scholarly journals Unraveling Interactions between the Microbiome and the Host Immune System To Decipher Mechanisms of Disease

mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Catherine A. Lozupone
Keyword(s):  
Immune Modulation ◽  
Inflammatory Responses ◽  
Cell Envelope ◽  
Host Immune System ◽  
Research Focus ◽  
Microbiome Composition ◽  
Graft Versus Host ◽  
Disease Phenotypes ◽  
Mechanistic Insight ◽  
Insight Into

ABSTRACT In recent years, there has been a deluge of papers linking altered microbiome compositions to a myriad of diseases. Mechanistic insight into microbial drivers of disease phenotypes is essential for translation to novel therapies. A key mechanism by which microbes influence health is immune modulation by components of their capsule and cell envelope and their metabolites. A major research focus of my laboratory is to gain mechanistic insight into which microbes modulate host immunity generally and in the context of disease. Using 16S rRNA-targeted sequencing, we have established associations between gut microbiome composition and immune-modulated disease phenotypes in diseases such as graft-versus-host disease in cancer patients undergoing stem cell transplantation. By integrating omics and computational approaches with laboratory experiments, we have expanded knowledge of mechanisms used by host-associated microbes to dampen inflammatory responses. This work has promise for development of novel microbiome-targeted therapeutics.

scholarly journals Structure of bacterial phospholipid transporter MlaFEDB with substrate bound

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nicolas Coudray ◽  
Georgia L Isom ◽  
Mark R MacRae ◽  
Mariyah N Saiduddin ◽  
Gira Bhabha ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Cell Envelope ◽  
Sequence Similarity ◽  
Substrate Recognition ◽  
Membrane Integrity ◽  
Transport Pathway ◽  
Mechanistic Insight ◽  
Membrane Barrier ◽  
Phospholipid Transport ◽  
Insight Into

In double-membraned bacteria, phospholipid transport across the cell envelope is critical to maintain the outer membrane barrier, which plays a key role in virulence and antibiotic resistance. An MCE transport system called Mla has been implicated in phospholipid trafficking and outer membrane integrity, and includes an ABC transporter, MlaFEDB. The transmembrane subunit, MlaE, has minimal sequence similarity to other transporters, and the structure of the entire inner-membrane MlaFEDB complex remains unknown. Here, we report the cryo-EM structure of MlaFEDB at 3.05 Å resolution, revealing distant relationships to the LPS and MacAB transporters, as well as the eukaryotic ABCA/ABCG families. A continuous transport pathway extends from the MlaE substrate-binding site, through the channel of MlaD, and into the periplasm. Unexpectedly, two phospholipids are bound to MlaFEDB, suggesting that multiple lipid substrates may be transported each cycle. Our structure provides mechanistic insight into substrate recognition and transport by MlaFEDB.

Interleukin-17A: A Potential Therapeutic Target in Chronic Lung Diseases

2019 ◽  
Vol 19 (7) ◽  
pp. 921-928 ◽  
Author(s):  
Sadiya Bi Shaikh ◽  
Ashwini Prabhu ◽  
Yashodhar Prabhakar Bhandary
Keyword(s):  
Respiratory Diseases ◽  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Interleukin 17 ◽  
Potential Therapeutic Target ◽  
Chronic Respiratory Diseases ◽  
Chronic Lung Diseases ◽  
Interleukin 17A ◽  
Insight Into

Background: Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has gained a lot of attention because of its involvement in respiratory diseases. Interleukin-17 cytokine family includes six members, out of which, IL-17A participates towards the immune responses in allergy and inflammation. It also modulates the progression of respiratory disorders. Objective: The present review is an insight into the involvement and contributions of the proinflammatory cytokine IL-17A in chronic respiratory diseases like Idiopathic Pulmonary Fibrosis (IPF), Chronic Obstructive Pulmonary Distress (COPD), asthma, pneumonia, obliterative bronchiolitis, lung cancer and many others. Conclusion: IL-17A is a major regulator of inflammatory responses. In all the mentioned diseases, IL- 17A plays a prime role in inducing the diseases, whereas the lack of this pro-inflammatory cytokine reduces the severity of respective respiratory diseases. Thereby, this review suggests IL-17A as an instrumental target in chronic respiratory diseases.

Exploration of Ion Channels in Mycobacterium tuberculosis: Implication on Drug Discovery and Potent Drug Targets Against Tuberculosis

2020 ◽  
Vol 14 (1) ◽  
pp. 14-29
Author(s):  
Manish Dwivedi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Targets ◽  
Cell Envelope ◽  
Intracellular Pathogen ◽  
Host Immune System ◽  
Transporter Proteins ◽  
Channel Proteins ◽  
Medical Importance ◽  
Potent Drug ◽  
Emergence Of Resistance

Scientific interest in mycobacteria has been sparked by the medical importance of Mycobacterium tuberculosis (Mtb) that is known to cause severe diseases in mammals, i.e. tuberculosis and by properties that distinguish them from other microorganisms which are notoriously difficult to treat. The treatment of their infections is difficult because mycobacteria fortify themselves with a thick impermeable cell envelope. Channel and transporter proteins are among the crucial adaptations of Mycobacterium that facilitate their strength to combat against host immune system and anti-tuberculosis drugs. In previous studies, it was investigated that some of the channel proteins contribute to the overall antibiotic resistance in Mtb. Moreover, in some of the cases, membrane proteins were found responsible for virulence of these pathogens. Given the ability of M. tuberculosis to survive as an intracellular pathogen and its inclination to develop resistance to the prevailing anti-tuberculosis drugs, its treatment requires new approaches and optimization of anti-TB drugs and investigation of new targets are needed for their potential in clinical usage. Therefore, it is imperative to investigate the survival of Mtb. in stressed conditions with different behavior of particular channel/ transporter proteins. Comprehensive understanding of channel proteins and their mechanism will provide us direction to find out preventive measures against the emergence of resistance and reduce the duration of the treatment, eventually leading to plausible eradication of tuberculosis.

scholarly journals Mechanistic insight into B(C6F5)3 catalyzed imine reduction with PhSiH3 under stoichiometric water conditions

RSC Advances ◽  
2021 ◽  
Vol 11 (34) ◽  
pp. 20961-20969
Author(s):  
Yunqing He ◽  
Wanli Nie ◽  
Ying Xue ◽  
Qishan Hu
Keyword(s):  
Mechanistic Insight ◽  
Excess Water ◽  
Water Conditions ◽  
Imine Reduction ◽  
Water Amount ◽  
Insight Into

Hydrosilylation or amination products? It depends on water amount and nucleophiles like excess water or produced/added amines.

scholarly journals Mechanistic insight into the fluorescence activity of forensic fingerprinting reagents

2021 ◽  
Vol 154 (12) ◽  
pp. 124313
Author(s):  
L. M. Hunnisett ◽  
P. F. Kelly ◽  
S. Bleay ◽  
F. Plasser ◽  
R. King ◽  
...  
Keyword(s):  
Mechanistic Insight ◽  
Insight Into
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