Plausible role of bacterial toxin–antitoxin system in persister cell formation and elimination

2019 ◽  
Vol 34 (3) ◽  
pp. 97-107 ◽  
Author(s):  
Prajita Paul ◽  
Bikash R. Sahu ◽  
Mrutyunjay Suar
Keyword(s):  
Cell Formation ◽  
Bacterial Toxin ◽  
Persister Cell

scholarly journals Role of Global Regulators and Nucleotide Metabolism in Antibiotic Tolerance in Escherichia coli

2008 ◽  
Vol 52 (8) ◽  
pp. 2718-2726 ◽  
Author(s):  
Sonja Hansen ◽  
Kim Lewis ◽  
Marin Vulić
Keyword(s):  
Escherichia Coli ◽  
Cell Formation ◽  
Nucleotide Metabolism ◽  
Flavin Mononucleotide ◽  
Formation Mechanisms ◽  
Antibiotic Tolerance ◽  
Persister Cells ◽  
Global Regulators ◽  
Persister Cell

ABSTRACT Bacterial populations produce a small number of persister cells that exhibit multidrug tolerance. Persister cells are largely responsible for the antibiotic recalcitrance of biofilm infections. The mechanism of persister cell formation largely remains unknown due to the challenges in identifying persister genes. We screened an ordered comprehensive library of 3,985 Escherichia coli knockout strains to identify mutants with altered antibiotic tolerance. Stationary-state cultures in 96-well plates were exposed to ofloxacin at a concentration which allows only tolerant persister cells to survive. The persister cell level of each culture was determined. A total of 150 mutants with decreased persistence were identified in the initial screen, and subsequent validation confirmed that neither the growth rate nor the ofloxacin MIC was affected for 10 of them. The genes affected in these strains were dnaJ and dnaK (chaperones), apaH (diadenosine tetraphosphatase), surA (peptidyl-prolyl cis-trans isomerase), fis and hns (global regulators), hnr (response regulator of RpoS), dksA (transcriptional regulator of rRNA transcription), ygfA (5-formyl-tetrahydrofolate cyclo-ligase), and yigB (flavin mononucleotide [FMN] phosphatase). The prominent presence of global regulators among these strains pointed to the likely redundancy of persister cell formation mechanisms: the elimination of a regulator controlling several redundant persister genes would be expected to produce a phenotype. This observation is consistent with previous findings for a possible role of redundant genes such as toxin/antitoxin modules in persister cell formation. ygfA and yigB were of special interest. The mammalian homolog of YgfA (methenyltetrahydrofolate synthetase) catalyzes the conversion of 5-formyl-tetrahydrofolate (THF) into the rapidly degraded 5,10-methenyl-THF, depleting the folate pool. The YigB protein is a phosphatase of FMN which would deplete the pool of this cofactor. Stochastic overexpression of these genes could lead to dormancy and, hence, tolerance by depleting the folate and FMN pools, respectively. Consistent with this scenario, the overexpression of both genes produced increased tolerance to ofloxacin.

The role of ATP pools in persister cell formation in (fluoro)quinolone-susceptible and -resistant strains of Salmonella enterica ser. Typhimurium

2017 ◽  
Vol 210 ◽  
pp. 116-123 ◽  
Author(s):  
Sebastian Braetz ◽  
Peter Schwerk ◽  
Arthur Thompson ◽  
Karsten Tedin ◽  
Marcus Fulde
Keyword(s):  
Salmonella Enterica ◽  
Cell Formation ◽  
Resistant Strains ◽  
Persister Cell

Reviewing the role of peptide rarity in bacterial toxin immunomics

10.2741/s263 ◽  
2012 ◽  
Vol S4 (1) ◽  
pp. 216-225 ◽  
Author(s):  
Darja Kanduc
Keyword(s):  
Bacterial Toxin

Beyond Promoter: The Role of Macrophage in Invasion and Progression of Renal Cell Carcinoma

2020 ◽  
Vol 15 (7) ◽  
pp. 588-596
Author(s):  
Haibao Zhang ◽  
Guodong Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Formation ◽  
Biological Behavior ◽  
Tumor Stem Cell ◽  
The Past ◽  
The Common

Renal cell carcinoma (RCC) is one of the common urologic neoplasms, and its incidence has been increasing over the past several decades; however, its pathogenesis is still unknown up to now. Recent studies have found that in addition to tumor cells, other cells in the tumor microenvironment also affect the biological behavior of the tumor. Among them, macrophages exist in a large amount in tumor microenvironment, and they are generally considered to play a key role in promoting tumorigenesis. Therefore, we summarized the recent researches on macrophage in the invasiveness and progression of RCC in latest years, and we also introduced and discussed many studies about macrophage in RCC to promote angiogenesis by changing tumor microenvironment and inhibit immune response in order to activate tumor progression. Moreover, macrophage interactes with various cytokines to promote tumor proliferation, invasion and metastasis, and it also promotes tumor stem cell formation and induces drug resistance in the progression of RCC. The highlight of this review is to make a summary of the roles of macrophage in the invasion and progression of RCC; at the same time to raise some potential and possible targets for future RCC therapy.

