scholarly journals Salmonella entericaSerovar Typhimurium CpxRA Two-Component System Contributes to Gut Colonization inSalmonella-Induced Colitis

2018 ◽  
Vol 86 (7) ◽  
pp. e00280-18 ◽  
Author(s):  
Mayuka Fujimoto ◽  
Ryosuke Goto ◽  
Takeshi Haneda ◽  
Nobuhiko Okada ◽  
Tsuyoshi Miki
Keyword(s):  
Stress Response ◽  
Growth Media ◽  
Two Component System ◽  
Bacterial Gene ◽  
Component System ◽  
Content Type ◽  
Bacterial Gene Expression ◽  
Gut Colonization ◽  
Envelope Stress ◽  
Two Component

ABSTRACTSalmonella enterica, a common cause of diarrhea, has to colonize the gut lumen to elicit disease. In the gut, the pathogen encounters a vast array of environmental stresses that cause perturbations in the bacterial envelope. The CpxRA two-component system monitors envelope perturbations and responds by altering the bacterial gene expression profile. This allowsSalmonellato survive under such harmful conditions. Therefore, CpxRA activation is likely to contribute toSalmonellagut infection. However, the role of the CpxRA-mediated envelope stress response inSalmonella-induced diarrhea is unclear. Here, we show that CpxRA is dispensable for the induction of colitis byS. entericaserovar Typhimurium, whereas it is required for gut colonization. We prove that CpxRA is expressed during gut infection and that the presence of antimicrobial peptides in growth media activates the expression of CpxRA-regulated genes. In addition, we demonstrate that aS. Typhimurium strain lacking thecpxRAgene is able to cause colitis but is unable to continuously colonize the gut. Finally, we show that CpxRA-dependent gut colonization requires the host gut inflammatory response, while DegP, a CpxRA-regulated protease, is dispensable. Our findings reveal that the CpxRA-mediated envelope stress response plays a crucial role inSalmonellagut infection, suggesting that CpxRA might be a promising therapeutic target for infectious diarrhea.

scholarly journals Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System

2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Rong Gao ◽  
Katherine A. Godfrey ◽  
Mahir A. Sufian ◽  
Ann M. Stock
Keyword(s):  
Stress Response ◽  
Natural Environments ◽  
Bacterial Cells ◽  
Two Component System ◽  
Experimental Conditions ◽  
Component System ◽  
Content Type ◽  
Regulatory Pathways ◽  
Pi Starvation ◽  
Two Component

ABSTRACT Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the “memory” to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that “memory” of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal with such complexity. In this study, we examined the molecular “memory” that is generated by previous exposure to stimulus. Under our experimental conditions, activating effects of autoregulated two-component signaling and inhibitory effects of the stress response counterbalanced the transcriptional output to approach response homeostasis whether or not cells had been preexposed to stimulus. Modeling allows prediction of response behavior in different scenarios and demonstrates both the robustness of the system output and its sensitivity to historical parameters such as timing and levels of exposure to stimuli.

scholarly journals The BceABRS Four-Component System Regulates the Bacitracin-Induced Cell Envelope Stress Response in Streptococcus mutans

2010 ◽  
Vol 54 (9) ◽  
pp. 3895-3906 ◽  
Author(s):  
Jing Ouyang ◽  
Xiao-Lin Tian ◽  
Jennifer Versey ◽  
Alexander Wishart ◽  
Yung-Hua Li
Keyword(s):  
Stress Response ◽  
Streptococcus Mutans ◽  
Transcriptional Control ◽  
Cell Envelope ◽  
Genetic Locus ◽  
Binding Motif ◽  
Two Component System ◽  
Component System ◽  
Envelope Stress ◽  
Two Component

