scholarly journals Antibiotic tolerance, persistence, and resistance of the evolved minimal cell, Mycoplasma mycoides JCVI-Syn3B

2020 ◽  
Author(s):  
Tahmina Hossain ◽  
Heather S. Deter ◽  
Nicholas C. Butzin
Keyword(s):  
Molecular Mechanisms ◽  
Regulatory Mechanisms ◽  
Antibiotic Tolerance ◽  
Minimal Cell ◽  
Antibiotic Resistant ◽  
Mycoplasma Mycoides ◽  
Mechanisms Of Persistence ◽  
Suitable System ◽  
Small Subpopulation ◽  
Multiple Antibiotics

AbstractAntibiotic persisters are a small subpopulation of bacteria that tolerate antibiotics due to a physiologically dormant state. As a result, this phenomenon (persistence) is considered a major contributor to the evolution of antibiotic-resistant and relapsing infections. However, the precise molecular mechanisms of persistence are still unclear. To examine the key mechanisms of persistence, we used the synthetically developed minimal cell Mycoplasma mycoides JCVI-Syn3B; the genome contains <500 genes, which are mostly essential. We found that Syn3B evolves expeditiously and rapidly evolves antibiotic resistance to kasugamycin. The minimum cell also tolerates and persists against multiple antibiotics despite lacking many systems related to bacterial persistence (e.g. toxin-antitoxin systems). These results show that this minimal system is a suitable system to unravel the central regulatory mechanisms of persistence.One Sentence SummaryEssential genes are sufficient for antibiotic tolerance and persistence in the minimal cell.

scholarly journals Antibiotic tolerance, persistence, and resistance of the evolved minimal cell, Mycoplasma mycoides JCVI-Syn3B.

iScience ◽  
2021 ◽  
pp. 102391
Author(s):  
Tahmina Hossain ◽  
Heather S. Deter ◽  
Eliza J. Peters ◽  
Nicholas C. Butzin
Keyword(s):  
Antibiotic Tolerance ◽  
Minimal Cell ◽  
Mycoplasma Mycoides

The impact of Traditional Chinese Medicine on mitophagy in disease models

2021 ◽  
Vol 27 ◽  
Author(s):  
Li-Ping Yu ◽  
Ting-Ting Shi ◽  
Yan-Qin Li ◽  
Jian-Kang Mu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Disease Models ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

scholarly journals Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiaochun Xue ◽  
Jianhua Wu ◽  
Junhui Li ◽  
Jianguo Xu ◽  
Haiying Dai ◽  
...  
Keyword(s):  
Network Analysis ◽  
Skin Lesion ◽  
Candidate Genes ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Regulatory Mechanisms ◽  
Epidermal Keratinocytes ◽  
Dependent Manner ◽  
Human Epidermal Keratinocytes ◽  
Ifn Γ

It was previously reported that the expression of CD274 was down-regulated in psoriatic epidermis, leading to immune disorders of psoriasis. However, the regulatory mechanisms of CD274 were rarely elucidated. We aimed to explore the regulatory mechanisms of CD274. Skin samples were collected from 18 patients with psoriasis vulgaris and 9 healthy participants for RNA sequencing. Candidate genes were chosen based on degree and k-core difference of genes in the co-expression network. The relations between candidate genes and CD274 were validated by flow cytometry and real-time PCR in primary human epidermal keratinocytes. The therapeutic effect of indirubin was assessed in an imiquimod-treated mouse model. Interferon-γ (IFN-γ), cyclin-dependent kinase (CDK) 1, Toll-like receptor 3 (TLR3), TLR4 and interleukin (IL)-17A were considered as candidate genes. In primary human epidermal keratinocytes, the level of CD274 was obviously increased under the stimulation of IFN-γ and CDK1 inhibitor (indirubin), independent of TLR4, TLR3 or IL-17A. Indirubin alleviated the severity of psoriatic mice in a CD274-dependent manner. Co-expression network analysis served as an effective method for the exploration of molecular mechanisms. We demonstrated for the first time that CD274 was the regulator of indirubin-mediated effect on mouse psoriasis-like skin lesion based on co-expression network analysis, contributing to the alleviation of mouse psoriasis-like skin lesion.

