Plasmid-Mediated Rifampin Resistance Encoded by an
 
 arr-2
 -Like Gene Cassette in
 Klebsiella pneumoniae
 Producing an ACC-1 Class C β-Lactamase

Arlet, Guillaume; Nadjar, David; Herrmann, Jean-Louis; Donay, Jean-Luc; Rouveau, M.; Lagrange, Philippe; Philippon, A.

doi:10.1128/aac.45.10.2971-2972.2001

Cited by 29 publications

(26 citation statements)

References 9 publications

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“…The resistance in these isolates is normally conferred by missense mutations in the RNA polymerase gene rpoB (45). However, a plasmid-mediated rifampin resistance gene was found recently in Klebsiella pneumoniae (2). Preliminary tests on the function of ORF10 did not show observable differences in rifampin resistance between the parental strain QM B1551 and the plasmidless strain PV361.…”

Section: Resultsmentioning

confidence: 99%

Molecular Characterization of Plasmid pBM300 from Bacillus megaterium QM B1551

Kunnimalaiyaan

Vary

2005

Appl Environ Microbiol

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Strain QM B1551 of Bacillus megaterium contains seven compatible plasmids: two small rolling circle plasmids and five theta-replicating plasmids with cross-hybridizing replicons. To expand our understanding of these plasmids, the replicon region (6.7 kb) from pBM300 was cloned, sequenced, and functionally characterized. Sequence analysis showed that the replication protein (RepM300) was highly homologous to two other plasmid Rep proteins of the same strain but to no other known proteins. Furthermore, the location of the replication origin was within the RepM300 coding region, and the origin contained three 12-base direct repeats. Deletion analysis of the replicon confirmed the role of the Rep protein and showed that open reading frame 2 (ORF2) was required for stability. However, the protein encoded by ORF2 is entirely different from the replicon stability proteins encoded by the other two replicons. The entire plasmid was isolated from the plasmid array by integrating a spectinomycin resistance gene and transforming a plasmidless strain, PV361. Complete sequencing showed that pBM300 was 26,300 bp long, had a G؉C content of 35.2%, and contained 20 ORFs, two of which encoded proteins that had no similarity to other proteins in the database. The proteins encoded by the plasmid ORFs had similarity to proteins for mobilization and transfer, an integrase, a rifampin resistance protein, a cell wall hydrolase, glutathione synthase, and a biotin carboxylase. The similarities were to several gram-positive genera and a few gram-negative genera and archaea. oriT and ssoT-like regions were detected near two mob genes. These results suggest that pBM300 is a mobilizable hybrid plasmid that confers increased metabolic and germination ability on its host. Its replicon also helps define a new plasmid family.

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Section: Resultsmentioning

confidence: 99%

Molecular Characterization of Plasmid pBM300 from Bacillus megaterium QM B1551

Kunnimalaiyaan

Vary

2005

Appl Environ Microbiol

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“…AJ277027 [4]). It differs from another arr-2 cassette reported to occur in P. aeruginosa and E. coli by one base (A3G), translating to one amino acid change (Lys983Arg) (34,57).…”

Section: Class 1 Integron Bearing the Bla Imp-4 -Qacg2-aaca4-catb3mentioning

confidence: 99%

Epidemiology of Rifampin ADP-Ribosyltransferase ( arr-2 ) and Metallo-β-Lactamase ( bla _IMP-4 ) Gene Cassettes in Class 1 Integrons in Acinetobacter Strains Isolated from Blood Cultures in 1997 to 2000

Houang

Chu

et al. 2003

Antimicrob Agents Chemother

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We characterized two new gene cassettes in an Acinetobacter isolate: one harbored the metallo-␤-lactamase (IMP-4) gene bla IMP-4 , the other harbored the rifampin ADP-ribosyltransferase (ARR-2) gene arr-2, and both arrayed with the aminoglycoside acetyltransferase [AAC(6)-Ib 7 ] gene cassette aacA4 in two separate class 1 integrons. The epidemiology of these gene cassettes in isolates from blood cultures obtained from 1997 to 2000 was studied. Isolates bearing either the bla IMP-4 or the arr-2 gene cassette or both represented 17.5% (10 of 57) of isolates in 1997, 16.1% (10 of 62) in 1998, 2.5% (1 of 40) in 1999, and 0% (0 of 58) in 2000. These two gene cassettes, probably borne on two separate integrons, were found in at least three genomic DNA groups, with evidence of clonal dissemination in the intensive care unit during 1997 to 1998. Seventeen of the 52 Acinetobacter baumannii (genomic DNA group 2) isolates from 1997 to 2000 harbored intI1, but only one was positive for these gene cassettes, whereas 20 of the 21 intI1-positive isolates of all other genomic DNA groups were positive for either or both of them. Reduced susceptibility to imipenem and rifampin was seen only in isolates harboring the bla IMP-4 and arr-2 cassettes, respectively. The aminoglycoside phosphotransferase [APH(3)-VIa] gene aph(3)-VIa was detected in all 21 isolates for which the MIC of amikacin was >8 g/ml, with or without aacA4, whereas aacA4 alone was found in isolates for which the MIC of amikacin was 0.5 to 2 g/ml. Significant differences between the 17 intI1-positive and 47 intI1-negative isolates belonging to genomic DNA group 3 from 1997 to 1998 in the MICs of amikacin, gentamicin, imipenem, sulfamethoxazole, and ceftazidime were observed (Mann-Whitney test, P < 0.001 to 0.01).In the past decade, there has been an explosion of interest in the integron, a genetic element which facilitates gene dissemination among bacteria of different species and perhaps genera, thus establishing the possibility of a wide dispersal of antimicrobial resistance. These genetic elements are marked by the presence of two conserved regions between which gene cassettes are integrated at a recombination site known as attI. The 5Ј-conserved region of an integron contains an integrase gene, intI, and a promoter (P c ) which drives the expression of any integrated gene cassettes. Individual gene cassettes, existing in a free circularized form when not integrated, are comprised of an open reading frame (ORF) and a 59-base element (59-be) at the 3Ј end. The 59-be is a family of recombination sites that act as substrates to integrase-mediated recombination (43). To date, over 70 resistance cassettes have been described (32, 45). According to the 3Ј-conserved sequence (3Ј-CS), integrons are divided into three classes. The majority of the resistance cassette-bearing integrons belong to class 1, and these carry, at the 3Ј-CS, the truncated quaternary ammonium compound resistance gene qacE⌬1, the sul1 sulfonamide resistance gene, and orf5, of unknown function (20).A...