ABSTRACT Streptococcus mutans is known to be resistant to bacitracin, a cyclic polypeptide antibiotic produced by certain species of the genus Bacillus. This property is often exploited in the isolation of S. mutans strains from highly heterogeneous oral microflora. A genetic locus consisting of a four-gene operon, bceABRS (formerly mbrABCD), the component genes of which are homologous to Bacillus subtilis bceRS-bceAB (encoding a two-component system and an ABC transporter), is required for bacitracin resistance in S. mutans. Here we describe the identification of a DNA binding site for the BceR response regulator and its transcriptional control of the bceABRS operon in response to the presence of bacitracin. We provide evidence indicating that phosphorylated BceR binds directly to a conserved invert repeat located between bp −120 and −78 of the bceABRS promoter region and positively regulates expression of the bceABRS operon. We also demonstrate that sensing of bacitracin by the BceS histidine kinase requires the presence of an intact BceAB transporter, since deletion of either bceA or bceB abolishes BceRS-mediated bacitracin sensing. The results suggest that the BceAB transporter acts as a cosensor, together with the BceRS two-component system, for bacitracin perception in S. mutans. By searching the S. mutans genome databases, we have identified three additional genes that share the consensus BceR binding motif at their promoter regions. Our initial work has confirmed that expression of these genes is directly controlled by BceRS, indicating that the bceABRS operon, along with the three additional genes, forms the BceRS regulon in S. mutans. Taking these findings together, we conclude that BceABRS comprises a four-component system that plays an important role in stimulus sensing, signal transduction, the gene regulatory network, and substrate transport for the cell envelope stress response in S. mutans.

scholarly journals Dual Regulation of Phosphatidylserine Decarboxylase Expression by Envelope Stress Responses

2021 ◽  
Vol 8 ◽  
Author(s):  
Yasmine Hassoun ◽  
Julia Bartoli ◽  
Astrid Wahl ◽  
Julie Pamela Viala ◽  
Emmanuelle Bouveret
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Response Regulators ◽  
Two Component System ◽  
Component System ◽  
Basal Expression ◽  
Gene Coding ◽  
Envelope Stress ◽  
Two Component ◽  
Artificial Activation

Bacteria adapt to versatile environments by modulating gene expression through a set of stress response regulators, alternative Sigma factors, or two-component systems. Among the central processes that must be finely tuned is membrane homeostasis, including synthesis of phospholipids (PL). However, few genetic regulations of this process have been reported. We have previously shown that the gene coding the first step of PL synthesis is regulated by σE and ppGpp, and that the BasRS (PmrAB) two component system controls the expression of the DgkA PL recycling enzyme. The gene coding for phosphatidylserine decarboxylase, the last step in phosphatidylethanolamine synthesis is another gene in the PL synthesis pathway susceptible of stress response regulation. Indeed, psd appears in transcriptome studies of the σE envelope stress Sigma factor and of the CpxAR two component system. Interestingly, this gene is presumably in operon with mscM coding for a miniconductance mechanosensitive channel. In this study, we dissected the promoter region of the psd-mscM operon and studied its regulation by σE and CpxR. By artificial activation of σE and CpxRA stress response pathways, using GFP transcriptional fusion and western-blot analysis of Psd and MscM enzyme production, we showed that the operon is under the control of two distinct promoters. One is activated by σE, the second is activated by CpxRA and also responsible for basal expression of the operon. The fact that the phosphatidylethanolamine synthesis pathway is controlled by envelope stress responses at both its first and last steps might be important for adaptation of the membrane to envelope perturbations.

scholarly journals Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System

2016 ◽  
Vol 60 (6) ◽  
pp. 3509-3518 ◽  
Author(s):  
Keith Poole ◽  
Christie Gilmour ◽  
Maya A. Farha ◽  
Erin Mullen ◽  
Calvin Ho-Fung Lau ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Rna Polymerase ◽  
Multidrug Efflux ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Envelope Stress ◽  
Two Component ◽  
Polymerase Inhibitor ◽  
Multidrug Efflux System

A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5-linked aminoglycoside (AG), against wild-typePseudomonas aeruginosaidentified the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5-linked AGs, such as neomycin and ribostamycin, but not the clinically important 4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant lacking the AmgRS envelope stress response two-component system (TCS), which protects the organism from AG-generated membrane-damaging aberrant polypeptides and, thus, promotes AG resistance, an indication that RIF was acting via this TCS in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF-resistant RNA polymerase mutant, consistent with its potentiation of AG activity being dependent on RNA polymerase perturbation. PAR-inducible expression of the AmgRS-dependent geneshtpXandyccAwas reduced by RIF, suggesting that AG activation of this TCS was compromised by this agent. Still, RIF did not compromise the membrane-protective activity of AmgRS, an indication that it impacted some other function of this TCS. RIF potentiated the activities of 4,5-linked AGs against several AG-resistant clinical isolates, in two cases also potentiating the activity of the 4,6-linked AGs. These cases were, in one instance, explained by an observed AmgRS-dependent expression of the MexXY multidrug efflux system, which accommodates a range of AGs, with RIF targeting of AmgRS underminingmexXYexpression and its promotion of resistance to 4,5- and 4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG resistance inP. aeruginosa, RIF might be a useful adjuvant in the AG treatment ofP. aeruginosainfections.

