Identification of Rifampicin Resistance Mutations in Escherichia coli, Including an Unusual Deletion Mutation

2017 ◽  
Vol 27 (6) ◽  
pp. 356-362 ◽  
Author(s):  
Eugene Y. Wu ◽  
Angela K. Hilliker
Keyword(s):  
Escherichia Coli ◽  
Rna Polymerase ◽  
Bacterial Infections ◽  
Deletion Mutant ◽  
Deletion Mutation ◽  
Rifampicin Resistance ◽  
Clinical Settings ◽  
Resistance Mutations ◽  
Gene Encoding ◽  
Β Chain

Rifampicin is an effective antibiotic against mycobacterial and other bacterial infections, but resistance readily emerges in laboratory and clinical settings. We screened <i>Escherichia coli</i> for rifampicin resistance and identified numerous mutations to the gene encoding the β-chain of RNA polymerase (<i>rpoB</i>), including an unusual 9-nucleotide deletion mutation. Structural modeling of the deletion mutant indicates locations of potential steric clashes with rifampicin. Sequence conservation in the region near the deletion mutation suggests a similar mutation may also confer resistance during the treatment of tuberculosis.

RNA polymerase rifampicin resistance mutations in Escherichia coli: Sequence changes and dominance

1983 ◽  
Vol 190 (2) ◽  
pp. 344-348 ◽  
Author(s):  
Yuri A. Ovchinnikov ◽  
Galina S. Monastyrskaya ◽  
Sergei O. Guriev ◽  
Nadezhda F. Kalinina ◽  
Eugene D. Sverdlov ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Rna Polymerase ◽  
Rifampicin Resistance ◽  
Resistance Mutations

scholarly journals Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages

2012 ◽  
Vol 57 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Migla Miskinyte ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Resistance Mutation ◽  
Fitness Cost ◽  
Resistance Mutations ◽  
Content Type ◽  
E Coli ◽  
Fitness Effects ◽  
K 12

ABSTRACTMutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in therpoB,rpsL, andgyrAgenes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits—growth rate and survival ability—of 12Escherichia coliK-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, allE. colistreptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival ofE. coliin the context of an infection.

An amber mutation in the gene encoding the beta' subunit of Escherichia coli RNA polymerase

1982 ◽  
Vol 152 (2) ◽  
pp. 736-746
Author(s):  
S P Ridley ◽  
M P Oeschger
Keyword(s):  
Escherichia Coli ◽  
High Temperature ◽  
Rna Polymerase ◽  
Coli Strain ◽  
Beta Subunit ◽  
Temperature Sensitive ◽  
Amber Mutation ◽  
Gene Encoding ◽  
Amber Suppressor

An Escherichia coli strain carrying an amber mutation (UAG) in rpoC, the gene encoding the beta prime subunit of RNA polymerase, was isolated after mutagenesis with nitrosoguanidine. The mutation was moved into an unmutagenized strain carrying the supD43,74 allele, which encodes a temperature-sensitive su1 amber suppressor, and sue alleles, which enhance the efficiency of the suppressor. In this background, beta prime is not synthesized at high temperature. Suppression of the mutation by the non-temperature-sensitive amber suppressor su1+ yields a protein which is functional at all temperatures examined (30, 37, and 42 degrees C).

scholarly journals Translational Regulation of the Escherichia coli Stress Factor RpoS: a Role for SsrA and Lon

2007 ◽  
Vol 189 (13) ◽  
pp. 4872-4879 ◽  
Author(s):  
Caroline Ranquet ◽  
Susan Gottesman
Keyword(s):  
Escherichia Coli ◽  
Low Temperature ◽  
Rna Polymerase ◽  
Transcription Initiation ◽  
Translational Regulation ◽  
Regulatory Rna ◽  
Gene Encoding ◽  
Ribosome Stalling ◽  
High Level ◽  
Sigma Subunit