scholarly journals Distinct Amino Acid Availability-Dependent Regulatory Mechanisms of MepS and MepM Levels in Escherichia coli

2021 ◽  
Vol 12 ◽  
Author(s):  
Yung Jae Kim ◽  
Byoung Jun Choi ◽  
Si Hyoung Park ◽  
Han Byeol Lee ◽  
Ji Eun Son ◽  
...  
Keyword(s):  
Amino Acid ◽  
Minimal Medium ◽  
Molecular Mechanisms ◽  
Aromatic Amino Acids ◽  
Normal Growth ◽  
Regulatory Mechanisms ◽  
Dependent Manner ◽  
Bacterial Physiology ◽  
Protein Levels ◽  
Amino Acid Availability

Peptidoglycan (PG) hydrolases play important roles in various aspects of bacterial physiology, including cytokinesis, PG synthesis, quality control of PG, PG recycling, and antibiotic resistance. However, the regulatory mechanisms of their expression are poorly understood. In this study, we have uncovered novel regulatory mechanisms of the protein levels of the synthetically lethal PG endopeptidases MepS and MepM, which are involved in PG synthesis. A mutant defective for both MepS and MepM was lethal in an amino acid-rich medium, whereas it exhibited almost normal growth in a minimal medium, suggesting the expendability of MepS and MepM in a minimal medium. Protein levels of MepS and MepM dramatically decreased in the minimal medium. Although MepM was revealed as a substrate of Prc, a periplasmic protease involved in the proteolysis of MepS, only the decrease in the MepS level in the minimal medium was affected by the prc depletion. Phenotypic and biochemical analyses showed that the presence of aromatic amino acids in the medium induced the accumulation of MepS, but not MepM, while the presence of glutamate increased the level of MepM, but not MepS. Together, these results demonstrate that the protein levels of the two major PG endopeptidases are regulated in an amino acid availability-dependent manner, but their molecular mechanisms and signaling are significantly distinct.

scholarly journals Identification of Key Proteins Involved in Axon Guidance Related Disorders: A Systems Biology Approach

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Systems Biology ◽  
Axon Guidance ◽  
Molecular Mechanisms ◽  
Regulatory Mechanisms ◽  
Ppi Network ◽  
Retraction Syndrome ◽  
Horizontal Gaze ◽  
Duane Retraction Syndrome ◽  
Type 3 ◽  
Congenital Fibrosis

Axon guidance is a crucial process for growth of the central and peripheral nervous systems. In this study, 3 axon guidance related disorders, namely- Duane Retraction Syndrome (DRS) , Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) and Congenital fibrosis of the extraocular muscles type 3 (CFEOM3) were studied using various Systems Biology tools to identify the genes and proteins involved with them to get a better idea about the underlying molecular mechanisms including the regulatory mechanisms. Based on the analyses carried out, 7 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with DRS, HGPPS and CFEOM3 associated genes. From the PPI network, 3 have been identified as hub proteins- DRD2, UBC and CUL3.

Regulation of the breast cancer stem cell phenotype by hypoxia-inducible factors

2015 ◽  
Vol 129 (12) ◽  
pp. 1037-1045 ◽  
Author(s):  
Gregg L. Semenza
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Breast Cancer Patients ◽  
Hypoxia Inducible Factors ◽  
Cancer Stem Cell Phenotype ◽  
Response To Chemotherapy ◽  
Small Subpopulation

The small subpopulation of breast cancer cells that possess the capability for self-renewal and formation of secondary tumours that recapitulate the heterogeneity of the primary tumour are referred to as tumour-initiating cells or BCSCs (breast cancer stem cells). The hypoxic tumour microenvironment and chemotherapy actively induce the BCSC phenotype. HIFs (hypoxia-inducible factors) are required and molecular mechanisms by which they promote the BCSC phenotype have recently been delineated. HIF inhibitors block chemotherapy-induced enrichment of BCSCs, suggesting that their use may improve the response to chemotherapy and increase the survival of breast cancer patients.

scholarly journals Unfulfilled Inflammatory Resolution: A Key Factor in the Pathogenesis of Psoriasis

