Four codons in the cat-86 leader define a chloramphenicol-sensitive ribosome stall sequence

Rogers, Elizabeth; Kim, U J; Ambulos, N P; Lovett, Paul S.

doi:10.1128/jb.172.1.110-115.1990

Cited by 29 publications

(29 citation statements)

References 28 publications

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“…3) (30). Further support for this idea was obtained when codon 3* of the upstream stall sequence of the tandem pair was changed from the (mutant) threonine codon to the (wildtype) lysine codon (Fig.…”

Section: Cat-86 Induction Is Due To Activation Of Mrna Translationmentioning

confidence: 55%

Translational attenuation as the regulator of inducible cat genes

Lovett

1990

J Bacteriol

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105

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Section: Cat-86 Induction Is Due To Activation Of Mrna Translationmentioning

confidence: 55%

Translational attenuation as the regulator of inducible cat genes

Lovett

1990

J Bacteriol

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105

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“…20,2007 MODULATION OF ANTIBIOTIC RESISTANCE GENE EXPRESSION 103 of interaction between the leader peptide and macrolides can occur. It seems that the leader peptide could be the selector of the site of ribosome stalling in leader mRNA by cis interference with translation, as previously demonstrated for the leader peptides controlling the inducible expression of cat genes (221). Considering the importance of the leader peptide sequence for specificity of induction, it is not surprising that certain mutations in this sequence lead to changes in the induction patterns.…”

Section: Inducible Expression Of Macrolide Resistancementioning

confidence: 87%

Modes and Modulations of Antibiotic Resistance Gene Expression

et al. 2007

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SUMMARY Since antibiotic resistance usually affords a gain of function, there is an associated biological cost resulting in a loss of fitness of the bacterial host. Considering that antibiotic resistance is most often only transiently advantageous to bacteria, an efficient and elegant way for them to escape the lethal action of drugs is the alteration of resistance gene expression. It appears that expression of bacterial resistance to antibiotics is frequently regulated, which indicates that modulation of gene expression probably reflects a good compromise between energy saving and adjustment to a rapidly evolving environment. Modulation of gene expression can occur at the transcriptional or translational level following mutations or the movement of mobile genetic elements and may involve induction by the antibiotic. In the latter case, the antibiotic can have a triple activity: as an antibacterial agent, as an inducer of resistance to itself, and as an inducer of the dissemination of resistance determinants. We will review certain mechanisms, all reversible, that bacteria have elaborated to achieve antibiotic resistance by the fine-tuning of the expression of genetic information.

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“…We initially observed that the codons which precede the leader stall site participate in selecting the site of stalling (22,25,26). This leader function now appears to be a direct result of the antiribosome activity of the product pentapeptide (12).…”

Section: Discussionmentioning

confidence: 99%

“…The anti-PT activity of the leader peptides is thought to play a critical role in the translation attenuation regulation of cat (1,8,11,13,17,26) and cmlA (6,33) by selecting the site of ribosome stalling (10,12). Thus, the in vivo synthesis of the inhibitor peptides coincides with the translation by a ribosome to the leader site at which ribosome stalling will activate downstream gene expression (1, 10).…”

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confidence: 99%

Properties of a pentapeptide inhibitor of peptidyltransferase that is essential for cat gene regulation by translation attenuation

Harrod

Rogers

et al. 1994

J Bacteriol

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Inducible chloramphenicol resistance genes cat and c*ml are regulated by translation attenuation. For both genes, the leader codons that must be translated to deliver a ribosome to the induction site specify a peptide that inhibits peptidyltransferase in vitro. The antipeptidyltransferase activity of the peptides is thought to select the site of ribosome stalling that is essential for Induction. Using variations of the cat-86 leader-encoded 5-mer peptide MVKTD, we demonstrate a correlation between the in vitro antipeptidyltransferase activity and the ability of the same peptide to support induction by chloramphenicol in vivo. MVKTD Peptide bond formation during translation is catalyzed by the ribosome-associated activity peptidyltransferase (PT) (21). PT is the target for several antibiotics including chloramphenicol and anisomycin (20). We have recently demonstrated that PT is also inhibited by the short peptides that are encoded by the leaders of attenuation regulated. chloramphenicol resistance genes (10, 12). The peptide inhibitors fall into two classes according to their sizes and specific inhibition. The leaders for inducible cat genes specify one class of PT-inhibitor peptides; the first five codons of the leaders encode 5-mer peptides that exhibit about 1/10 of the specific inhibition of chloramphenicol (10,12). The second class of inhibitor peptide consists of only one member, the eight-residue peptide that is encoded by the first eight codons of the cmlA leader (12). The cmlA 8-mer peptide is about one-half as inhibitory as chloramphenicol on SOS ribosomal subunits ofBacillus subtilis and is about fivefoldmore inhibitory than the cat leader peptides. Members of both classes of peptides may function similarly on the basis of their common footprints on 23S rRNA and the sensitivity of the inhibitory activity to competition by erythromycin (10). The mechanism of peptide inhibition of PT is probably not identical to that of chloramphenicol since the activities of chloramphenicol and the peptides are additive (10).The anti-PT activity of the leader peptides is thought to play a critical role in the translation attenuation regulation of cat (1,8,11,13,17,26) and cmlA (6,33) by selecting the site of ribosome stalling (10,12). Thus, the in vivo synthesis of the inhibitor peptides coincides with the translation by a ribosome to the leader site at which ribosome stalling will activate downstream gene expression (1, 10). Moreover, a missense mutation in the cat leader that prevents induction by chloram-* Corresponding author. Phone: (410) 455-2249. Fax: (410) 455-3875. phenicol causes an amino acid replacement in the 5-mer peptide that eliminates its anti-PT activity (12).In the present study we demonstrate that the in vitro inhibitory activity of a leader peptide correlates with the in vivo activity of the peptide in gene regulation. Examination of the peptide sensitivity of PT from several sources suggests that the target is a sequence or structure which is conserved in prokaryotic and eukaryotic ribosom...

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Four codons in the cat-86 leader define a chloramphenicol-sensitive ribosome stall sequence

Cited by 29 publications

References 28 publications

Translational attenuation as the regulator of inducible cat genes

Translational attenuation as the regulator of inducible cat genes

Modes and Modulations of Antibiotic Resistance Gene Expression

Properties of a pentapeptide inhibitor of peptidyltransferase that is essential for cat gene regulation by translation attenuation

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