ABSTRACT Escherichia coli cell viability during starvation is strongly dependent on the expression of the rpoS gene, encoding the RpoS sigma subunit of RNA polymerase. RpoS abundance has been reported to be regulated at many levels, including transcription initiation, translation, and protein stability. The regulatory RNA SsrA (or tmRNA) has both tRNA and mRNA activities, relieving ribosome stalling and cotranslationally tagging proteins. We report here that SsrA is needed for the correct high-level translation of RpoS. The ATP-dependent protease Lon was also found to negatively affect RpoS translation, but only at low temperature. We suggest that SsrA may indirectly improve RpoS translation by limiting ribosome stalling and depletion of some component of the translation machinery.

Plasmid-mediated ciprofloxacin resistance imparts a selective advantage on Escherichia coli ST131

2021 ◽  
Author(s):  
Minh-Duy Phan ◽  
Kate M. Peters ◽  
Laura Alvarez Fraga ◽  
Steven C. Wallis ◽  
Steven Hancock ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Selective Advantage ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
Gene Encoding ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Rapid Dissemination

Escherichia coli ST131 is a recently emerged antibiotic resistant clone responsible for high rates of urinary tract and bloodstream infections. Despite its global dominance, the precise mechanisms that have driven the rapid dissemination of ST131 remain unknown. Here, we show that the plasmid-associated resistance gene encoding the AAC(6’)-Ib-cr enzyme that inactivates the fluoroquinolone antibiotic ciprofloxacin is present in >70% of strains from the most rapidly expanding subgroup of multidrug resistant ST131. Using a series of genome-edited and plasmid-cured isogenic strains, we demonstrate that the aac(6’)-Ib-cr gene confers a selective advantage on ST131 in the presence of ciprofloxacin, even in strains containing chromosomal GyrA and ParC FQ-resistance mutations. Further, we identify a pattern of emerging carbapenem resistance in other common E. coli clones carrying both aac(6’)-Ib-cr and chromosomal FQ-resistance mutations, suggesting this dual resistance combination may also impart a selective advantage on these non-ST131 antibiotic resistant lineages.

scholarly journals Identification and characterization of pleiotropic high-persistence mutations in the beta subunit of the bacterial RNA polymerase

2020 ◽  
Author(s):  
Lev Ostrer ◽  
Yinduo Ji ◽  
Arkady Khodursky
Keyword(s):  
Antibiotic Resistance ◽  
Rna Polymerase ◽  
Low Frequency ◽  
Beta Subunit ◽  
Resistance Mutations ◽  
Chronic Infections ◽  
Gene Encoding ◽  
Bacterial Populations ◽  
Bacterial Rna ◽  
Transcriptional Changes

AbstractIndividual bacteria can escape killing by bactericidal antibiotics by becoming dormant. Such cells, also known as persisters, naturally occur in bacterial populations at a low frequency. Here we present the finding that antibiotic-resistance mutations in the rpoB gene, encoding the beta subunit of RNA polymerase, increase the frequency of persisters by orders of magnitude. Furthermore, we show that: i) the persistent state depends on the (p)ppGpp transcriptional program and not on (p)ppGpp itself; ii) the high persistence (hip) is associated with increased populational heterogeneity in transcription; iii) indole overproduction, caused by transcriptional changes in the hip mutants, explains 50-80% of the hip phenotype. We report that the analogous rpoB mutations occur frequently in clinical isolates of Acinetobacter baumannii, Mycobacterium tuberculosis and Staphylococcus aureus, and we demonstrate that one of those rpoB mutations causes high persistence in MRSA. We also show that the RpoB-associated hip phenotype can be reversed by inhibiting protein synthesis.ImportancePersistence is an inevitable consequence of antibiotic usage. Although persistence is not a genetically heritable trait, here we demonstrate for the first time that antibiotic resistance, which is heritable, can promote persistence formation. Our finding that resistance to one antibiotic, rifampicin, can boost persistence to other antibiotics, such as ciprofloxacin and ampicillin, may help explain why certain chronic infections are particularly recalcitrant to antibiotic therapies. Out results also emphasize the need to assess the effects of combination antibiotic therapies on persistence.

scholarly journals Escherichia coli mutations that prevent the action of the T4 unf/alc protein map in an RNA polymerase gene.

