Journal article
The Sensor Histidine Kinase ArlS Is Necessary for Staphylococcus aureus To Activate ArlR in Response to Nutrient Availability
Journal of bacteriology, Vol.203(24), pp.e0042221-e0042221
11/19/2021
DOI: 10.1128/JB.00422-21
PMCID: PMC8604075
PMID: 34606376
Abstract
The ability of pathogens, including
Staphylococcus aureus
, to sense and adapt to diverse environments partially relies on two-component systems, such as ArlRS. Recent work revealed that the response regulator ArlR can be cross-activated by the sensor histidine kinase GraS, rendering the role of its cognate partner, ArlS, in response to manganese and glucose limitation uncertain.
ABSTRACT
Staphylococcus aureus
is a versatile opportunistic pathogen whose success is driven by its ability to adapt to diverse environments and host-imposed stresses. Two-component signal transduction systems, such as ArlRS, often mediate these adaptations. Loss of ArlRS or the response regulator ArlR alone impairs the ability of
S. aureus
to respond to host-imposed manganese starvation and glucose limitation. As sensor histidine kinases and response regulators frequently work as pairs, it has been assumed that ArlS senses and activates ArlR in response to these stimuli. However, recent work suggests that the sensor histidine kinase GraS can also activate ArlR, calling the contribution of ArlS in responding to manganese and glucose availability into question. The results of current studies reveal that ArlS is necessary to activate ArlR in response to manganese sequestration by the host immune effector calprotectin and glucose limitation. Although the loss of ArlS does not completely eliminate ArlR activity, this response regulator is no longer responsive to manganese or glucose availability in the absence of its cognate histidine kinase. Despite the residual activity of ArlR in the absence of ArlS, ArlR phosphorylation by ArlS is required for
S. aureus
to resist calprotectin-imposed metal starvation. Cumulatively, these findings contribute to the understanding of
S. aureus
signal transduction in response to nutritional immunity and support the previous observation indicating that ArlRS is activated by a common signal derived from host-imposed manganese and glucose limitation.
IMPORTANCE
The ability of pathogens, including
Staphylococcus aureus
, to sense and adapt to diverse environments partially relies on two-component systems, such as ArlRS. Recent work revealed that the response regulator ArlR can be cross-activated by the sensor histidine kinase GraS, rendering the role of its cognate partner, ArlS, in response to manganese and glucose limitation uncertain. The results of this study reveal that ArlS is necessary for the activation of ArlR in response to calprotectin and glucose limitation. Although a low level of ArlR activity remains in the absence of ArlS, ArlS phosphotransfer to ArlR is required for
S. aureus
to overcome calprotectin-induced nutritional stress. Collectively, this study provides fundamental information to understand how ArlRS mediates staphylococcal adaptation during infection.
Details
- Title: Subtitle
- The Sensor Histidine Kinase ArlS Is Necessary for Staphylococcus aureus To Activate ArlR in Response to Nutrient Availability
- Creators
- Paola K. Párraga Solórzano - University of Illinois Urbana-ChampaignAngela C. Shupe - University of Illinois Urbana-ChampaignThomas E. Kehl-Fie - University of Illinois Urbana-Champaign
- Contributors
- Michael J. Federle (Editor)
- Resource Type
- Journal article
- Publication Details
- Journal of bacteriology, Vol.203(24), pp.e0042221-e0042221
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JB.00422-21
- PMID
- 34606376
- PMCID
- PMC8604075
- ISSN
- 0021-9193
- eISSN
- 1098-5530
- Grant note
- name: Alice Helm Graduate Student Excellence Award; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R01 AI118880; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R01 AI155611; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R21 AI149115; DOI: 10.13039/100007204, name: Vallee Foundation
- Language
- English
- Date published
- 11/19/2021
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618523302771
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