Synthetic Glycolipids As A New Class Of Antimicrobials To Down-regulate Cell Wall Functions

2017 ◽  
Author(s):  
Narayanaswamy Jayaraman
Keyword(s):  
Cell Wall ◽  
Wall Functions ◽  
New Class

scholarly journals Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1141
Author(s):  
Richard M. Beteck ◽  
Audrey Jordaan ◽  
Ronnett Seldon ◽  
Dustin Laming ◽  
Heinrich C. Hoppe ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protozoan Parasites ◽  
Trypanosoma Brucei Brucei ◽  
New Class ◽  
High Lipid ◽  
Host Infection ◽  
Eskape Pathogens ◽  
Quinolone Derivatives ◽  
Lipophilic Character

The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites (Plasmodium falciparum and Trypanosoma brucei brucei) and against ESKAPE pathogens. The resultant compounds exhibited varied anti-Mtb activity with MIC90 values in the range of 0.24–31 µM. Cross-screening against P. falciparum and T.b. brucei, identified several compounds with antiprotozoal activities in the range of 0.4–20 µM. Compounds were generally inactive against ESKAPE pathogens, with only compounds 8c, 8g and 13 exhibiting moderate to poor activity against S. aureus and A. baumannii.

Transcriptome profiling of aSaccharomyces cerevisiaemutant with a constitutively activated Ras/cAMP pathway

2003 ◽  
Vol 16 (1) ◽  
pp. 107-118 ◽  
Author(s):  
D. L. Jones ◽  
J. Petty ◽  
D. C. Hoyle ◽  
A. Hayes ◽  
E. Ragni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Wall ◽  
Microarray Analysis ◽  
Cellular Response ◽  
Ribosome Biogenesis ◽  
Biological Significance ◽  
Altered Expression ◽  
Wall Functions ◽  
Constitutive Activation ◽  
Camp Pathway

Often changes in gene expression levels have been considered significant only when above/below some arbitrarily chosen threshold. We investigated the effect of applying a purely statistical approach to microarray analysis and demonstrated that small changes in gene expression have biological significance. Whole genome microarray analysis of a pde2Δ mutant, constructed in the Saccharomyces cerevisiae reference strain FY23, revealed altered expression of ∼11% of protein encoding genes. The mutant, characterized by constitutive activation of the Ras/cAMP pathway, has increased sensitivity to stress, reduced ability to assimilate nonfermentable carbon sources, and some cell wall integrity defects. Applying the Munich Information Centre for Protein Sequences (MIPS) functional categories revealed increased expression of genes related to ribosome biogenesis and downregulation of genes in the cell rescue, defense, cell death and aging category, suggesting a decreased response to stress conditions. A reduced level of gene expression in the unfolded protein response pathway (UPR) was observed. Cell wall genes whose expression was affected by this mutation were also identified. Several of the cAMP-responsive orphan genes, upon further investigation, revealed cell wall functions; others had previously unidentified phenotypes assigned to them. This investigation provides a statistical global transcriptome analysis of the cellular response to constitutive activation of the Ras/cAMP pathway.

scholarly journals Yeast actin cytoskeleton mutants accumulate a new class of Golgi-derived secretary vesicle.

1997 ◽  
Vol 8 (8) ◽  
pp. 1481-1499 ◽  
Author(s):  
J Mulholland ◽  
A Wesp ◽  
H Riezman ◽  
D Botstein
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Actin Cytoskeleton ◽  
Biochemical Analysis ◽  
Small Gtpase ◽  
Secretory Vesicles ◽  
Cytoskeleton Organization ◽  
New Class ◽  
Actin Cytoskeleton Organization ◽  
Vectorial Transport