Genetics ◽  
1988 ◽  
Vol 118 (2) ◽  
pp. 173-180
Author(s):  
L Snyder ◽  
L Jorissen
Keyword(s):  
Escherichia Coli ◽  
Rna Polymerase ◽  
Bacteriophage T4 ◽  
Strong Support ◽  
Rpob Gene ◽  
Late Gene Expression ◽  
Gene Encoding ◽  
E Coli ◽  
A Subunit ◽  
Phage Production

Abstract Bacteriophage T4 has the substituted base hydroxymethylcytosine in its DNA and presumably shuts off host transcription by specifically blocking transcription of cytosine-containing DNA. When T4 incorporates cytosine into its own DNA, the shutoff mechanism is directed back at T4, blocking its late gene expression and phage production. Mutations which permit T4 multiplication with cytosine DNA should be in genes required for host shutoff. The only such mutations characterized thus far have been in the phage unf/alc gene. The product of this gene is also required for the unfolding of the host nucleoid after infection, hence its dual name unf/alc. As part of our investigation of the mechanism of action of unf/alc, we have isolated Escherichia coli mutants which propagate cytosine T4 even if the phage are genotypically alc+. These same E. coli mutants are delayed in the T4-induced unfolding of their nucleoid, lending strong support to the conclusion that blocking transcription and unfolding the host nucleoid are but different manifestations of the same activity. We have mapped two of the mutations, called paf mutations for prevent alc function. They both map at about 90 min, probably in the rpoB gene encoding a subunit of RNA polymerase. From the behavior of Paf mutants, we hypothesize that the unf/alc gene product of T4 interacts somehow with the host RNA polymerase to block transcription of cytosine DNA and unfold the host nucleoid.

scholarly journals Escherichia coli RNA Polymerase Is the Target of the Cyclopeptide Antibiotic Microcin J25

2001 ◽  
Vol 183 (15) ◽  
pp. 4543-4550 ◽  
Author(s):  
Mónica A. Delgado ◽  
Marı́a R. Rintoul ◽  
Ricardo N. Farı́as ◽  
Raúl A. Salomón
Keyword(s):  
Escherichia Coli ◽  
Rna Polymerase ◽  
Cyclic Peptide ◽  
Nucleotide Sequencing ◽  
Peptide Antibiotic ◽  
Amino Acid Residues ◽  
Gene Encoding ◽  
Microcin J25

ABSTRACT Escherichia coli microcin J25 (MccJ25) is a plasmid-encoded, cyclic peptide antibiotic consisting of 21 unmodified amino acid residues. It is primarily active on gram-negative bacteria related to the producer strain, inducing cell filamentation in an SOS-independent way. A mutation causing resistance to MccJ25 was isolated. Genetic analysis indicated that it resided in therpoC gene, encoding the β′ subunit of RNA polymerase, at 90 min on the E. coli genetic map. The mutation was genetically crossed on to a plasmid containing the wild-typerpoC gene. The presence of the recombinant plasmid conferred complete resistance to otherwise sensitive strains. Nucleotide sequencing of the plasmid-borne, mutant rpoCgene revealed a ACC (Thr)-to-ATC (Ile) change at codon 931, within homology block G, an evolutionarily conserved region in the large subunits of all RNA polymerases. MccJ25 decreased RNA synthesis both in vivo and in vitro. These results point to the RNA polymerase as the target of microcin action. We favor the possibility that the filamentous phenotype induced by MccJ25 results from impaired transcription of genes coding for cell division proteins. As far as we know, MccJ25 is the first peptide antibiotic shown to affect RNA polymerase.

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