scholarly journals Two Spx Proteins Modulate Stress Tolerance, Survival, and Virulence in Streptococcus mutans

2010 ◽  
Vol 192 (10) ◽  
pp. 2546-2556 ◽  
Author(s):  
Jessica K. Kajfasz ◽  
Isamar Rivera-Ramos ◽  
Jacqueline Abranches ◽  
Alaina R. Martinez ◽  
Pedro L. Rosalen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Streptococcus Mutans ◽  
Gram Positive ◽  
Enzymatic Assays ◽  
Stress Genes ◽  
Gram Positive Bacteria ◽  
Underlying Mechanisms ◽  
Controlling Processes ◽  
High Degree

ABSTRACT Previous work suggested that the underlying mechanisms by which the Streptococcus mutans ClpXP protease affects virulence traits are associated with accumulation of two orthologues of the Spx regulator, named SpxA and SpxB. Here, a thorough characterization of strains lacking the spx genes (ΔspxA, ΔspxB, and ΔspxA ΔspxB) revealed that Spx, indeed, participates in the regulation of processes associated with S. mutans pathogenesis. The ΔspxA strain displayed impaired ability to grow under acidic and oxidative stress conditions and had diminished long-term viability at low pH. Although the ΔspxB strain did not show any inherent stress-sensitive phenotype, the phenotypes observed in ΔspxA were more pronounced in the ΔspxA ΔspxB double mutant. By using two in vivo models, we demonstrate for the first time that Spx is required for virulence in a Gram-positive pathogen. Microarrays confirmed the global regulatory role of SpxA and SpxB. In particular, SpxA was shown to positively regulate genes associated with oxidative stress, a finding supported by enzymatic assays. SpxB had a secondary role in regulation of oxidative stress genes but appeared to play a larger role in controlling processes associated with cell wall homeostasis. Given the high degree of conservation between Spx proteins of low-GC Gram-positive bacteria, these results are likely to have broad implications.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

scholarly journals In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
The Other ◽  
Vitro Activity ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

PTS 50: Past, Present and Future, or Diauxie Revisited

2015 ◽  
Vol 25 (2-3) ◽  
pp. 79-93 ◽  
Author(s):  
Joseph W. Lengeler
Keyword(s):  
Catabolite Repression ◽  
Biological Significance ◽  
Cellular Growth ◽  
Gram Positive ◽  
Gram Negative ◽  
Inducer Exclusion ◽  
Gram Positive Bacteria ◽  
Cellular Control

<b><i>Past:</i></b> The title ‘PTS 50 or The PTS after 50 years' relies on the first description in 1964 of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) by Kundig, Gosh and Roseman [Proc Natl Acad Sci USA 1964;52:1067-1074]. The system comprised proteins named Enzyme I, HPr and Enzymes II, as part of a novel PTS for carbohydrates in Gram-negative and Gram-positive bacteria, whose ‘biological significance remained unclear'. In contrast, studies which would eventually lead to the discovery of the central role of the PTS in bacterial metabolism had been published since before 1942. They are primarily linked to names like Epps and Gale, J. Monod, Cohn and Horibata, and B. Magasanik, and to phenomena like ‘glucose effects', ‘diauxie', ‘catabolite repression' and carbohydrate transport. <b><i>Present:</i></b> The pioneering work from Roseman's group initiated a flood of publications. The extraordinary progress from 1964 to this day in the qualitative and in vitro description of the genes and enzymes of the PTS, and of its multiple roles in global cellular control through ‘inducer exclusion', gene induction and ‘catabolite repression', in cellular growth, in cell differentiation and in chemotaxis, as well as the differences of its functions between Gram-positive and Gram-negative bacteria, was one theme of the meeting and will not be treated in detail here. <b><i>Future:</i></b> At the 1988 Paris meeting entitled ‘The PTS after 25 years', Saul Roseman predicted that ‘we must describe these interactions [of the PTS components] in a quantitative way [under] in vivo conditions'. I will present some results obtained by our group during recent years on the old phenomenon of diauxie by means of very fast and quantitative tests, measured in vivo, and obtained from cultures of isogenic mutant strains growing under chemostat conditions. The results begin to hint at the problems relating to future PTS research, but also to the ‘true science' of Roseman.

scholarly journals Bitter Taste Receptor T2R14 Modulates Gram-Positive Bacterial Internalization and Survival in Gingival Epithelial Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 9920
Author(s):  
Manoj Reddy Medapati ◽  
Anjali Yadav Bhagirath ◽  
Nisha Singh ◽  
Robert J. Schroth ◽  
Rajinder P. Bhullar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Gram Positive ◽  
Direct Role ◽  
Gram Positive Bacteria ◽  
Inhibition Of Growth ◽  
Gingival Epithelial Cells ◽  
Underlying Mechanisms

