High-Level Resistance to Aminoglycosides due to 16S rRNA Methylation in Enterobacteriaceae Isolates

2019 ◽  
Vol 25 (9) ◽  
pp. 1261-1265 ◽  
Author(s):  
Fatemeh Yeganeh Sefidan ◽  
Yalda Mohammadzadeh-Asl ◽  
Reza Ghotaslou
Keyword(s):  
16S Rrna ◽  
High Level ◽  
Level Resistance ◽  
Rrna Methylation

scholarly journals ArmA Methyltransferase in a Monophasic Salmonella enterica Isolate from Food

2011 ◽  
Vol 55 (11) ◽  
pp. 5262-5266 ◽  
Author(s):  
Sophie A. Granier ◽  
Laura Hidalgo ◽  
Alvaro San Millan ◽  
Jose Antonio Escudero ◽  
Belen Gutierrez ◽  
...  
Keyword(s):  
16S Rrna ◽  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Broad Host Range ◽  
En Bloc ◽  
Content Type ◽  
Route Of Transmission ◽  
Amoxicillin Clavulanate ◽  
High Level ◽  
Level Resistance

ABSTRACTThe 16S rRNA methyltransferase ArmA is a worldwide emerging determinant that confers high-level resistance to most clinically relevant aminoglycosides. We report here the identification and characterization of a multidrug-resistantSalmonella entericasubspecies I.4,12:i:− isolate recovered from chicken meat sampled in a supermarket on February 2009 in La Reunion, a French island in the Indian Ocean. Susceptibility testing showed an unusually high-level resistance to gentamicin, as well as to ampicillin, expanded-spectrum cephalosporins and amoxicillin-clavulanate. Molecular analysis of the 16S rRNA methyltransferases revealed presence of thearmAgene, together withblaTEM-1,blaCMY-2, andblaCTX-M-3. All of these genes could be transferreden blocthrough conjugation intoEscherichia coliat a frequency of 10−5CFU/donor. Replicon typing and S1 pulsed-field gel electrophoresis revealed that thearmAgene was borne on an ∼150-kb broad-host-range IncP plasmid, pB1010. To elucidate howarmAhad integrated in pB1010, a PCR mapping strategy was developed for Tn1548, the genetic platform forarmA.The gene was embedded in a Tn1548-like structure, albeit with a deletion of the macrolide resistance genes, and an IS26was inserted within themelgene. To our knowledge, this is the first report of ArmA methyltransferase in food, showing a novel route of transmission for this resistance determinant. Further surveillance in food-borne bacteria will be crucial to determine the role of food in the spread of 16S rRNA methyltransferase genes worldwide.

scholarly journals Inactivation of KsgA, a 16S rRNA Methyltransferase, Causes Vigorous Emergence of Mutants with High-Level Kasugamycin Resistance

2008 ◽  
Vol 53 (1) ◽  
pp. 193-201 ◽  
Author(s):  
Kozo Ochi ◽  
Ji-Yun Kim ◽  
Yukinori Tanaka ◽  
Guojun Wang ◽  
Kenta Masuda ◽  
...  
Keyword(s):  
16S Rrna ◽  
High Frequency ◽  
Resistance Mutations ◽  
Gene Encoding ◽  
Adenosylmethionine Decarboxylase ◽  
Ribosomal Function ◽  
High Level ◽  
Antibiotic Resistance Mutations ◽  
Modest Level ◽  
Level Resistance

