From Genome to Proteome to Elucidation of Reactions for All Eleven Known Lytic Transglycosylases from <i>Pseudomonas aeruginosa</i>

Lee, Mijoon; Hesek, Dušan; Dik, David A.; Fishovitz, Jennifer; Lastochkin, Elena; Boggess, Bill; Fisher, Jed F.; Mobashery, Shahriar

doi:10.1002/ange.201611279

Cited by 9 publications

(14 citation statements)

References 26 publications

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“…Indeed, in vitro studies show that with few exception, the catalytic reactions of LTs overlap. 257,258 Most LTs are membrane-bound (designated as "Mlt" LTs) lipoproteins anchored to the inner leaflet of the outer membrane. At least one LT is anchored to the outer leaflet of the inner membrane (the MltG, which the reader recalls, regulates the nascent-glycan strand sizing).…”

Section: Lytic Transglycosylases: Liberation Of Cell-wall Fragmentsmentioning

confidence: 99%

Cell-Wall Recycling of the Gram-Negative Bacteria and the Nexus to Antibiotic Resistance

2018

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The importance of the cell wall to the viability of the bacterium is underscored by the breadth of antibiotic structures that act by blocking key enzymes that are tasked with cell-wall creation, preservation, and regulation. The interplay between cell-wall integrity, and the summoning forth of resistance mechanisms to deactivate cell-wall-targeting antibiotics, involves exquisite orchestration among cell-wall synthesis and remodeling and the detection of and response to the antibiotics through modulation of gene regulation by specific effectors. Given the profound importance of antibiotics to the practice of medicine, the assertion that understanding this interplay is among the most fundamentally important questions in bacterial physiology is credible. The enigmatic regulation of the expression of the AmpC β-lactamase, a clinically significant and highly regulated resistance response of certain Gram-negative bacteria to the β-lactam antibiotics, is the exemplar of this challenge. This review gives a current perspective to this compelling, and still not fully solved, 35-year enigma.

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Section: Lytic Transglycosylases: Liberation Of Cell-wall Fragmentsmentioning

confidence: 99%

Cell-Wall Recycling of the Gram-Negative Bacteria and the Nexus to Antibiotic Resistance

2018

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“…This observation is likely due to the multiplicity of LTs, 11 are known in P. aeruginosa, with overlapping redundant activities. 27 Not all of the 11 LTs are expected to be inhibited by bulgecin A. 50 Bulgecin A potentiation of a clinical β-lactam antibiotic was visualized by microscopy.…”

Section: Acs Infectious Diseasesmentioning

confidence: 99%

Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics

et al. 2018

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The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mechanism of a cobiosynthesized β-lactam antibiotic. β-Lactams inhibit the penicillin-binding proteins, enzymes also critical to cell-wall biosynthesis. The simultaneous loss of the lytic transglycosylase (by bulgecin) and penicillin-binding protein (by β-lactams) activities results in deformation of the septal cell wall, observed microscopically as a bulge preceding bacterial cell lysis. We describe a practical synthesis of the three naturally occurring bulgecin iminosaccharides and their mechanistic evaluation in a series of microbiological studies. These studies identify potentiation by the bulgecin at subminimum inhibitory concentrations of the β-lactam against three pathogenic Gram-negative bacteria and establish for the first time that this potentiation results in a significant increase in the bactericidal efficacy of a clinical β-lactam.

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“…Synthetic peptidoglycans 1 – 3 were prepared for this study by multi-step syntheses reported previously [44] , [45] , [46] .…”

Section: Methodsmentioning

confidence: 99%

Integrative structural biology of the penicillin-binding protein-1 from Staphylococcus aureus, an essential component of the divisome machinery

Martínez-Caballero

Mahasenan

Kim

et al. 2021

Computational and Structural Biotechnology Journal

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From Genome to Proteome to Elucidation of Reactions for All Eleven Known Lytic Transglycosylases from Pseudomonas aeruginosa

Cited by 9 publications

References 26 publications

Cell-Wall Recycling of the Gram-Negative Bacteria and the Nexus to Antibiotic Resistance

Cell-Wall Recycling of the Gram-Negative Bacteria and the Nexus to Antibiotic Resistance

Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics

Integrative structural biology of the penicillin-binding protein-1 from Staphylococcus aureus, an essential component of the divisome machinery

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