scholarly journals LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae

Microbiology ◽  
2006 ◽  
Vol 152 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Susana Romao ◽  
Guido Memmi ◽  
Marco R. Oggioni ◽  
Marie-Claude Trombe
Keyword(s):  
Streptococcus Pneumoniae ◽  
Regulatory Networks ◽  
Cell Communication ◽  
Genetic Dissection ◽  
Developmental Physiology ◽  
Adenosyl Methionine ◽  
Sense And Respond ◽  
The One ◽  
The Impact

The ubiquitous protein LuxS with S-ribosylhomocysteinase activity is involved in S-adenosyl methionine detoxification, C-1 unit recycling and the production of autoinducers that allow the cell to sense and respond to cell density. Independent reports describe the impact of LuxS deficiency on Streptococcus pneumoniae virulence in the mouse. In vitro, LuxS deficiency confers discrete phenotypes. A combined approach using genetic dissection and mixed-culture experiments allowed the involvement of LuxS in the developmental physiology of S. pneumoniae to be investigated. Functional LuxS was found to be related on the one hand to down-regulation of competence, and on the other hand to attenuation of autolysis in cultures entering stationary phase. The competence phenotype of luxS mutant bacteria was complemented by media conditioned by competence-defective ComAB0 bacteria, but not by BSA. The autolytic phenotype was complemented by BSA, but not by conditioned supernatants. It is suggested that the impact of LuxS on competence, but not on autolysis, involves cell–cell communication. The phenotype of luxS mutant strains reveals a hierarchy in the competence regulatory networks of S. pneumoniae.

scholarly journals Convergence of Regulatory Networks on the Pilus Locus of Streptococcus pneumoniae

2008 ◽  
Vol 76 (7) ◽  
pp. 3187-3196 ◽  
Author(s):  
Jason W. Rosch ◽  
Beth Mann ◽  
Justin Thornton ◽  
Jack Sublett ◽  
Elaine Tuomanen
Keyword(s):  
Streptococcus Pneumoniae ◽  
Regulatory Networks ◽  
Genetic Recombination ◽  
Lung Epithelial Cells ◽  
Infection Model ◽  
Transcriptional Regulatory Networks ◽  
Transport Response ◽  
The Impact

ABSTRACT The rlrA pilus locus of Streptococcus pneumoniae is an example of a pathogenicity island acquired through genetic recombination. Many acquired genetic elements commandeer preexisting networks of the new organism for transcriptional regulation. We hypothesized that the rlrA locus has integrated into transcriptional regulatory networks controlling expression of virulence factors important in adhesion and invasion. To test this hypothesis, we determined the impact on pilus expression of known regulators controlling adherence, including the two-component systems CbpR/S and HK/RR03 and the transcriptional regulators of divalent cation transporters MerR and PsaR in vitro and in vivo. It was determined that the pilus locus is down-regulated by preexisting networks designed for adhesion and cation transport/response and that its regulation occurs through RlrA. The pilus locus was found to participate in invasion specifically restricted to lung epithelial cells in vitro. While expression of pili had only a small effect on virulence with an intranasal infection model, pili were critically important with an intratracheal infection model. Thus, expression of pili appears to have become integrated into the regulatory circuits for lung-specific invasion by pneumococci.

scholarly journals Synthetic gene regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae

2019 ◽  
Author(s):  
Robin A. Sorg ◽  
Clement Gallay ◽  
Jan-Willem Veening
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Combinatorial Libraries ◽  
Regulatory Elements ◽  
Expression Control ◽  
Gene Expression Control

AbstractStreptococcus pneumoniae can cause disease in various human tissues and organs, including the ear, the brain, the blood and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control in S. pneumoniae. A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND and IMPLY gates. Finally, we demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity of S. pneumoniae.

scholarly journals RegR, a Global LacI/GalR Family Regulator, Modulates Virulence and Competence in Streptococcus pneumoniae

2003 ◽  
Vol 71 (5) ◽  
pp. 2615-2625 ◽  
Author(s):  
Sabine Chapuy-Regaud ◽  
A. David Ogunniyi ◽  
Nicole Diallo ◽  
Yvette Huet ◽  
Jean-François Desnottes ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Nadh Oxidase ◽  
Genetic Dissection ◽  
Loss Of Function ◽  
Global Regulator ◽  
Carbohydrate Utilization ◽  
Rich Media ◽  
Residual Virulence

