scholarly journals Newly Discovered Cell Shape Promoting Protein Complex Involved in the Maintenance of Distinct Helical Shape of Helicobacter Pylori

2019 ◽  
pp. 28-30
Author(s):  
Freeman Paczkowski
Keyword(s):  
Cell Wall ◽  
Helicobacter Pylori ◽  
Cell Shape ◽  
Drug Target ◽  
Clinical Implications ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Multiple Cell ◽  
H Pylori ◽  
Cell Shape Formation

The distinct helical shape of the bacterium Helicobacter Pylori (H. pylori) assists this organism in colonizing the digestive organs of its target host. It has been discovered that a key determinant of helical cell shape formation in H. pylori is the Csd5 protein, which engages in multiple cell shape promoting interactions with the cell wall and other various proteins. This finding has significant clinical implications, as it outlines Csd5 as a potential drug target for treating H. pylori infection in the future.

scholarly journals A Genome-WideHelicobacter pyloriMorphology Screen Uncovers a Membrane-Spanning Helical Cell Shape Complex

2019 ◽  
Vol 201 (14) ◽  
Author(s):  
Desirée C. Yang ◽  
Kris M. Blair ◽  
Jennifer A. Taylor ◽  
Timothy W. Petersen ◽  
Tate Sessler ◽  
...  
Keyword(s):  
Cell Wall ◽  
Helicobacter Pylori ◽  
Light Scattering ◽  
Protein Interactions ◽  
Cell Morphology ◽  
Cell Shape ◽  
Cross Linking ◽  
Protein Protein Interactions ◽  
Content Type ◽  
H Pylori

ABSTRACTEvident in its name, the gastric pathogenHelicobacter pylorihas a helical cell morphology which facilitates efficient colonization of the human stomach. An improved light-focusing strategy allowed us to robustly distinguish even subtle perturbations ofH. pyloricell morphology by deviations in light-scattering properties measured by flow cytometry. Profiling of an arrayed genome-wide deletion library identified 28 genes that influence different aspects of cell shape, including properties of the helix, cell length or width, cell filament formation, cell shape heterogeneity, and cell branching. Included in this mutant collection were two that failed to form any helical cells, a soluble lytic transglycosylase and a previously uncharacterized putative multipass inner membrane protein HPG27_0728, renamed Csd7. A combination of cell fractionation, mutational, and immunoprecipitation experiments show that Csd7 and Csd2 collaborate to stabilize the Csd1 peptidoglycan (PG) endopeptidase. Thus, bothcsd2andcsd7mutants show the same enhancement of PG tetra-pentapeptide cross-linking ascsd1mutants. Csd7 also links Csd1 with the bactofilin CcmA via protein-protein interactions. Although Csd1 is stable inccmAmutants, these mutants show altered PG tetra-pentapeptide cross-linking, suggesting that Csd7 may directly or indirectly activate as well as stabilize Csd1. These data begin to illuminate a highly orchestrated program to regulate PG modifications that promote helical shape, which includes nine nonessential nonredundant genes required for helical shape and 26 additional genes that further modifyH. pylori’s cell morphology.IMPORTANCEThe stomach ulcer and cancer-causing pathogenHelicobacter pylorihas a helical cell shape which facilitates stomach infection. Using light scattering to measure perturbations of cell morphology, we identified 28 genes that influence different aspects of cell shape. A mutant in a previously uncharacterized protein renamed Csd7 failed to form any helical cells. Biochemical analyses showed that Csd7 collaborates with other proteins to stabilize the cell wall-degrading enzyme Csd1. Csd7 also links Csd1 with a putative filament-forming protein via protein-protein interactions. These data suggest that helical cell shape arises from a highly orchestrated program to regulate cell wall modifications. Targeting of this helical cell shape-promoting program could offer new ways to block infectivity of this important human pathogen.

scholarly journals Identification and Characterization of a Major Cell Wall-Associated Iron-Regulated Envelope Protein (Irep-28) in Mycobacterium tuberculosis

2006 ◽  
Vol 13 (10) ◽  
pp. 1137-1142 ◽  
Author(s):  
Veena C. Yeruva ◽  
Sridevi Duggirala ◽  
V. Lakshmi ◽  
Daniel Kolarich ◽  
Friedrich Altmann ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Envelope Protein ◽  
Drug Target ◽  
Iron Limitation ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Tuberculosis Patients ◽  
Identification And Characterization

ABSTRACTIron limitation and the expression of mycobactin and carboxymycobactin byMycobacterium tuberculosisare known. Here, we report how iron regulated the coordinate expression of these two siderophores and a 28-kDa cell wall-associated iron-regulated protein (Irep-28). Irep-28 is identified as the DNA-binding HU homologue HupB protein (hupB[Rv2986c]). Antibodies to this protein were detected in sera from tuberculosis patients. The location of the protein in the cell wall makes it a potential drug target.

The Prokaryotic FAD Synthetase Family: A Potential Drug Target

2013 ◽  
Vol 19 (14) ◽  
pp. 2637-2648 ◽  
Author(s):  
Ana Serrano ◽  
Patricia Ferreira ◽  
Marta Martinez-Julvez ◽  
Milagros Medina
Keyword(s):  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug

Bacterial Polyphosphate Kinases Revisited: Role in Pathogenesis and Therapeutic Potential

2019 ◽  
Vol 20 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Lalit Kumar Gautam ◽  
Prince Sharma ◽  
Neena Capalash
Keyword(s):  
Drug Target ◽  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Wide Distribution ◽  
Medical Community ◽  
Polyphosphate Kinase ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Resistant Strains ◽  
Structural Aspects

Bacterial infections have always been an unrestrained challenge to the medical community due to the rise of multi-drug tolerant and resistant strains. Pioneering work on Escherichia coli polyphosphate kinase (PPK) by Arthur Kornberg has generated great interest in this polyphosphate (PolyP) synthesizing enzyme. PPK has wide distribution among pathogens and is involved in promoting pathogenesis, stress management and susceptibility to antibiotics. Further, the absence of a PPK orthologue in humans makes it a potential drug target. This review covers the functional and structural aspects of polyphosphate kinases in bacterial pathogens. A description of molecules being designed against PPKs has been provided, challenges associated with PPK inhibitor design are highlighted and the strategies to enable development of efficient drug against this enzyme have also been discussed.

Molecular Docking with Trehalose-6 Phosphate Phosphatase: A Potential Drug Target of Filaral Parasite ‘Brugia malayi’

2011 ◽  
Vol 8 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Lakshminarayanan Karthik ◽  
Palayam Malathy ◽  
Annie Trinitta ◽  
Krishnasamy Gunasekaran
Keyword(s):  
Molecular Docking ◽  
Drug Target ◽  
Brugia Malayi ◽  
Potential Drug Target ◽  
Potential Drug

scholarly journals Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe

2021 ◽  
Author(s):  
Nattawadee Panyain ◽  
Aurélien Godinat ◽  
Aditya Raymond Thawani ◽  
Sofía Lachiondo-Ortega ◽  
Katie Mason ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Lung Fibrosis ◽  
Drug Target ◽  
Protein Profiling ◽  
Deubiquitinating Enzyme ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Bona Fide ◽  
Carboxy Terminal

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme (DUB), is a potential drug target in various cancers, and liver and lung fibrosis. However, bona fide functions and substrates of UCHL1...

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