scholarly journals Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Kevin D. Mlynek ◽  
William E. Sause ◽  
Derek E. Moormeier ◽  
Marat R. Sadykov ◽  
Kurt R. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factors ◽  
Virulence Gene ◽  
Nutrient Depletion ◽  
Global Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

Global chromosome topology and the two-component systems in concerted manner regulate transcription in Streptomyces

2021 ◽  
Author(s):  
Martyna Gongerowska-Jac ◽  
Marcin Jan Szafran ◽  
Jakub Mikołajczyk ◽  
Justyna Szymczak ◽  
Magdalena Bartyńska ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Dna Supercoiling ◽  
Complex Life Cycle ◽  
Two Component System ◽  
Bacterial Gene ◽  
Component System ◽  
Global Regulators ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

Bacterial gene expression is controlled at multiple levels, with chromosome supercoiling being one of the most global regulators. Global DNA supercoiling is maintained by the orchestrated action of topoisomerases. In Streptomyces, mycelial soil bacteria with a complex life cycle, topoisomerase I depletion led to elevated chromosome supercoiling, changed expression of significant fraction of genes, delayed growth and blocked sporulation. To identify supercoiling-induced sporulation regulators, we searched for S. coelicolor transposon mutants that were able to restore sporulation despite high chromosome supercoiling. We established that transposon insertion in genes encoding a novel two-component system named SatKR reversed the sporulation blockage resulting from topoisomerase I depletion. Transposition in satKR abolished the transcriptional induction of the genes within the so-called supercoiling-hypersensitive cluster (SHC). Moreover, we found that activated SatR also induced the same set of SHC genes under normal supercoiling conditions. We determined that the expression of genes in this region impacted S. coelicolor growth and sporulation. Interestingly, among the associated products is another two-component system (SitKR), indicating the potential for cascading regulatory effects driven by the SatKR and SitKR two-component systems. Thus, we demonstrated the concerted activity of chromosome supercoiling and a hierarchical two-component signalling system that impacts gene activity governing Streptomyces growth and sporulation.

scholarly journals The Staphylococcus aureus KdpDE Two-Component System Couples Extracellular K+Sensing and Agr Signaling to Infection Programming

2011 ◽  
Vol 79 (6) ◽  
pp. 2154-2167 ◽  
Author(s):  
Ting Xue ◽  
Yibo You ◽  
De Hong ◽  
Haipeng Sun ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Uptake System ◽  
Main Function ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Virulence Regulator ◽  
External K

ABSTRACTThe Kdp system is widely distributed among bacteria. InEscherichia coli, the Kdp-ATPase is a high-affinity K+uptake system and its expression is activated by the KdpDE two-component system in response to K+limitation or salt stress. However, information about the role of this system in many bacteria still remains obscure. Here we demonstrate that KdpFABC inStaphylococcus aureusis not a major K+transporter and that the main function of KdpDE is not associated with K+transport but that instead it regulates transcription for a series of virulence factors through sensing external K+concentrations, indicating that this bacterium might modulate its infectious status through sensing specific external K+stimuli in different environments. Our results further reveal thatS. aureusKdpDE is upregulated by the Agr/RNAIII system, which suggests that KdpDE may be an important virulence regulator coordinating the external K+sensing and Agr signaling during pathogenesis in this bacterium.

scholarly journals The CasKR Two-Component System Is Required for the Growth of Mesophilic and Psychrotolerant Bacillus cereus Strains at Low Temperatures

2014 ◽  
Vol 80 (8) ◽  
pp. 2493-2503 ◽  
Author(s):  
Sara Esther Diomandé ◽  
Stéphanie Chamot ◽  
Vera Antolinos ◽  
Florian Vasai ◽  
Marie-Hélène Guinebretière ◽  
...  
Keyword(s):  
Bacillus Cereus ◽  
Food Poisoning ◽  
Two Component System ◽  
Diverse Range ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Temperature Ranges ◽  
Different Strains

