scholarly journals A Novel Two-Component System Involved in Secretion Stress Response in Streptomyces lividans

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e48987 ◽  
Author(s):  
Sonia Gullón ◽  
Rebeca L. Vicente ◽  
Rafael P. Mellado
2019 ◽  
Author(s):  
Nicolás M. Reinoso-Vizcaíno ◽  
Melina B. Cian ◽  
Paulo R. Cortes ◽  
Nadia B. Olivero ◽  
Mirelys Hernandez-Morfa ◽  
...  

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.


2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Rong Gao ◽  
Katherine A. Godfrey ◽  
Mahir A. Sufian ◽  
Ann M. Stock

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.


2006 ◽  
Vol 188 (2) ◽  
pp. 677-686 ◽  
Author(s):  
Sofiane Ghorbel ◽  
Jan Kormanec ◽  
Alexandra Artus ◽  
Marie-Joelle Virolle

ABSTRACT The PhoR/PhoP two-component system of Streptomyces lividans was previously shown to allow the growth of the bacteria at low Pi concentrations and to negatively control antibiotic production. The present study focuses on the transcriptional analysis of phoR and phoP, along with the phoU and mtpA genes that are transcribed divergently from the phoRP operon in S. lividans. The effect of phoR, phoP, phoU, and ppk mutations on transcription of these genes was examined under phosphate-replete and phosphate-limited conditions. We demonstrated that phoR and phoP were cotranscribed as a leaderless bicistronic transcript cleaved at discrete sites toward the 3′ end of phoR. In addition, phoP could also be transcribed alone from a promoter located at the 3′ end of phoR. The phoU and mtpA genes, predicted to encode metal binding proteins, were shown to be transcribed as monocistronic transcripts. The expression of phoR-phoP, phoP, and phoU was found to be induced under conditions of Pi limitation in S. lividans TK24. This induction, requiring both PhoR and PhoP, was significantly weaker in the phoU mutant but much stronger in the ppk mutant than in the parental strain. The expression of mtpA was also shown to be up-regulated when Pi was limiting but independently of PhoR/PhoP. The induction of mtpA expression was much stronger in the phoU mutant strain than in the other strains. This study revealed interesting regulatory interactions between the different genes and allowed us to propose putative roles for PhoU and MtpA in the adaptation to phosphate scarcity.


2012 ◽  
Vol 194 (7) ◽  
pp. 1800-1814 ◽  
Author(s):  
D. Noone ◽  
E. Botella ◽  
C. Butler ◽  
A. Hansen ◽  
I. Jende ◽  
...  

2010 ◽  
Vol 54 (9) ◽  
pp. 3895-3906 ◽  
Author(s):  
Jing Ouyang ◽  
Xiao-Lin Tian ◽  
Jennifer Versey ◽  
Alexander Wishart ◽  
Yung-Hua Li

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yasmine Hassoun ◽  
Julia Bartoli ◽  
Astrid Wahl ◽  
Julie Pamela Viala ◽  
Emmanuelle Bouveret

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.


2018 ◽  
Vol 86 (7) ◽  
pp. e00280-18 ◽  
Author(s):  
Mayuka Fujimoto ◽  
Ryosuke Goto ◽  
Takeshi Haneda ◽  
Nobuhiko Okada ◽  
Tsuyoshi Miki

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.


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