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“…Arr-ms is a small enzyme (Ϸ16 kDa) with no sequence similarity to known protein ADPribosyltransferases such as ART, PARP, and bacterial toxins (6,29). Paradoxically, a homologue of Arr, Arr-2 (55% identical with Arr-ms), also is present in several transposons and integrons found in Gram-negative pathogenic bacteria such as P. aeruginosa (30), Escherichia coli (31), Klebsiella pneumoniae (32), and Acinetobacter baumannii (33). This distribution of arr-2 in Gramnegative pathogens is unexpected because rifampin is not used to treat infections caused by these bacteria, and therefore the selective pressure for maintaining this resistance cassette would be predicted to be low unless the patient was receiving rifampin treatment for other infections and as a result this has selected for ''bystander'' resistance in Gram-negative bacteria.…”

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confidence: 99%

Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr

Baysarowich

Koteva

Hughes

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

164

196

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The rifamycin antibiotic rifampin is important for the treatment of tuberculosis and infections caused by multidrug-resistant Staphylococcus aureus. Recent iterations of the rifampin core structure have resulted in new drugs and drug candidates for the treatment of a much broader range of infectious diseases. This expanded use of rifamycin antibiotics has the potential to select for increased resistance. One poorly characterized mechanism of resistance is through Arr enzymes that catalyze ADP-ribosylation of rifamycins. We find that genes encoding predicted Arr enzymes are widely distributed in the genomes of pathogenic and nonpathogenic bacteria. Biochemical analysis of three representative Arr enzymes from environmental and pathogenic bacterial sources shows that these have equally efficient drug resistance capacity in vitro and in vivo. The 3D structure of one of these orthologues from Mycobacterium smegmatis was determined and reveals structural homology with ADP-ribosyltransferases important in eukaryotic biology, including poly(ADP-ribose) polymerases (PARPs) and bacterial toxins, despite no significant amino acid sequence homology with these proteins. This work highlights the extent of the rifamycin resistome in microbial genera with the potential to negatively impact the expanded use of this class of antibiotic.crystallography ͉ resistome ͉ rifampin ͉ ribosyltransferase

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Plasmid-Mediated Rifampin Resistance Encoded by an arr-2 -Like Gene Cassette in Klebsiella pneumoniae Producing an ACC-1 Class C β-Lactamase

Cited by 29 publications

References 9 publications

Molecular Characterization of Plasmid pBM300 from Bacillus megaterium QM B1551

Molecular Characterization of Plasmid pBM300 from Bacillus megaterium QM B1551

Epidemiology of Rifampin ADP-Ribosyltransferase ( arr-2 ) and Metallo-β-Lactamase ( bla _IMP-4 ) Gene Cassettes in Class 1 Integrons in Acinetobacter Strains Isolated from Blood Cultures in 1997 to 2000

Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr

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Plasmid-Mediated Rifampin Resistance Encoded by an arr-2 -Like Gene Cassette in Klebsiella pneumoniae Producing an ACC-1 Class C β-Lactamase

Cited by 29 publications

References 9 publications

Molecular Characterization of Plasmid pBM300 from Bacillus megaterium QM B1551

Molecular Characterization of Plasmid pBM300 from Bacillus megaterium QM B1551

Epidemiology of Rifampin ADP-Ribosyltransferase ( arr-2 ) and Metallo-β-Lactamase ( bla IMP-4 ) Gene Cassettes in Class 1 Integrons in Acinetobacter Strains Isolated from Blood Cultures in 1997 to 2000

Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr

Contact Info

Product

Resources

About

Epidemiology of Rifampin ADP-Ribosyltransferase ( arr-2 ) and Metallo-β-Lactamase ( bla _IMP-4 ) Gene Cassettes in Class 1 Integrons in Acinetobacter Strains Isolated from Blood Cultures in 1997 to 2000