Use of Bacterial Cell Wall Recycle Inhibitors to Combat Antimicrobial Resistance

Raghavan, Ramya; Mandal, Jharna

doi:10.1007/978-981-15-3658-8_9

Cited by 2 publications

(2 citation statements)

References 69 publications

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“…The close relationship between GHs and GPs is particularly striking in the retaining family GH3. This family contains β- N -acetylglucosaminidases, often referred to as NagZs, which have been studied quite extensively as their reaction also regulates gene expression for β-lactamase, making them attractive targets for drug design to combat antibiotic resistance. − In 2015, the Withers group discovered that the N -acetylglucosaminidase from Cellulomonas fimi, which had already been characterized a decade earlier, actually is a phosphorylase rather than a hydrolase . They hypothesized that the need of this enzyme to accommodate phosphate explains why it uses a histidine as the catalytic acid/base residue, while this role is fulfilled by an anionic glutamate residue in the hydrolases within this family (also comprising β- d -xylopyranosidases, β- d -glucosidases, and α- l -arabinofuranosidases) .…”

Section: Introductionmentioning

confidence: 99%

Evolution of Phosphorylases from N-Acetylglucosaminide Hydrolases in Family GH3

et al. 2021

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Glycoside phosphorylases hold great potential as catalysts for the synthesis of valuable sugars, glycosides, and glycans or for the development of energy-efficient microbial cell factories. However, the number of available phosphorylase specificities is rather limited. Here, we show that it is possible to establish significant phosphorylase activity in GH3 glycoside hydrolases from Pseudomonas aeruginosa and Bacillus subtilis. Single-site substitutions could introduce the ability to produce glycosyl phosphates, and a combinatorial saturation study demonstrated that this promiscuous side activity can be further optimized through various mutational paths. These findings suggest that future endeavors for the development of phosphorylases could start from hydrolases as engineering templates. In addition, we provide further insights into the elusive determinants of phosphorylase activity in natural GH3 phosphorylases.

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Section: Introductionmentioning

confidence: 99%

Evolution of Phosphorylases from N-Acetylglucosaminide Hydrolases in Family GH3

et al. 2021

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“…The rapid development of multidrug resistance in most microbial pathogens is the main motivation for the rapid development and creation of drugs with new alternative molecular mechanisms of action [2]. It is known that bacterial TG are used as a promising target for the development of new antimicrobial drugs [3][4]. On the other hand, such antifungal agents as caspofungin, anidulafungin and micafungin are inhibitors of 1,3-beta-glucan synthase (EC 2.4.1.34) from the transglycosylase family and participate in the formation of the main component of the fungal cell wall -beta-1,3-glucan polymer [5][6].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in silico study of 1,3-oxazol-4-yltriphenylphosphonium salts as potential inhibitors of Candida albicans transglycosylase

et al. 2021

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The previously established in vitro high antimicrobial potential of triphenylphosphonium salts (TPPs) against bacterial (Staphylococcus aureus ATCC 25923 and multi-drug resistant (MDR)) and fungal (Candida albicans ATCC 10231 and MDR) strains made it possible to propose a molecular mechanism of action of these compounds associated with transglycosylase (TG) activity. The hypothesis was based on the well-known literature data on TPPs as inhibitors of S. aureus TG. The created homology model of TG C. albicans is optimal in terms of such quality indicators as GMQE (0.61), ERRAT (overall quality factor 95.904) and Ramachandran plot analysis (90% amino acid residues in the favored regions). Molecular docking of the most active ligands 1a-d, 3c into the active center of the created homology C. albicans TG model demonstrated the formation of stable ligand-protein complexes with binding energies in the range from -8.9 to -9.7 kcal/mol due to the various types of interactions. An important role in complex formation belongs to amino acid residues TYR307, TYR107, GLU275, ALA108 and PRO136. The presented qualitative homologous model of C. albicans TG can be used to search and create new agents with a dual mechanism of antimicrobial action. 1,3-oxazol-4-yltriphenylphosphonium salts 1a-d, 3c perform the perspective objects for further study as antimicrobials against infectious MDR pathogens.

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Use of Bacterial Cell Wall Recycle Inhibitors to Combat Antimicrobial Resistance

Cited by 2 publications

References 69 publications

Evolution of Phosphorylases from N-Acetylglucosaminide Hydrolases in Family GH3

Evolution of Phosphorylases from N-Acetylglucosaminide Hydrolases in Family GH3

In vitro and in silico study of 1,3-oxazol-4-yltriphenylphosphonium salts as potential inhibitors of Candida albicans transglycosylase

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