scholarly journals Mycobacterium tuberculosis Rv0580c Impedes the Intracellular Survival of Recombinant Mycobacteria, Manipulates the Cytokines, and Induces ER Stress and Apoptosis in Host Macrophages via NF-κB and p38/JNK Signaling

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 143
Author(s):  
Md Kaisar Ali ◽  
Lambert Nzungize ◽  
Khushnood Abbas ◽  
Nzaou Stech Anomene Eckzechel ◽  
M. A. Abo-kadoum ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Er Stress ◽  
Hypothetical Protein ◽  
Intracellular Survival ◽  
Marker Genes ◽  
Jnk Signaling ◽  
Host Interaction ◽  
Recombinant Mycobacterium Smegmatis

The Mycobacterium tuberculosis (M. tb) genome encodes a large number of hypothetical proteins, which need to investigate their role in physiology, virulence, pathogenesis, and host interaction. To explore the role of hypothetical protein Rv0580c, we constructed the recombinant Mycobacterium smegmatis (M. smegmatis) strain, which expressed the Rv0580c protein heterologously. We observed that Rv0580c expressing M. smegmatis strain (Ms_Rv0580c) altered the colony morphology and increased the cell wall permeability, leading to this recombinant strain becoming susceptible to acidic stress, oxidative stress, cell wall-perturbing stress, and multiple antibiotics. The intracellular survival of Ms_Rv0580c was reduced in THP-1 macrophages. Ms_Rv0580c up-regulated the IFN-γ expression via NF-κB and JNK signaling, and down-regulated IL-10 expression via NF-κB signaling in THP-1 macrophages as compared to control. Moreover, Ms_Rv0580c up-regulated the expression of HIF-1α and ER stress marker genes via the NF-κB/JNK axis and JNK/p38 axis, respectively, and boosted the mitochondria-independent apoptosis in macrophages, which might be lead to eliminate the intracellular bacilli. This study explores the crucial role of Rv0580c protein in the physiology and novel host-pathogen interactions of mycobacteria.

Rv2223c, an acid inducible carboxyl-esterase of Mycobacterium tuberculosis enhanced the growth and survival of Mycobacterium smegmatis

2019 ◽  
Vol 14 (16) ◽  
pp. 1397-1415
Author(s):  
Pratibha Maan ◽  
Jagdeep Kaur
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Intracellular Survival ◽  
Growth And Survival ◽  
Enhanced Expression ◽  
Stress Environment ◽  
In Vitro Stress ◽  
Carboxyl Esterase

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis ( MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.

scholarly journals c-Jun-N-Terminal Kinase Signaling Is Involved in Cyclosporine-Induced Epithelial Phenotypic Changes

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Nicolas Pallet ◽  
Eric Thervet ◽  
Dany Anglicheau
Keyword(s):  
Epithelial Cells ◽  
Er Stress ◽  
Epithelial To Mesenchymal Transition ◽  
Primary Cultures ◽  
Independent Manner ◽  
Jnk Signaling ◽  
Mesenchymal Transition ◽  
Morphological Alterations ◽  
Phenotypic Changes

Tubular epithelial cells play a central role in the pathogenesis of chronic nephropathies. Previous toxicogenomic studies have demonstrated that cyclosporine- (CsA-) induced epithelial phenotypic changes (EPCs) are reminiscent of an incomplete epithelial to mesenchymal transition (EMT) in a TGF-β-independent manner. Furthermore, we identified endoplasmic reticulum (ER) stress as a potential mechanism that may participate in the modulation of tubular cell plasticity during CsA exposure. Because c-jun-N-terminal kinase (JNK), which is activated during ER stress, is implicated in kidney fibrogenesis, we undertook the current study to identify the role of JNK signaling in EPCs induced by CsA. In primary cultures of human renal epithelial cells, CsA activates JNK signaling, and the treatment with a JNK inhibitor reduces the occurrence of cell shape changes, E-cadherin downregulation, cell migration, and Snail-1 expression. Our results suggest that CsA activates JNK signaling, which, in turn, may participate in the morphological alterations through the regulation of Snail-1 expression.

scholarly journals Mycobacterium tuberculosis Thymidylyltransferase RmlA Is Negatively Regulated by Ser/Thr Protein Kinase PknB

2021 ◽  
Vol 12 ◽  
Author(s):  
Dehui Qu ◽  
Xiaohui Zhao ◽  
Yao Sun ◽  
Fan-Lin Wu ◽  
Sheng-Ce Tao
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Catalytic Triad ◽  
Mass Spectrometry Analysis ◽  
Wall Structure ◽  
Cell Wall Formation ◽  
Phenotypic Analysis ◽  
Spectrometry Analysis ◽  
Wall Formation