ABSTRACT The methyltransferases RsmG and KsgA methylate the nucleotides G535 (RsmG) and A1518 and A1519 (KsgA) in 16S rRNA, and inactivation of the proteins by introducing mutations results in acquisition of low-level resistance to streptomycin and kasugamycin, respectively. In a Bacillus subtilis strain harboring a single rrn operon (rrnO), we found that spontaneous ksgA mutations conferring a modest level of resistance to kasugamycin occur at a high frequency of 10−6. More importantly, we also found that once cells acquire the ksgA mutations, they produce high-level kasugamycin resistance at an extraordinarily high frequency (100-fold greater frequency than that observed in the ksgA + strain), a phenomenon previously reported for rsmG mutants. This was not the case for other antibiotic resistance mutations (Tspr and Rifr), indicating that the high frequency of emergence of a mutation for high-level kasugamycin resistance in the genetic background of ksgA is not due simply to increased persistence of the ksgA strain. Comparative genome sequencing showed that a mutation in the speD gene encoding S-adenosylmethionine decarboxylase is responsible for the observed high-level kasugamycin resistance. ksgA speD double mutants showed a markedly reduced level of intracellular spermidine, underlying the mechanism of high-level resistance. A growth competition assay indicated that, unlike rsmG mutation, the ksgA mutation is disadvantageous for overall growth fitness. This study clarified the similarities and differences between ksgA mutation and rsmG mutation, both of which share a common characteristic—failure to methylate the bases of 16S rRNA. Coexistence of the ksgA mutation and the rsmG mutation allowed cell viability. We propose that the ksgA mutation, together with the rsmG mutation, may provide a novel clue to uncover a still-unknown mechanism of mutation and ribosomal function.

scholarly journals Outbreak Caused by NDM-1- and RmtB-Producing Escherichia coli in Bulgaria

2014 ◽  
Vol 58 (4) ◽  
pp. 2472-2474 ◽  
Author(s):  
Laurent Poirel ◽  
Encho Savov ◽  
Arzu Nazli ◽  
Angelina Trifonova ◽  
Iva Todorova ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
16S Rrna ◽  
Sequence Type ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
The World ◽  
High Level ◽  
16S Rrna Methylase ◽  
Level Resistance

ABSTRACTTwelve consecutive carbapenem-resistantEscherichia coliisolates were recovered from patients (infection or colonization) hospitalized between March and September 2012 in different units at a hospital in Bulgaria. They all produced the carbapenemase NDM-1 and the extended-spectrum-β-lactamase CTX-M-15, together with the 16S rRNA methylase RmtB, conferring high-level resistance to all aminoglycosides. All those isolates were clonally related and belonged to the same sequence type, ST101. In addition to being the first to identify NDM-producing isolates in Bulgaria, this is the very first study reporting an outbreak of NDM-1-producingE. coliin the world.

scholarly journals Plasmid-Mediated High-Level Resistance to Aminoglycosides in Enterobacteriaceae Due to 16S rRNA Methylation

2003 ◽  
Vol 47 (8) ◽  
pp. 2565-2571 ◽  
Author(s):  
Marc Galimand ◽  
Patrice Courvalin ◽  
Thierry Lambert
Keyword(s):  
16S Rrna ◽  
Multiple Antibiotic Resistance ◽  
Human Pathogens ◽  
Aminoglycoside Resistance ◽  
New Host ◽  
Gram Negative ◽  
Infection Resistance ◽  
New Gene ◽  
High Level ◽  
Level Resistance

ABSTRACT A self-transferable plasmid of ca. 80 kb, pIP1204, conferred multiple-antibiotic resistance to Klebsiella pneumoniae BM4536, which was isolated from a urinary tract infection. Resistance to β-lactams was due to the bla TEM1 and bla CTX-M genes, resistance to trimethroprim was due to the dhfrXII gene, resistance to sulfonamides was due to the sul1 gene, resistance to streptomycin-spectinomycin was due to the ant3"9 gene, and resistance to nearly all remaining aminoglycosides was due to the aac3-II gene and a new gene designated armA (aminoglycoside resistance methylase). The cloning of armA into a plasmid in Escherichia coli conferred to the new host high-level resistance to 4,6-disubstituted deoxystreptamines and fortimicin. The deduced sequence of ArmA displayed from 37 to 47% similarity to those of 16S rRNA m7G methyltransferases from various actinomycetes, which confer resistance to aminoglycoside-producing strains. However, the low guanine-plus-cytosine content of armA (30%) does not favor an actinomycete origin for the gene. It therefore appears that posttranscriptional modification of 16S rRNA can confer high-level broad-range resistance to aminoglycosides in gram-negative human pathogens.