Dynamic Role of Macrophage Sub Types for Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy

2020 ◽  
Vol 18 ◽  
Author(s):  
Parimalanandhini Duraisamy ◽  
Sangeetha Ravi ◽  
Mahalakshmi Krishnan ◽  
Catherene M. Livya ◽  
Beulaja Manikandan ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Atherosclerosis Progression ◽  
Proinflammatory Mediators ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Inflammatory Site

: Atherosclerosis, a major contributor to cardiovascular disease is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes recruitment of monocytes to the inflammatory sites and subside pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 has to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of proinflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage has atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.

scholarly journals Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

2021 ◽  
Vol 22 (5) ◽  
pp. 2529
Author(s):  
Amin Javadifar ◽  
Sahar Rastgoo ◽  
Maciej Banach ◽  
Tannaz Jamialahmadi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Special Focus ◽  
Lipid Uptake ◽  
Therapeutic Goals ◽  
Expression Of Genes

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.

RNA antitoxin SprF1 binds ribosomes to attenuate translation and promote persister cell formation in Staphylococcus aureus

2021 ◽  
Author(s):  
Marie-Laure Pinel-Marie ◽  
Régine Brielle ◽  
Camille Riffaud ◽  
Noëlla Germain-Amiot ◽  
Norbert Polacek ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Formation ◽  
Persister Cell

Abstract 3691: Deletion of Suppressor Of Cytokine Signaling-1 in a Murine Model of Atherosclerosis Results in a Lethal Systemic Inflammation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christina Grothusen ◽  
Harald Schuett ◽  
Stefan Lumpe ◽  
Andre Bleich ◽  
Silke Glage ◽  
...  
Keyword(s):  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
The Impact

Introduction: Atherosclerosis is a chronic inflammatory disease of the cardiovascular system which may result in myocardial infarction and sudden cardiac death. While the role of pro-inflammatory signaling pathways in atherogenesis has been well characterized, the impact of their negative regulators, e.g. suppressor of cytokine signaling (SOCS)-1 remains to be elucidated. Deficiency of SOCS-1 leads to death 3 weeks post-partum due to an overwhelming inflammation caused by an uncontrolled signalling of interferon-gamma (IFNγ). This phenotype can be rescued by generating recombination activating gene (rag)-2, SOCS-1 double knock out (KO) mice lacking mature lymphocytes, the major source of IFNγ. Since the role of SOCS-1 during atherogenesis is unknown, we investigated the impact of a systemic SOCS-1 deficiency in the low-density lipoprotein receptor (ldlr) KO model of atherosclerosis. Material and Methods: socs-1 −/− /rag-2 −/− deficient mice were crossed with ldlr-KO animals. Mice were kept under sterile conditions on a normal chow diet. For in-vitro analyses, murine socs-1 −/− macrophages were stimulated with native low density lipoprotein (nLDL) or oxidized (ox)LDL. SOCS-1 expression was determined by quantitative PCR and western blot. Foam cell formation was determined by Oil red O staining. Results: socs-1 −/− /rag-2 −/− /ldlr −/− mice were born according to mendelian law. Tripel-KO mice showed a reduced weight and size, were more sensitive to bacterial infections and died within 120 days (N=17). Histological analyses revealed a systemic, necrotic, inflammation in Tripel-KO mice. All other genotypes developed no phenotype. In-vitro observations revealed that SOCS-1 mRNA and protein is upregulated in response to stimulation with oxLDL but not with nLDL. Foam cell formation of socs-1 −/− macrophages was increased compared to controls. Conclusion: SOCS-1 seemingly controls critical steps of atherogenesis by modulating foam cell formation in response to stimulation with oxLDL. SOCS-1 deficiency in the ldlr-KO mouse leads to a lethal inflammation. These observations suggest a critical role for SOCS-1 in the regulation of early inflammatory responses in atherogenesis.

scholarly journals Inactivation of TCA cycle enhances Staphylococcus aureus persister cell formation in stationary phase

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ying Wang ◽  
Martin Saxtorph Bojer ◽  
Shilpa Elizabeth George ◽  
Zhihao Wang ◽  
Peter Ruhdal Jensen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Cell Formation ◽  
Tca Cycle ◽  
Persister Cell
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