Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2019 Jun 13;10:2586. doi: 10.1038/s41467-019-10556-8

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Fig. 7 — Model of GAS virulence regulation by environmental pH and SIP. At low-bacterial population density and near-neutral environmental pH (left panel), the deprotonated side chain of H144 destabilizes the intramolecular interactions with Y176, Y182’, and E185’. The weakened interactions at the base of the SIP-binding pocket inhibit high-affinity RopB–SIP interactions resulting in defective RopB–DNA interactions and decreased RopB-dependent transcription activation of SIP and speB. At high-population density (right panel), environmental pH decreases to pH 5.5, resulting in acidification of the GAS cytosol. When the intracellular pH becomes closer to the pKa of histidine (pH ~6.2), the protonated side chain of RopB H144 facilitates the interactions with Y176, Y182’, and E185’. The stabilized intramolecular interactions at acidic pH promote high-affinity RopB–SIP interactions. The high-affinity RopB–DNA interactions and RopB polymerization aided by SIP binding leads to upregulation of SIP expression, which then triggers robust induction of SIP production by a positive feedback mechanism. Finally, SIP-dependent upregulation of speB results in secretion of SpeB zymogen (SpeB_Z). The acidified extracellular environment promotes rapid maturation of SpeB_Z to SpeB_M, and maximal protease activity of SpeB_M, facilitating disease progression by cleaving various host and GAS proteins²⁴