scholarly journals Plasmid-Mediated 16S rRNA Methylases in Aminoglycoside-Resistant Enterobacteriaceae Isolates in Shanghai, China

2008 ◽  
Vol 53 (1) ◽  
pp. 271-272 ◽  
Author(s):  
Qiong Wu ◽  
Yibo Zhang ◽  
Lizhong Han ◽  
Jingyong Sun ◽  
Yuxing Ni
Keyword(s):  
Escherichia Coli ◽  
16S Rrna ◽  
Klebsiella Pneumoniae ◽  
Gel Electrophoresis ◽  
Enterobacter Cloacae ◽  
Pulsed Field Gel Electrophoresis ◽  
Pulsed Field ◽  
High Level ◽  
Level Resistance

ABSTRACT High-level resistance to aminoglycosides produced by 16S rRNA methylases in Enterobacteriaceae isolates was investigated. The prevalences of armA in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were 0.6%, 3.0%, and 10%, respectively. rmtB was more prevalent than armA. Pulsed-field gel electrophoresis patterns indicated that armA and rmtB have spread horizontally and clonally.

scholarly journals Coproduction of Novel 16S rRNA Methylase RmtD and Metallo-β-Lactamase SPM-1 in a Panresistant Pseudomonas aeruginosa Isolate from Brazil

2006 ◽  
Vol 51 (3) ◽  
pp. 852-856 ◽  
Author(s):  
Yohei Doi ◽  
Doroti de Oliveira Garcia ◽  
Jennifer Adams ◽  
David L. Paterson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
16S Rrna ◽  
Moderate Degree ◽  
Aminoglycoside Resistance ◽  
Disk Diffusion Test ◽  
Serious Infections ◽  
High Level ◽  
16S Rrna Methylase ◽  
Cloning Experiment ◽  
Level Resistance

ABSTRACT Serious infections with Pseudomonas aeruginosa are frequently treated with the combination of a β-lactam antimicrobial and an aminoglycoside. P. aeruginosa strain PA0905 was isolated in 2005 from an inpatient in Brazil. It showed a panresistant phenotype that included resistance to β-lactams, aminoglycosides, and fluoroquinolones. The β-lactam resistance was conferred by the production of the metallo-β-lactamase SPM-1. No inhibitory zone was observed when a disk diffusion test was performed with the semisynthetic aminoglycoside arbekacin, raising suspicion of 16S rRNA methylase production. A cloning experiment subsequently revealed the presence of a novel 16S rRNA methylase, RmtD, which accounted for the high-level resistance to all 4,6-disubstituted deoxystreptamine aminoglycosides, such as amikacin, tobramycin, and gentamicin. RmtD shared a moderate degree of identity with RmtA, another 16S rRNA methylase that was initially reported to occur in P. aeruginosa in Japan in 2003. This is the first identification of aminoglycoside resistance mediated by a 16S rRNA methylase in South America. This is also the first report to document coproduction of a metallo-β-lactamase and a 16S rRNA methylase, a combination that would severely compromise therapeutic options for the infected patients.

scholarly journals Detection of Methyltransferases Conferring High-Level Resistance to Aminoglycosides in Enterobacteriaceae from Europe, North America, and Latin America

2008 ◽  
Vol 52 (5) ◽  
pp. 1843-1845 ◽  
Author(s):  
Thomas R. Fritsche ◽  
Mariana Castanheira ◽  
George H. Miller ◽  
Ronald N. Jones ◽  
Eliana S. Armstrong
Keyword(s):  
Latin America ◽  
North America ◽  
16S Rrna ◽  
Novel Species ◽  
Careful Monitoring ◽  
Aminoglycoside Resistance ◽  
Molecular Studies ◽  
Surveillance Programs ◽  
High Level ◽  
Level Resistance