ABSTRACT The homolactic and catalase-deficient pathogen Streptococcus pneumoniae is not only tolerant to oxygen but requires the activity of its NADH oxidase, Nox, to develop optimal virulence and competence for genetic transformation. In this work, we show that the global regulator RegR is also involved in these traits. Genetic dissection revealed that RegR regulates competence and the expression of virulence factors, including hyaluronidase. In bacteria grown in vitro, RegR represses hyaluronidase. At neutral pH, it increases adherence to A549 epithelial cells, and at alkaline pH, it acts upstream of the CiaRH two-component signaling system to activate competence. These phenotypes are not associated with changes in antibiotic resistance, central metabolism, and carbohydrate utilization. Although the RegR0 (where 0 indicates the loss of the protein) mutation is sufficient to attenuate experimental virulence of strain 23477 in mice, the introduction of an additional hyl0 (where 0 indicates the loss of function) mutation in the RegR0 strain 23302 dramatically reduces its virulence. This indicates that residual virulence of the RegR0 Hyl+ derivative is due to hyaluronidase and supports the dual role of RegR in virulence. This LacI/GalR regulator, not essential for in vitro growth in rich media, is indeed involved in the adaptive response of the pneumococcus via its control of competence, adherence, and virulence.

scholarly journals Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model: Impact of Area under the Curve/MIC Ratios on Eradication

2002 ◽  
Vol 46 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Philip D. Lister
Keyword(s):  
Streptococcus Pneumoniae ◽  
Peak Concentration ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Logarithmic Phase ◽  
Pharmacokinetic Models ◽  
Elimination Half ◽  
The Impact ◽  
Similar Peak

ABSTRACT Previous studies have demonstrated that fluoroquinolone area under the curve (AUC)/MIC ratios of 30 to 50 are sufficient to eradicate pneumococci from in vitro pharmacokinetic models (IVPMs). However, more systematic studies of the impact of AUC/MIC ratios on the antipneumococcal activities of fluoroquinolones are needed. In the present study, a two-compartment IVPM was used to evaluate the impact of AUC/MIC ratios on the pharmacodynamics of gatifloxacin against four strains of Streptococcus pneumoniae. Gatifloxacin MICs were 0.4 to 1 μg/ml, whereas levofloxacin MICs were 1.8 to 3.2 μg/ml. Since both peak concentration/MIC (peak/MIC) and AUC/MIC ratios affect fluoroquinolone pharmacodynamics, logarithmic-phase cultures (5 × 107 CFU/ml) were exposed to gatifloxacin at constant peak/MIC ratios of 2:1 to 3:1 at 0 and 24 h, elimination half-lives were varied to provide a range of AUC/MIC ratios, and changes in viable counts were measured over 30 h. As a comparison, levofloxacin was evaluated at similar peak/MIC ratios and at AUC/MIC ratios of 30 to 38. For each strain, killing rates through 4 to 8 h were similar since peak/MIC ratios were kept constant. However, continued killing and eradication were observed only when gatifloxacin AUC/MIC ratios were 27 to 48. Levofloxacin also provided eradication. In contrast, substantial regrowth was observed in most experiments when gatifloxacin AUC/MIC ratios were 9 to 24. These data provide further support that fluoroquinolone AUC/MIC ratios of approximately 30 or higher can be sufficient for eradication of pneumococci from IVPMs. Furthermore, the overall impact of the AUC/MIC ratio was not influenced by the strain evaluated or its susceptibility to gatifloxacin. Further studies with other fluoroquinolones and pneumococci that exhibit wider ranges of susceptibilities are warranted. In addition, similar studies with higher peak/MIC ratios are needed to better define the impact of AUC/MIC ratios and peak/MIC ratios on the antipneumococcal pharmacodynamics of fluoroquinolones.

scholarly journals Assisted reproductive technologies: psychoneurological, moral-ethical, and socio-cultural aspects

2020 ◽  
Vol 12 (5) ◽  
pp. 104-110
Author(s):  
N. A. Tyuvina ◽  
A. O. Nikolaevskaya
Keyword(s):  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Surrogate Mother ◽  
Reproductive Process ◽  
Vitro Fertilization ◽  
Cultural Traditions ◽  
Cultural Aspects ◽  
The One ◽  
The Impact

The paper provides a definition of sexual and reproductive health and infertility and also reflects modern ideas about ways to overcome infertility using assisted reproductive technologies, such as in vitro fertilization (IVF) and surrogacy. It shows the specificity of the impact of an IVF procedure on the mental health of a potential mother. The features of the neonatal health status, as well as neuropsychiatric disorders in babies born using the IVF procedure are described. The authors present two types of surrogacy (traditional and gestational ones) and the features of their use in different countries according to governmental legislative regulation, socioeconomic and religious factors, and cultural traditions in society. They unveil the features of a psychological relationship between the mother (surrogate and presumed one) and the fetus. The consequences of surrogacy for a surrogate mother, genetic parents, and a child himself/herself are noted to be little studied. It is shown that the development of assisted reproductive technologies (IVF and surrogacy), on the one hand, helps fight infertility and, on the other hand, entails a number of problems (moral and ethical, legal, cultural and religious, socioeconomic, and neuropsychiatric ones) that need to be solved in order to prevent psychological, neurological, and mental abnormalities in all the participants (a surrogate mother, an unborn child, and potential parents) in the assisted reproductive process:

scholarly journals Hemoglobin stimulates vigorous growth of Streptococcus pneumoniae and shapes the pathogen's global transcriptome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fahmina Akhter ◽  
Edroyal Womack ◽  
Jorge E. Vidal ◽  
Yoann Le Breton ◽  
Kevin S. McIver ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Positive Influence ◽  
The Body ◽  
Host Proteins ◽  
Vigorous Growth ◽  
Cultivation In Vitro ◽  
The Impact ◽  
Heme Binding Protein