Many yeast actin cytoskeleton mutants accumulate large secretory vesicles and exhibit phenotypes consistent with defects in polarized growth. This, together with actin's polarized organization, has suggested a role for the actin cytoskeleton in the vectorial transport of late secretory vesicles to the plasma membrane. By using ultrastructural and biochemical analysis, we have characterized defects manifested by mutations in the SLA2 gene (also known as the END4 gene), previously found to affect both the organization of the actin cytoskeleton and endocytosis in yeast. Defects in cell wall morphology, accumulated vesicles, and protein secretion kinetics were found in sla2 mutants similar to defects found in act1 mutants. Vesicles that accumulate in the sla2 and act1 mutants are immunoreactive with antibodies directed against the small GTPase Ypt1p but not with antibodies directed against the homologous Sec4p found on classical "late" secretory vesicles. In contrast, the late-acting secretory mutants sec1-1 and sec6-4 are shown to accumulate anti-Sec4p-positive secretory vesicles as well as vesicles that are immunoreactive with antibodies directed against Ypt1p. The late sec mutant sec4-8 is also shown to accumulate Ypt1p-containing vesicles and to exhibit defects in actin cytoskeleton organization. These results indicate the existence of at least two classes of morphologically similar, late secretory vesicles (associated with Ypt1p+ and Sec4p+, respectively), one of which appears to accumulate when the actin cytoskeleton is disorganized.

Roles of VPH2 and VMA6 in localization of V-ATPase subunits, cell wall functions and filamentous development in Candida albicans

2018 ◽  
Vol 114 ◽  
pp. 1-11 ◽  
Author(s):  
Chang Jia ◽  
Kai Zhang ◽  
Dan Zhang ◽  
Qilin Yu ◽  
Qiang Zhao ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Wall Functions ◽  
Atpase Subunits

The ‘yeast cell wall chip’ – a tool to analyse the regulation of cell wall biogenesis in Saccharomyces cerevisiae

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2241-2249 ◽  
Author(s):  
Jose M. Rodríguez-Peña ◽  
Rosa M. Pérez-Díaz ◽  
Sara Alvarez ◽  
Clara Bermejo ◽  
Raúl García ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Yeast Cell ◽  
Transcriptional Activation ◽  
Ease Of Use ◽  
Yeast Cell Wall ◽  
Gene Microarray ◽  
Experimental Conditions ◽  
Wall Functions ◽  
Cell Wall Damage

Within the field of Saccharomyces cerevisiae functional genomics, DNA microarrays have become a very useful tool to study genome-wide gene-expression changes under diverse experimental conditions. Here, the design and production of a gene microarray, called the ‘yeast cell wall chip’, specifically tailored to investigate cell wall functions, is described. This array has been validated and shown to be useful to address gene involvement in the regulation of the response to cell wall damage in yeast. The advantages of this tailored gene microarray, which contains 390 genes, in terms of reproducibility, accuracy, versatility and ease of use are reported. Importantly, the microarray design permits the performance of a double hybridization process (two experiments) on the same slide. Cell wall stress leads to the transcriptional activation of a set of genes involved in cell wall remodelling. This response has been shown to be strongly controlled by the MAP kinase (MAPK) Slt2p, but other signalling pathways have also been suggested to be involved in this process. Here, using the tailored microarray, the role of the HOG1 pathway in the regulation of the transcriptional compensatory response to cell wall damage was evaluated by comparing the transcriptional profiles of a hog1 mutant and a wild-type strain in the presence of Congo red. Two genes, YFL014W (HSP12) and YLR414C, were found to be dependent on the Hog1p MAPK for their induction, indicating that an additional level of regulation of cell wall functions is mediated by this MAPK.

Combinatorial enzymatic assay for the screening of a new class of bacterial cell wall inhibitors

2003 ◽  
Vol 11 (7) ◽  
pp. 1583-1592 ◽  
Author(s):  
Ahmed El Zoeiby ◽  
Mélanie Beaumont ◽  
Eric Dubuc ◽  
François Sanschagrin ◽  
Normand Voyer ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Bacterial Cell Wall ◽  
Enzymatic Assay ◽  
New Class

scholarly journals A New Class of Cell Wall-Recycling l , d -Carboxypeptidase Determines β-Lactam Susceptibility and Morphogenesis in Acinetobacter baumannii

mBio ◽  
2021 ◽  
Author(s):  
Yunfei Dai ◽  
Victor Pinedo ◽  
Amy Y. Tang ◽  
Felipe Cava ◽  
Edward Geisinger
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Enzymatic Activity ◽  
Acinetobacter Baumannii ◽  
Drug Resistant ◽  
Content Type ◽  
New Class ◽  
Recycling Pathway ◽  
And Control ◽  
Cell Wall Recycling