ABSTRACT The alteration of ribosomal targets by recently described 16S rRNA methyltransferases confers resistance to most aminoglycosides, including arbekacin. Enterobacteriaceae and nonfermentative bacilli acquired through global surveillance programs were screened for the presence of these enzymes on the basis of phenotypes that were resistant to nine tested aminoglycosides. Subsequent molecular studies determined that 20 of 21 (95.2%) methyltransferase-positive isolates consisted of novel species records or geographic occurrences (North America [armA and rmtB], Latin America [rmtD], and Europe [armA]; rmtA, rmtC, and npmA were not detected). The global emergence of high-level aminoglycoside resistance has become a rapidly changing event requiring careful monitoring.

scholarly journals The Pathogen-Derived Aminoglycoside Resistance 16S rRNA Methyltransferase NpmA Possesses Dual m1A1408/m1G1408 Specificity

2015 ◽  
Vol 59 (12) ◽  
pp. 7862-7865 ◽  
Author(s):  
Natalia Zelinskaya ◽  
Marta A. Witek ◽  
Graeme L. Conn
Keyword(s):  
16S Rrna ◽  
Chemical Modification ◽  
Biological Significance ◽  
Aminoglycoside Antibiotics ◽  
Aminoglycoside Resistance ◽  
Resistance Determinants ◽  
High Level ◽  
Level Resistance

ABSTRACTChemical modification of 16S rRNA can confer exceptionally high-level resistance to a diverse set of aminoglycoside antibiotics. Here, we show that the pathogen-derived enzyme NpmA possesses dual m1A1408/m1G1408 activity, an unexpected property apparently unique among the known aminoglycoside resistance 16S rRNA (m1A1408) methyltransferases. Although the biological significance of this activity remains to be determined, such mechanistic variation in enzymes acquired by pathogens has significant implications for development of inhibitors of these emerging resistance determinants.

scholarly journals Aminoglycoside Resistance with Homogeneous and Heterogeneous Populations of Antibiotic-Resistant Ribosomes

2001 ◽  
Vol 45 (9) ◽  
pp. 2414-2419 ◽  
Author(s):  
Michael I. Recht ◽  
Joseph D. Puglisi
Keyword(s):  
16S Rrna ◽  
Small Subunit ◽  
Aminoglycoside Resistance ◽  
Antibiotic Resistant ◽  
Partial Dominance ◽  
E Coli ◽  
Bacterial Ribosome ◽  
High Level ◽  
Decoding Region ◽  
Level Resistance

ABSTRACT Aminoglycosides bind to rRNA in the small subunit of the bacterial ribosome. Mutations in the decoding region of 16S rRNA confer resistance to specific subsets of aminoglycoside antibiotics. The two major classes of 2-deoxystreptamine aminoglycosides are the 4,5- and the 4,6-disubstituted antibiotics. Antibiotics of the 4,5-disubstituted class include neomycin, paromomycin, and ribostamycin. Gentamicins and kanamycins belong to the 4,6-disubstituted class of aminoglycosides. Structural studies indicated the potential importance of position 1406 (Escherichia coli numbering) in the binding of ring III of the 4,6-disubstituted class of aminoglycosides to 16S rRNA. We have introduced a U1406-to-A mutation in a plasmid-encoded copy of E. coli 16S rRNA which has been expressed either in a mixture with wild-type ribosomes or in a strain in which all rRNA is transcribed from the plasmid-encoded rrn operon. High-level resistance to many of the 4,6-disubstituted aminoglycosides is observed only when all the rRNA contains the U1406-to-A mutation. In contrast to the partial dominance of resistance observed with other mutations in the decoding region, there is a dominance of sensitivity with the 1406A mutation. Chemical footprinting experiments indicate that resistance arises from a reduced affinity of the antibiotic for the rRNA target. These results demonstrate that although position 1406 is an important determinant in the binding and action of the 4,6-disubstituted aminoglycosides, other rRNA mutations that perturb the binding of ring I of both classes of 2-deoxystreptamine aminoglycosides confer higher levels of resistance as well as a partial dominance of resistance.

Sign in / Sign up

Export Citation Format

Share Document