Ser/Thr phosphorylation by serine/threonine protein kinases (STPKs) plays significant roles in molecular regulation, which allows Mycobacteria to adapt their cell wall structure in response to the environment changes. Identifying direct targets of STPKs and determining their activities are therefore critical to revealing their function in Mycobacteria, for example, in cell wall formation and virulence. Herein, we reported that RmlA, a crucial L-rhamnose biosynthesis enzyme, is a substrate of STPK PknB in Mycobacterium tuberculosis (M. tuberculosis). Mass spectrometry analysis revealed that RmlA is phosphorylated at Thr-12, Thr-54, Thr-197, and Thr-12 is located close to the catalytic triad of RmlA. Biochemical and phenotypic analysis of two RmlA mutants, T12A/T12D, showed that their activities were reduced, and cell wall formation was negatively affected. Moreover, virulence of RmlA T12D mutant was attenuated in a macrophage model. Overall, these results provide the first evidence for the role of PknB-dependent RmlA phosphorylation in regulating cell wall formation in Mycobacteria, with significant implications for pathogenicity.

scholarly journals Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Catherine Baranowski ◽  
Michael A Welsh ◽  
Lok-To Sham ◽  
Haig A Eskandarian ◽  
Hoong Chuin Lim ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Uniform Distribution ◽  
Genetic Relationship ◽  
Mycobacterium Smegmatis ◽  
Drug Targets ◽  
Polar Growth ◽  
Penicillin Binding Proteins ◽  
Aging Cell

In most well-studied rod-shaped bacteria, peptidoglycan is primarily crosslinked by penicillin-binding proteins (PBPs). However, in mycobacteria, crosslinks formed by L,D-transpeptidases (LDTs) are highly abundant. To elucidate the role of these unusual crosslinks, we characterized Mycobacterium smegmatis cells lacking all LDTs. We find that crosslinks generate by LDTs are required for rod shape maintenance specifically at sites of aging cell wall, a byproduct of polar elongation. Asymmetric polar growth leads to a non-uniform distribution of these two types of crosslinks in a single cell. Consequently, in the absence of LDT-mediated crosslinks, PBP-catalyzed crosslinks become more important. Because of this, Mycobacterium tuberculosis (Mtb) is more rapidly killed using a combination of drugs capable of PBP- and LDT- inhibition. Thus, knowledge about the spatial and genetic relationship between drug targets can be exploited to more effectively treat this pathogen.

Role of the Major Antigen of Mycobacterium tuberculosis in Cell Wall Biogenesis

Science ◽  
1997 ◽  
Vol 276 (5317) ◽  
pp. 1420-1422 ◽  
Author(s):  
J. T. Belisle
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Cell Wall Biogenesis ◽  
Major Antigen

Role of two‐component regulatory systems in intracellular survival of Mycobacterium tuberculosis

2019 ◽  
Vol 120 (8) ◽  
pp. 12197-12207
Author(s):  
Xue Li ◽  
Xi Lv ◽  
Yanping Lin ◽  
Junfeng Zhen ◽  
Cao Ruan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Intracellular Survival ◽  
Regulatory Systems ◽  
Two Component

scholarly journals Maturing Mycobacterial Peptidoglycan Requires Non-canonical Crosslinks to Maintain Shape

2018 ◽  
Author(s):  
Catherine Baranowski ◽  
Michael A. Welsh ◽  
Lok-To Sham ◽  
Haig A. Eskandarian ◽  
Hoong C. Lim ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Single Cell ◽  
Uniform Distribution ◽  
Drug Targets ◽  
Polar Growth ◽  
Cell Distribution ◽  
Penicillin Binding Proteins ◽  
Aging Cell

AbstractIn most well studied rod-shaped bacteria, peptidoglycan is primarily crosslinked by penicillin binding proteins (PBPs). However, in mycobacteria, L,D-transpeptidase (LDT)-mediated crosslinks are highly abundant. To elucidate the role of these unusual crosslinks, we characterized mycobacterial cells lacking all LDTs. We find that LDT-mediated crosslinks are required for rod shape maintenance specifically at sites of aging cell wall, a byproduct of polar elongation. Asymmetric polar growth leads to a non-uniform distribution of these two types of crosslinks in a single cell. Consequently, in the absence of LDT-mediated crosslinks, PBP-catalyzed crosslinks become more important. Because of this,Mycobacterium tuberculosis(Mtb) is more rapidly killed using a combination of drugs capable of PBP- and LDT-inhibition. Thus, knowledge about the single-cell distribution of drug targets can be exploited to more effectively treat this pathogen.

scholarly journals Role of Protein Glycosylation in Candida parapsilosis Cell Wall Integrity and Host Interaction

2016 ◽  
Vol 7 ◽  
Author(s):  
Luis A. Pérez-García ◽  
Katalin Csonka ◽  
Arturo Flores-Carreón ◽  
Eine Estrada-Mata ◽  
Erika Mellado-Mojica ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Parapsilosis ◽  
Protein Glycosylation ◽  
Cell Wall Integrity ◽  
Host Interaction
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