Abstract Streptococcus pneumoniae (Spn) must acquire iron from the host to establish infection. We examined the impact of hemoglobin, the largest iron reservoir in the body, on pneumococcal physiology. Supplementation with hemoglobin allowed Spn to resume growth in an iron-deplete medium. Pneumococcal growth with hemoglobin was unusually robust, exhibiting a prolonged logarithmic growth, higher biomass, and extended viability in both iron-deplete and standard medium. We observed the hemoglobin-dependent response in multiple serotypes, but not with other host proteins, free iron, or heme. Remarkably, hemoglobin induced a sizable transcriptome remodeling, effecting virulence and metabolism in particular genes facilitating host glycoconjugates use. Accordingly, Spn was more adapted to grow on the human α − 1 acid glycoprotein as a sugar source with hemoglobin. A mutant in the hemoglobin/heme-binding protein Spbhp-37 was impaired for growth on heme and hemoglobin iron. The mutant exhibited reduced growth and iron content when grown in THYB and hemoglobin. In summary, the data show that hemoglobin is highly beneficial for Spn cultivation in vitro and suggest that hemoglobin might drive the pathogen adaptation in vivo. The hemoglobin receptor, Spbhp-37, plays a role in mediating the positive influence of hemoglobin. These novel findings provide intriguing insights into pneumococcal interactions with its obligate human host.

scholarly journals Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1209
Author(s):  
Emma Piattelli ◽  
Johann Peltier ◽  
Olga Soutourina
Keyword(s):  
Signal Transduction ◽  
Regulatory Networks ◽  
Pathogenic Bacteria ◽  
Resistant Bacteria ◽  
Human Pathogens ◽  
Environmental Threats ◽  
Regulatory Rnas ◽  
Sense And Respond ◽  
The Impact ◽  
Signal Transduction Systems

The ability of pathogenic bacteria to stably infect the host depends on their capacity to respond and adapt to the host environment and on the efficiency of their defensive mechanisms. Bacterial envelope provides a physical barrier protecting against environmental threats. It also constitutes an important sensory interface where numerous sensing systems are located. Signal transduction systems include Two-Component Systems (TCSs) and alternative sigma factors. These systems are able to sense and respond to the ever-changing environment inside the host, altering the bacterial transcriptome to mitigate the impact of the stress. The regulatory networks associated with signal transduction systems comprise small regulatory RNAs (sRNAs) that can be directly involved in the expression of virulence factors. The aim of this review is to describe the importance of TCS- and alternative sigma factor-associated sRNAs in human pathogens during infection. The currently available genome-wide approaches for studies of TCS-regulated sRNAs will be discussed. The differences in the signal transduction mediated by TCSs between bacteria and higher eukaryotes and the specificity of regulatory RNAs for their targets make them appealing targets for discovery of new strategies to fight against multi-resistant bacteria.

scholarly journals Myofibroblasts cause heterogeneous Cx43 reduction and are unlikely to be coupled to myocytes in the healing canine infarct

2012 ◽  
Vol 302 (3) ◽  
pp. H790-H800 ◽  
Author(s):  
Jennifer R. Baum ◽  
Biao Long ◽  
Candido Cabo ◽  
Heather S. Duffy
Keyword(s):  
Inflammatory Responses ◽  
Cardiac Fibroblasts ◽  
Cell Communication ◽  
Canine Model ◽  
In Vitro Studies ◽  
Border Zone ◽  
Conduction Abnormalities ◽  
The Impact ◽  
Intact Heart

