PMID:1563353

Citation	Vinella, D, D'Ari, R, Jaffé, A and Bouloc, P (1992) Penicillin binding protein 2 is dispensable in Escherichia coli when ppGpp synthesis is induced.EMBO J. 11:1493-501
Abstract	Mecillinam, a beta-lactam antibiotic which specifically inactivates penicillin binding protein 2 (PBP2) in Escherichia coli, prevents lateral cell wall elongation, inducing spherical morphology and cell death. Two mecillinam resistant mutants, lov-1 and lovB, both able to dispense entirely with PBP2, are shown here to be affected in the aminoacyl-tRNA synthetase genes argS and alaS, respectively. Although the argS and alaS mutants grow slowly, we show that there is no correlation between mecillinam resistance and either growth rate or translation speed. A role of the ribosomes in mecillinam sensitivity, suggested by our earlier report that the lov-1 mutation is suppressed by certain rpsL(StrR) alleles affecting ribosomal protein S12, is supported by the present observation that a pseudo-streptomycin dependent mutant is mecillinam resistant in the presence of streptomycin. The argS and alaS mutants have high pools of the nucleotide ppGpp (effector of the stringent response) and the mecillinam resistance of both mutations is suppressed by a relA mutation, inactivating the ribosome-associated ppGpp synthetase and preventing ppGpp synthesis in response to aminoacyl-tRNA starvation. Furthermore, a ptacrelA' multicopy plasmid makes a wild type strain mecillinam resistant. The effect of ppGpp is probably mediated by RNA polymerase, since sublethal doses of the polymerase inhibitor rifampicin suppress mecillinam resistance in argS, alaS and ptacrelA'-bearing strains. We conclude that ppGpp regulates the transcription of a gene whose product is involved in mecillinam sensitivity, possibly as part of a chain of interacting elements which coordinate ribosomal activity with that of the PBPs.
Links	PubMed
Keywords	Alanine-tRNA Ligase; Alleles; Amdinocillin; Arginine-tRNA Ligase; Bacterial Proteins; Carrier Proteins; Cell Division; Chromosome Mapping; Drug Resistance, Microbial; Escherichia coli; Genes, Bacterial; Genotype; Guanosine Tetraphosphate; Hexosyltransferases; Multienzyme Complexes; Muramoylpentapeptide Carboxypeptidase; Mutation; Penicillin-Binding Proteins; Peptidyl Transferases; Restriction Mapping; Ribosomes; Rifampin
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Main Points of the Paper

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Materials and Methods Used

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Phenotype Annotations

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Phenotype of	Taxon Information	Genotype Information (if known)	Condition Information	OMP ID	OMP Term Name	ECO ID	ECO Term Name	Notes	Status
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: GC2700 NCBI Taxon ID: 83333	Genotype of Reference Strain: argS Genotype of Experimental Strain : argS201 in strain GC3700	Reference Condition:	OMP:0000276	increased resistance to antimicrobial compound			Resistance to Mecillinam (A B Lactam). See table 2.
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: GC2700 NCBI Taxon ID: 83333	Genotype of Reference Strain: argS Genotype of Experimental Strain : alaS21 in strain GC3702	Reference Condition:	OMP:0000276	increased resistance to antimicrobial compound			Resistance to Mecillinam (A B Lactam). See Table 2
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Notes

OMPID: Beta lactam antibiotic mecillinam has been made, needs approval and implementation.

ECOID: cell (solid) assays at 37C on rich medium, with antibiotic present at 50 micrograms/ml

References

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