis (van den Esker et al, 2017 ). Alignments of these proteins from Bt, S. aureus , and B. subtilis are shown in Supplementary Figure 1 .…”

Responses of Acidobacteria Granulicella sp. WH15 to High Carbon Revealed by Integrated Omics Analyses

“…Another upregulated protein, LytR, is a sensory transduction protein that is part of the LytSR system, which in Staphylococcus aureus functions as a sensor-response system that detects perturbations in the electrical potential of the cell membrane, such as disturbances caused by the presence of stress agents [52]. Furthermore, the upregulation of tRNA genes could be involved in expression regulation.…”