Bitter-taste receptors (T2Rs) have emerged as key players in host–pathogen interactions and important modulators of oral innate immunity. Previously, we reported that T2R14 is expressed in gingival epithelial cells (GECs) and interacts with competence stimulating peptides (CSPs) secreted by the cariogenic Streptococcus mutans. The underlying mechanisms of the innate immune responses and physiological effects of T2R14 on Gram-positive bacteria are not well characterized. In this study, we examined the role of T2R14 in internalization and growth inhibitory effects on Gram-positive bacteria, namely Staphylococcus aureus and S. mutans. We utilized CRISPR-Cas9 T2R14 knockdown (KD) GECs as the study model to address these key physiological mechanisms. Our data reveal that the internalization of S. aureus is significantly decreased, while the internalization of S. mutans remains unaffected upon knockdown of T2R14 in GECs. Surprisingly, GECs primed with S. mutans CSP-1 resulted in an inhibition of growth for S. aureus, but not for S. mutans. The GECs infected with S. aureus induced T2R14-dependent human β-defensin-2 (hBD-2) secretion; however, S. mutans–infected GECs did not induce hBD-2 secretion, but induced T2R14 dependent IL-8 secretion. Interestingly, our results show that T2R14 KD affects the cytoskeletal reorganization in GECs, thereby inhibiting S. aureus internalization. Our study highlights the distinct mechanisms and a direct role of T2R14 in influencing physiological responses to Gram-positive bacteria in the oral cavity.

Zinc oxide microrods and nanorods: different antibacterial activity and their mode of action against Gram-positive bacteria

RSC Advances ◽  
2014 ◽  
Vol 4 (99) ◽  
pp. 56031-56040 ◽  
Author(s):  
Ilaria Rago ◽  
Chandrakanth Reddy Chandraiahgari ◽  
Maria P. Bracciale ◽  
Giovanni De Bellis ◽  
Elena Zanni ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Antibacterial Activity ◽  
Mode Of Action ◽  
Gram Positive ◽  
Gram Positive Bacteria

ZnO micro and nanorods, produced through simple and inexpensive techniques, resulted to be strong antimicrobials against Gram-positive bacteria, in vitro as well as in vivo, by altering cell outer structures like membrane and exopolysaccharides.

scholarly journals ppGpp negatively impacts ribosome assembly affecting growth and antimicrobial tolerance in Gram-positive bacteria

2016 ◽  
Vol 113 (12) ◽  
pp. E1710-E1719 ◽  
Author(s):  
Rebecca M. Corrigan ◽  
Lauren E. Bellows ◽  
Alison Wood ◽  
Angelika Gründling
Keyword(s):  
Stringent Response ◽  
Ribosome Assembly ◽  
Bacterial Survival ◽  
Positive Bacterium ◽  
Gram Positive ◽  
Guanosine Tetraphosphate ◽  
Target Proteins ◽  
Gram Positive Bacteria ◽  
Ribosome Inactivation

The stringent response is a survival mechanism used by bacteria to deal with stress. It is coordinated by the nucleotides guanosine tetraphosphate and pentaphosphate [(p)ppGpp], which interact with target proteins to promote bacterial survival. Although this response has been well characterized in proteobacteria, very little is known about the effectors of this signaling system in Gram-positive species. Here, we report on the identification of seven target proteins for the stringent response nucleotides in the Gram-positive bacteriumStaphylococcus aureus. We demonstrate that the GTP synthesis enzymes HprT and Gmk bind with a high affinity, leading to an inhibition of GTP production. In addition, we identified five putative GTPases—RsgA, RbgA, Era, HflX, and ObgE—as (p)ppGpp target proteins. We show that RsgA, RbgA, Era, and HflX are functional GTPases and that their activity is promoted in the presence of ribosomes but strongly inhibited by the stringent response nucleotides. By characterizing the function of RsgA in vivo, we ascertain that this protein is involved in ribosome assembly, with anrsgAdeletion strain, or a strain inactivated for GTPase activity, displaying decreased growth, a decrease in the amount of mature 70S ribosomes, and an increased level of tolerance to antimicrobials. We additionally demonstrate that the interaction of ppGpp with cellular GTPases is not unique to the staphylococci, as homologs fromBacillus subtilisandEnterococcus faecalisretain this ability. Taken together, this study reveals ribosome inactivation as a previously unidentified mechanism through which the stringent response functions in Gram-positive bacteria.

Daptomycin and AgNP co-loaded rGO nanocomposites for specific treatment of Gram-positive bacterial infection in vitro and in vivo

2019 ◽  
Vol 7 (12) ◽  
pp. 5097-5111 ◽  
Author(s):  
Chunyi Tong ◽  
Li Li ◽  
Feng Xiao ◽  
Jialong Fan ◽  
Xianghua Zhong ◽  
...  
Keyword(s):  
Wound Healing ◽  
Bacterial Infection ◽  
Specific Treatment ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Bacteria Killing

rGO was used for simultaneously anchoring AgNPs and Daptomycin to prepare rGO@Ag@Dap for anti-bacterium. The new nanomaterial showed strong Gram-positive bacteria killing ability in vitro and enhanced wound healing infected with S. aureus in vivo.

scholarly journals Mutations of the Listeria monocytogenes PeptidoglycanN-Deacetylase andO-Acetylase Result in Enhanced Lysozyme Sensitivity, Bacteriolysis, and Hyperinduction of Innate Immune Pathways

2011 ◽  
Vol 79 (9) ◽  
pp. 3596-3606 ◽  
Author(s):  
Chris S. Rae ◽  
Aimee Geissler ◽  
Paul C. Adamson ◽  
Daniel A. Portnoy
Keyword(s):  
Listeria Monocytogenes ◽  
Transcriptional Responses ◽  
Gram Positive ◽  
Content Type ◽  
Growth Defects ◽  
Gram Positive Bacteria ◽  
Host Cell Death

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd−, Oat−, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd−and Pgd−Oat−double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM−macrophages. The addition of extracellular lysozyme to LysM−macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.

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