2020 ◽  
Author(s):  
Zohreh Jadali
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Relevant Literature ◽  
Regulatory Mechanisms ◽  
Immune Mediated ◽  
Key Factor ◽  
Inflammation Resolution

Recent literature has highlighted the importance of chronic inflammation in psoriasis pathogenesis. Non-resolving inflammation can trigger progressive tissue damage and inflammatory mediator release which in turn perpetuate the inflammatory cycle. Under normal conditions, inflammatory responses are tightly controlled through several mechanisms that restore normal tissue function and structure. Defects in regulatory mechanisms of the inflammatory response can result in persistent unresolved inflammation and further increases of inflammation. Therefore, this review focuses on defects in regulatory mechanisms of inflammatory responses that lead to uncontrolled chronic inflammation in psoriasis. Databases such as Pubmed Embase, ISI, and Iranian databases including Iranmedex, and SID were researched to identify relevant literature. The results of this review indicate that dysregulation of the inflammatory response may be a likely cause of various immune-mediated inflammatory disorders such as psoriasis. Based on current findings, advances in understanding the cellular and molecular mechanisms involved in inflammation resolution are not only improving our knowledge of the pathogenesis of chronic inflammatory diseases but also supporting the development of new therapeutic strategies.

scholarly journals Draft Genome Sequence of Antibiotic-Resistant Enterococcus faecalis Strain UMB0843, Isolated from the Female Urinary Tract

2020 ◽  
Vol 9 (20) ◽  
Author(s):  
Natalia Purta ◽  
Taylor Miller-Ensminger ◽  
Adelina Voukadinova ◽  
Alan J. Wolfe ◽  
Catherine Putonti
Keyword(s):  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Enterococcus Faecalis ◽  
Genome Analysis ◽  
Nosocomial Infections ◽  
Draft Genome ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Female Urinary Tract ◽  
Multiple Antibiotics

Here, we introduce the 2.8-Mbp draft genome of Enterococcus faecalis strain UMB0843, isolated from the female urinary tract. E. faecalis is a leading cause of nosocomial infections, and many strains are often resistant to multiple antibiotics. We focus our genome analysis on the multiple genes involved in antibiotic resistance in this strain.

scholarly journals The GTEx Consortium atlas of genetic regulatory effects across human tissues

Science ◽  
2020 ◽  
Vol 369 (6509) ◽  
pp. 1318-1330 ◽  
Author(s):  
Keyword(s):  
Complex Traits ◽  
Molecular Mechanisms ◽  
Tissue Expression ◽  
Genetic Effects ◽  
Regulatory Mechanisms ◽  
Human Tissues ◽  
Genetic Associations ◽  
Key Factor ◽  
Regulatory Effects ◽  
Almost All

The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

scholarly journals Slow growth determines nonheritable antibiotic resistance in Salmonella enterica

2019 ◽  
Vol 12 (592) ◽  
pp. eaax3938 ◽  
Author(s):  
Mauricio H. Pontes ◽  
Eduardo A. Groisman
Keyword(s):  
Bacterial Population ◽  
Slow Growth ◽  
Large Fraction ◽  
Signaling Molecules ◽  
Antibiotic Resistant ◽  
Phenotypic Changes ◽  
Resistant Mutants ◽  
Persistent Bacteria ◽  
Small Subpopulation ◽  
Antibiotic Resistant Mutants

Bacteria can withstand killing by bactericidal antibiotics through phenotypic changes mediated by their preexisting genetic repertoire. These changes can be exhibited transiently by a large fraction of the bacterial population, giving rise to tolerance, or displayed by a small subpopulation, giving rise to persistence. Apart from undermining the use of antibiotics, tolerant and persistent bacteria foster the emergence of antibiotic-resistant mutants. Persister formation has been attributed to alterations in the abundance of particular proteins, metabolites, and signaling molecules, including toxin-antitoxin modules, adenosine triphosphate, and guanosine (penta) tetraphosphate, respectively. Here, we report that persistent bacteria form as a result of slow growth alone, despite opposite changes in the abundance of such proteins, metabolites, and signaling molecules. Our findings argue that transitory disturbances to core activities, which are often linked to cell growth, promote a persister state regardless of the underlying physiological process responsible for the change in growth.

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