Following myocardial infarction (MI) inflammatory responses transform cardiac fibroblasts to myofibroblasts, which in vitro studies show form heterocellular gap junctions with cardiac myocytes via Connexin43 (Cx43). The ability to form heterocellular junctions in the intact heart and the impact of these junctions on propagation is unclear. We used a canine model of MI and characterized the distribution and quantity of myofibroblasts in surviving epicardial cells [epicardial border zone (EBZ)]. We found a significant increase in myofibroblasts within the EBZ and no gap junction plaques between myofibroblasts and myocytes. Because myofibroblasts produce IL-1β, which downregulates Cx43, we asked whether myofibroblast proliferation causes loss of Cx43 near myofibroblast clusters. In vitro studies showed that IL-1β caused loss of Cx43 and reduced coupling. Western blot showed a significant increase of IL-1β in the EBZ, and immunohistochemistry showed a loss of Cx43 in regions of myofibroblasts in the intact heart. Additionally, dye studies in intact heart showed no coupling between myocytes and myofibroblasts. To quantify the effect of myofibroblasts on propagation we used a two-dimensional subcellular computer model of the EBZ, which showed that heterogeneities in myofibroblast density lead to conduction abnormalities. In conclusion, an increase of myofibroblasts in the infarcted heart causes heterogeneous Cx43 levels, possibly as a result of the release of IL-1β and decreased cell-cell communication, which leads to conduction abnormalities following MI.

scholarly journals In Vitro Effect of Drilling Speed on the Primary Stability of Narrow Diameter Implants with Varying Thread Designs Placed in Different Qualities of Simulated Bone

Materials ◽  
2019 ◽  
Vol 12 (8) ◽  
pp. 1350
Author(s):  
Georgios E. Romanos ◽  
Daniel J. Bastardi ◽  
Rachel Moore ◽  
Apoorv Kakar ◽  
Yaro Herin ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Primary Stability ◽  
Drilling Speed ◽  
Group A ◽  
The One ◽  
Group B ◽  
Vitro Effect ◽  
The Impact ◽  
Narrow Diameter Implants

It is hypothesized that there is no statistically significant impact of drilling speed (DS) on the primary stability (PS) of narrow-diameter implants (NDIs) with varying thread designs placed in dense and soft simulated bone. The aim of this in vitro study was to evaluate the impact of DS on the PS of NDIs with varying thread designs placed in dense and soft simulated bone. Two hundred and forty osteotomies for placement of various implant macro-designs were divided into three groups (80 implants per group): Group A (NobelActive, 3.0/11.5 mm); Group B (Astra OsseoSpeed-EV, 3.0/11 mm); and Group C (Eztetic-Zimmer, 3.1/11.5 mm) implants. These implants were placed in artificial dense and soft simulated bone using DSs of 800 and 2000 revolutions per minute (RPM). Resonance frequency analysis (RFA) and implant stability quotient (ISQ) were assessed. Group comparisons were performed using the one-way analysis of variance with Tukey’s post hoc tests. Level of significance was set at P < 0.05. In groups A and B, there was no difference in the ISQ for NDIs inserted in dense bone at 800 and 2000 RPM. In Group C, ISQ was significantly higher for NDIs placed in dense bone at 800 PRM compared to 2000 RPM (P < 0.05). In Group A, ISQ values were significantly higher for NDIs inserted in soft bone at 2000 RPM as compared to those inserted at 800 RPM (P < 0.05). For NDIs, a lower drilling speed in dense artificial simulated bone and a higher drilling speed in soft artificial simulated bone is associated with high primary stability.

scholarly journals The Two-Component System 09 of Streptococcus pneumoniae Is Important for Metabolic Fitness and Resistance during Dissemination in the Host

2021 ◽  
Vol 9 (7) ◽  
pp. 1365
Author(s):  
Stephanie Hirschmann ◽  
Alejandro Gómez-Mejia ◽  
Thomas P. Kohler ◽  
Franziska Voß ◽  
Manfred Rohde ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Regulatory System ◽  
Immunoblot Analysis ◽  
Defined Medium ◽  
Host Cells ◽  
Two Component ◽  
Regulatory Effects ◽  
The Impact

The two-component regulatory system 09 of Streptococcus pneumoniae has been shown to modulate resistance against oxidative stress as well as capsule expression. These data and the implication of TCS09 in cell wall integrity have been shown for serotype 2 strain D39. Other data have suggested strain-specific regulatory effects of TCS09. Contradictory data are known on the impact of TCS09 on virulence, but all have been explored using only the rr09-mutant. In this study, we have therefore deleted one or both components of the TCS09 (SP_0661 and SP_0662) in serotype 4 S. pneumoniae TIGR4. In vitro growth assays in chemically defined medium (CDM) using sucrose or lactose as a carbon source indicated a delayed growth of nonencapsulated tcs09-mutants, while encapsulated wild-type TIGR4 and tcs09-mutants have reduced growth in CDM with glucose. Using a set of antigen-specific antibodies, immunoblot analysis showed that only the pilus 1 backbone protein RrgB is significantly reduced in TIGR4ΔcpsΔhk09. Electron microscopy, adherence and phagocytosis assays showed no impact of TCS09 on the TIGR4 cell morphology and interaction with host cells. In contrast, in vivo infections and in particular competitive co-infection experiments demonstrated that TCS09 enhances robustness during dissemination in the host by maintaining bacterial fitness.

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