scholarly journals Analysis of Two-Component Systems in Group B Streptococcus Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Cristina Faralla ◽  
Matteo M. Metruccio ◽  
Matteo De Chiara ◽  
Rong Mu ◽  
Kathryn A. Patras ◽  
...  
Keyword(s):  
Environmental Changes ◽  
Transcriptional Analysis ◽  
Transcriptional Responses ◽  
Component Systems ◽  
Two Component ◽  
Bacterial Fitness ◽  
Two Component Systems ◽  
Group B

ABSTRACTGroup BStreptococcus(GBS), in the transition from commensal organisms to pathogens, will encounter diverse host environments and, thus, require coordinated control of the transcriptional responses to these changes. This work was aimed at better understanding the role of two-component signal transduction systems (TCS) in GBS pathophysiology through a systematic screening procedure. We first performed a complete inventory and sensory mechanism classification of all putative GBS TCS by genomic analysis. Five TCS were further investigated by the generation of knockout strains, andin vitrotranscriptome analysis identified genes regulated by these systems, ranging from 0.1% to 3% of the genome. Interestingly, two sugar phosphotransferase systems appeared to be differentially regulated in the TCS-16 knockout strain (TCS loci were numbered in order of their appearance on the chromosome), suggesting an involvement in monitoring carbon source availability. High-throughput analysis of bacterial growth on different carbon sources showed that TCS-16 was necessary for the growth of GBS on fructose-6-phosphate. Additional transcriptional analysis provided further evidence for a stimulus-response circuit where extracellular fructose-6-phosphate leads to autoinduction of TCS-16, with concomitant dramatic upregulation of the adjacent operon, which encodes a phosphotransferase system. The TCS-16-deficient strain exhibited decreased persistence in a model of vaginal colonization. All mutant strains were also characterized in a murine model of systemic infection, and inactivation of TCS-17 (also known as RgfAC) resulted in hypervirulence. Our data suggest a role for the previously unknown TCS-16, here named FspSR, in bacterial fitness and carbon metabolism during host colonization, and the data also provide experimental evidence for TCS-17/RgfAC involvement in virulence.IMPORTANCETwo-component systems have been evolved by bacteria to detect environmental changes, and they play key roles in pathogenicity. A comprehensive analysis of TCS in GBS has not been performed previously. In this work, we classify 21 TCS and present evidence for the involvement of two specific TCS in GBS virulence and colonizationin vivo. Although pinpointing specific TCS stimuli is notoriously difficult, we used a combination of techniques to identify two systems with different effects on GBS pathogenesis. For one of the systems, we propose that fructose-6-phosphate, a metabolite in glycolysis, is sufficient to induce a regulatory response involving a sugar transport system. Our catalogue and classification of TCS may guide further studies into the role of TCS in GBS pathogenicity and biology.

scholarly journals Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: multiple two-component systems involved in acid adaptation

Microbiology ◽  
2009 ◽  
Vol 155 (10) ◽  
pp. 3322-3332 ◽  
Author(s):  
Yongxing Gong ◽  
Xiao-Lin Tian ◽  
Tara Sutherland ◽  
Gary Sisson ◽  
Junni Mai ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Expression Profiles ◽  
Acid Tolerance ◽  
Transcriptional Analysis ◽  
Acidic Ph ◽  
Acid Adaptation ◽  
Component Systems ◽  
Two Component ◽  
Tolerance Response ◽  
Two Component Systems

Streptococcus mutans in dental biofilms is regularly exposed to cycles of acidic pH during the ingestion of fermentable dietary carbohydrates. The ability of S. mutans to tolerate low pH is crucial for its virulence and pathogenesis in dental caries. To better understand its acid tolerance mechanisms, we performed genome-wide transcriptional analysis of S. mutans in response to an acidic pH signal. The preliminary results showed that adaptation of S. mutans to pH 5.5 induced differential expression of nearly 14 % of the genes in the genome, including 169 upregulated genes and 108 downregulated genes, largely categorized into nine functional groups. One of the most interesting findings was that the genes encoding multiple two-component systems (TCSs), including CiaHR, LevSR, LiaSR, ScnKR, Hk/Rr1037/1038 and ComDE, were upregulated during acid adaptation. Real-time qRT-PCR confirmed the same trend in the expression profiles of these genes at pH 5.5. To determine the roles of these transduction systems in acid adaptation, mutants with a deletion of the histidine-kinase-encoding genes were constructed and assayed for the acid tolerance response (ATR). The results revealed that inactivation of each of these systems resulted in a mutant that was impaired in ATR, since pre-exposure of these mutants to pH 5.5 did not induce the same level of protection against lethal pH levels as the parent did. A competitive fitness assay showed that all the mutants were unable to compete with the parent strain for persistence in dual-strain mixed cultures at acidic pH, although, with the exception of the mutant in liaS, little effect was observed at neutral pH. The evidence from this study suggests that the multiple TCSs are required for S. mutans to orchestrate its signal transduction networks for optimal adaptation to acidic pH.

scholarly journals Cross-regulation between RpfG and HtsHs to regulate antibiotic biosynthesis in Lysobacter

2020 ◽  
Author(s):  
Kaihuai Li ◽  
Gaoge Xu ◽  
Bo Wang ◽  
Guichun Wu ◽  
Fengquan Liu
Keyword(s):  
Gene Expression ◽  
Environmental Changes ◽  
Antibiotic Biosynthesis ◽  
Two Component System ◽  
Independent Manner ◽  
Heat Stable ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Sense And Respond

AbstractBacterial two-component systems (TCSs) sense and respond to environmental changes and modulate downstream gene expression. However, the mechanism of cross-talk between multiple TCSs is unclear. In this study, we report a previously uncharacterized mechanism by which the TCS protein RpfG interacts with hybrid two-component system (HyTCS) proteins HtsH1, HtsH2 and HtsH3 to regulate antibiotic biosynthesis in Lysobacter. RpfG, a phosphodiesterase (PDE), can degrade c-di-GMP to 5’-pGpG and can regulate antibiotic heat-stable antifungal factor (HSAF) biosynthesis in a PDE- independent manner. Thus, we wondered whether RpfG regulate HSAF biosynthesis through interactions with other factors. Subsequently, we demonstrated that RpfG interacts with three HyTCS proteins (HtsH1, HtsH2 and HtsH3), that can inhibit the PDE enzymatic activity of RpfG. Importantly, deletion of htsH1, htsH2 and htsH3 resulted in significantly decreased HSAF production, and we showed that HtsH1, HtsH2 and HtsH3 depend on their phosphorylation activity to directly regulate HSAF biosynthesis gene expression. Our results reveal that RpfG does not depend on PDE activity to regulate HSAF biosynthesis, rather it interacts with HtsH1, HtsH2 and HtsH3 to do so, a regulatory mechanism that may be a conserved paradigm in Lysobacter and Xanthomonas.

The role of ARR22 and two-component systems during Arabidopsis pod development

2007 ◽  
Vol 146 (4) ◽  
pp. S270-S271
Author(s):  
E. Naomab ◽  
S. Gattolin ◽  
M. Alandete-Saez ◽  
K. Elliott ◽  
Z. Gonzalez-Carranza ◽  
...  
Keyword(s):  
Component Systems ◽  
Two Component ◽  
Pod Development ◽  
Two Component Systems
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