Discovery and Development of the Monobactams

Sykes, R. B.; Bonner, Daniel P.

doi:10.1093/clinids/7.supplement_4.s579

Cited by 74 publications

(52 citation statements)

References 25 publications

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“…The ␤-lactam antibiotic aztreonam binds PBP 3 and causes E. coli to filament due to the inactivation of this essential PBP, which is intimately involved in the formation of septal peptidoglycan (2, 9). For some time, aztreonam has been used as a PBP 3-specific antibiotic in studies of septation, because in competitive binding assays aztreonam binds most strongly to PBP 3 (42). We reconfirmed previous observations (13) that AmpC binds aztreonam just as strongly as does PBP 3.…”

Section: Identification and Subcloning Of Newsupporting

confidence: 85%

AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli

et al. 1997

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Two proteins that bind penicillin were observed in Escherichia coli infected with phages 141, 142, 650, and 651 from the Kohara genomic library. These phages carry chromosomal DNA fragments that do not contain any known penicillin binding protein (PBP) genes, indicating that unrecognized gene products were exhibiting penicillin binding activity. The genes encoding these proteins were subcloned, sequenced, and identified. One gene was ampC, which encodes a chromosomal class C ␤-lactamase. The second gene was located at about 8.5 min on the E. coli genomic map and is a previously uncharacterized open reading frame, here named ampH, that encodes a protein closely related to the class C ␤-lactamases. The predicted AmpH protein is similar in length to AmpC, but there are extensive alterations in the amino acid sequence between the SXXK and YXN motifs of the two proteins. AmpH bound strongly to penicillin G, cefoxitin, and cephalosporin C; was temperature sensitive; and disappeared from cells after overnight incubation in stationary phase. Although closely related to AmpC and other class C ␤-lactamases, AmpH showed no ␤-lactamase activity toward the substrate nitrocefin. Mutation of the ampC and/or ampH genes in E. coli lacking PBPs 1a and 5 produced morphologically aberrant cells, particularly in cell filaments induced by aztreonam. Thus, these two members of the ␤-lactamase family exhibit characteristics similar to those of the classical PBPs, and their absence affects cell morphology. These traits suggest that AmpC and AmpH may play roles in the normal course of peptidoglycan synthesis, remodeling, or recycling.

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Section: Identification and Subcloning Of Newsupporting

confidence: 85%

AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli

et al. 1997

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“…The biotinylated sacculi were visualized by treating with rabbit antibiotin antiserum followed by Cy3-labelled goat anti-rabbit antibody. The chasing was done in the presence of aztreonam; this monolactam antibiotic blocks the action of PBP 3 (Sykes et al, 1986), which is involved in the constriction and cell division process and thus leads to filamentous growth. Portions of a single picture of many cells obtained with the fluorescence microscope after either a oneor two-doubling-time chase, published as Fig.…”

Section: Methodsmentioning

confidence: 99%

“…The chases were carried out under conditions that blocked cell division and led to filament formation. The action of aztreonam leading to filament formation is the inhibition of PBP 3 (Sykes et al, 1986). If some divisions had completed during the chase then the sacculi from such cells should have been observed with a D-Cys-labelled old pole and a partially unlabelled new pole.…”

Section: Methodsmentioning

confidence: 99%

Patchiness of murein insertion into the sidewall of Escherichia coli

2003

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This paper extends, with computer techniques, the authors' previous work on the kinetics of pole wall and sidewall synthesis in Escherichia coli. These findings extend the conclusion that the nascent poles are made of entirely new material and that no new material is inserted into old poles. This requires re-evaluation of ideas in the literature about wall growth and cell division. Mechanisms of various types have been suggested for the growth of Gram-negative rod-shaped bacteria and these will also require major re-evaluation because of the finding, reported here, that the sidewall is made in several modes: patches of new murein, bands of new material largely going circumferentially around the cell, and areas of the sidewall that are enlarged by an intimate and regular admixture of new with the old muropeptides.

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“…To create filamentous cells with a low surface density of flagella and a length that was similar to that of swarming cells, we treated vegetative P. mirabilis cells with aztreonam, an antibiotic that specifically inhibits penicillin-binding protein 3 and arrests bacterial cell division (34). The elongated vegetative cells we isolated and studied had a mean length of 19.4 Ϯ 5.7 m; 99% of the cell population had a length of Ն10 m, which made it consistent with the length of P. mirabilis swarm cells in our studies (see Fig.…”

Section: Isolating Populations Of Different Cell Morphologiesmentioning

confidence: 99%

Flagellum Density Regulates Proteus mirabilis Swarmer Cell Motility in Viscous Environments

et al. 2013

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cProteus mirabilis is an opportunistic pathogen that is frequently associated with urinary tract infections. In the lab, P. mirabilis cells become long and multinucleate and increase their number of flagella as they colonize agar surfaces during swarming. Swarming has been implicated in pathogenesis; however, it is unclear how energetically costly changes in P. mirabilis cell morphology translate into an advantage for adapting to environmental changes. We investigated two morphological changes that occur during swarming-increases in cell length and flagellum density-and discovered that an increase in the surface density of flagella enabled cells to translate rapidly through fluids of increasing viscosity; in contrast, cell length had a small effect on motility. We found that swarm cells had a surface density of flagella that was ϳ5 times larger than that of vegetative cells and were motile in fluids with a viscosity that inhibits vegetative cell motility. To test the relationship between flagellum density and velocity, we overexpressed FlhD 4 C 2 , the master regulator of the flagellar operon, in vegetative cells of P. mirabilis and found that increased flagellum density produced an increase in cell velocity. Our results establish a relationship between P. mirabilis flagellum density and cell motility in viscous environments that may be relevant to its adaptation during the infection of mammalian urinary tracts and movement in contact with indwelling catheters. Proteus mirabilis is a Gram-negative rod-shaped gammaproteobacterium that is commonly associated with urinary tract infections (1) and the biofouling of catheters (2-4). P. mirabilis may also be present in the human gut microflora (5) and is correlated with the incidence of colitis (6, 7). Broth-grown vegetative cells of P. mirabilis are characteristically ϳ2 m long and have a peritrichous distribution of ϳ4 to 10 flagella. The flagella form a bundle that performs work on the surrounding fluid and propels cells forward via a mechanism that is similar to the motility system of Escherichia coli (8, 9).Broth-grown vegetative cells of P. mirabilis in contact with the surface of agar gels infused with nutrients change their morphology, become "swarmers," and colonize the surface by coordinating the movement of large groups of cells (i.e., "swarming") (see Fig. 1A). P. mirabilis swarm colonies exhibit a terraced pattern of concentric rings (see Fig. S1 in the supplemental material) (10). These rings are produced by alternating phases of consolidation, during which the colony does not expand and cells are dedifferentiated into a vegetative cell-like morphology, and swarming, during which cells are motile and differentiated (11). Motility occurs predominantly at the swarm front and decreases with increasing distance from the front; cells near the center of the swarm are nonmotile. Swarming has several characteristics, including the following: (i) the inhibition of cell division to produce long (10-to 70-m) multinucleate cells, (ii) an increase in the surface dens...

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Discovery and Development of the Monobactams

Cited by 74 publications

References 25 publications

AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli

AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli

Patchiness of murein insertion into the sidewall of Escherichia coli

Flagellum Density Regulates Proteus mirabilis Swarmer Cell Motility in Viscous Environments

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