ABSTRACTThe different strains ofBacillus cereuscan grow at temperatures covering a very diverse range. SomeB. cereusstrains can grow in chilled food and consequently cause food poisoning. We have identified a new sensor/regulator mechanism involved in low-temperatureB. cereusgrowth. Construction of a mutant of this two-component system enabled us to show that this system, called CasKR, is required for growth at the minimal temperature (Tmin). CasKR was also involved in optimal cold growth aboveTminand in cell survival belowTmin. Microscopic observation showed that CasKR plays a key role in cell shape during cold growth. Introducing thecasKRgenes in a ΔcasKRmutant restored its ability to grow atTmin. Although it was first identified in the ATCC 14579 model strain, this mechanism has been conserved in most strains of theB. cereusgroup. We show that the role of CasKR in cold growth is similar in otherB. cereus sensu latostrains with different growth temperature ranges, including psychrotolerant strains.

scholarly journals Identification of a Second Two-Component Signal Transduction System That Controls Fosfomycin Tolerance and Glycerol-3-Phosphate Uptake

2014 ◽  
Vol 197 (5) ◽  
pp. 861-871 ◽  
Author(s):  
Kumiko Kurabayashi ◽  
Yuko Hirakawa ◽  
Koichi Tanimoto ◽  
Haruyoshi Tomita ◽  
Hidetada Hirakawa
Keyword(s):  
Phosphate Uptake ◽  
Response Regulator ◽  
Anaerobic Respiration ◽  
Regulatory System ◽  
Carbon Substrate ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Biological Cost

Particular interest in fosfomycin has resurfaced because it is a highly beneficial antibiotic for the treatment of refractory infectious diseases caused by pathogens that are resistant to other commonly used antibiotics. The biological cost to cells of resistance to fosfomycin because of chromosomal mutation is high. We previously found that a bacterial two-component system, CpxAR, induces fosfomycin tolerance in enterohemorrhagicEscherichia coli(EHEC) O157:H7. This mechanism does not rely on irreversible genetic modification and allows EHEC to relieve the fitness burden that results from fosfomycin resistance in the absence of fosfomycin. Here we show that another two-component system, TorSRT, which was originally characterized as a regulatory system for anaerobic respiration utilizing trimethylamine-N-oxide (TMAO), also induces fosfomycin tolerance. Activation of the Tor regulatory pathway by overexpression oftorR, which encodes the response regulator, or addition of TMAO increased fosfomycin tolerance in EHEC. We also show that phosphorylated TorR directly represses the expression ofglpT, a gene that encodes a symporter of fosfomycin and glycerol-3-phosphate, and activation of the TorR protein results in the reduced uptake of fosfomycin by cells. However, cells in which the Tor pathway was activated had an impaired growth phenotype when cultured with glycerol-3-phosphate as a carbon substrate. These observations suggest that the TorSRT pathway is the second two-component system to reversibly control fosfomycin tolerance and glycerol-3-phosphate uptake in EHEC, and this may be beneficial for bacteria by alleviating the biological cost. We expect that this mechanism could be a potential target to enhance the utility of fosfomycin as chemotherapy against multidrug-resistant pathogens.

scholarly journals The pneumococcal two-component system VisRH is linked to enhanced intracellular survival of Streptococcus pneumoniae in influenza-infected pneumocytes

2019 ◽  
Author(s):  
Nicolás M. Reinoso-Vizcaíno ◽  
Melina B. Cian ◽  
Paulo R. Cortes ◽  
Nadia B. Olivero ◽  
Mirelys Hernandez-Morfa ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Stress Response ◽  
Influenza A Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Intracellular Survival ◽  
Bacterial Pathogenesis ◽  
Two Component System ◽  
Component System ◽  
Two Component

AbstractThe virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system VisRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔvisR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔvisR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the VisRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.Author summaryS. pneumoniae is an inhabitant of the human nasopharynx that is capable of causing a variety of infections contributing to an estimated 1.6 million deaths each year. Many of these deaths occur as result of secondary S. pneumoniae infections following seasonal or pandemic influenza. Although S. pneumoniae is considered a typical extracellular pathogen, an intracellular survival mechanism has been more recently recognized as significant in bacterial pathogenesis. The synergistic effects between influenza A and S. pneumoniae in secondary bacterial infection are well documented; however, the effects of influenza infections on intracellular survival of S. pneumoniae are ill-defined. Here, we provide evidence that influenza infection increases S. pneumoniae intracellular survival in pneumocytes. We demonstrate that the poorly understood VisRH signal transduction system in pneumococcus controls the expression of genes involved in the stress response that S. pneumoniae needs to increase intracellular survival in influenza A-infected pneumocytes. These findings have important implications for understanding secondary bacterial pathogenesis following influenza and for the treatment of such infections in influenza-stricken patients.

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