To grow efficiently, resist antibiotics, and control the immune response, bacteria recycle parts of their cell wall. A key step in the typical recycling pathway is the reuse of cell wall peptides by an enzyme known as an l , d -carboxypeptidase (LDC). Acinetobacter baumannii , an “urgent-threat” pathogen causing drug-resistant sepsis in hospitals, was previously thought to lack this enzymatic activity due to absence of a known LDC homolog.

scholarly journals Sortase B, a New Class of Sortase in Listeria monocytogenes

2004 ◽  
Vol 186 (7) ◽  
pp. 1972-1982 ◽  
Author(s):  
Hélène Bierne ◽  
Caroline Garandeau ◽  
M. Graciela Pucciarelli ◽  
Christophe Sabet ◽  
Salete Newton ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Listeria Monocytogenes ◽  
Virulence Factor ◽  
Cultured Cells ◽  
Surface Proteins ◽  
Gram Positive Bacteria ◽  
New Class ◽  
Sorting Motif

ABSTRACT Sortases are transamidases that covalently link proteins to the peptidoglycan of gram-positive bacteria. The genome of the pathogenic bacterium Listeria monocytogenes encodes two sortases genes, srtA and srtB. The srtA gene product anchors internalin and some other LPXTG-containing proteins to the listerial surface. Here, we focus on the role of the second sortase, SrtB. Whereas SrtA acts on most of the proteins in the peptidoglycan fraction, SrtB appears to target minor amounts of surface polypeptides. We identified one of the SrtB-anchored proteins as the virulence factor SvpA, a surface-exposed protein which does not contain the LPXTG motif. Therefore, as in Staphylococcus aureus, the listerial SrtB represents a second class of sortase in L. monocytogenes, involved in the attachment of a subset of proteins to the cell wall, most likely by recognizing an NXZTN sorting motif. The ΔsrtB mutant strain does not have defects in bacterial entry, growth, or motility in tissue-cultured cells and does not show attenuated virulence in mice. SrtB-mediated anchoring could therefore be required to anchor surface proteins involved in the adaptation of this microorganism to different environmental conditions.

scholarly journals An Ultraefficient Affinity-Based High-Throughout Screening Process: Application to Bacterial Cell Wall Biosynthesis Enzyme MurF

2006 ◽  
Vol 11 (7) ◽  
pp. 743-754 ◽  
Author(s):  
Kenneth M. Comess ◽  
Mark E. Schurdak ◽  
Martin J. Voorbach ◽  
Michael Coen ◽  
Jonathan D. Trumbull ◽  
...  
Keyword(s):  
Cell Wall ◽  
Organic Molecules ◽  
Screening Method ◽  
Screening Process ◽  
Protein Targets ◽  
Small Organic Molecules ◽  
Protein Target ◽  
New Class ◽  
Equilibrium Binding ◽  
Ligand Identification

The authors describe the discovery of a new class of inhibitors to an essential Streptococcus pneumoniae cell wall biosyn-thesis enzyme, MurF, by a novel affinity screening method. The strategy involved screening very large mixtures of diverse small organic molecules against the protein target on the basis of equilibrium binding, followed by iterative ultrafiltration steps and ligand identification by mass spectrometry. Hits from any affinity-based screening method often can be relatively nonselective ligands, sometimes referred to as “nuisance” or “promiscuous” compounds. Ligands selective in their binding affinity for the MurF target were readily identified through electronic subtraction of an empirically determined subset of promiscuous compounds in the library without subsequent selectivity panels. The complete strategy for discovery and identification of novel specific ligands can be applied to all soluble protein targets and a wide variety of ligand libraries.

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