Ribosomal Mutations in
            <i>Streptococcus pneumoniae</i>
            Clinical Isolates

Pihlajamäki, Marja; Kataja, Janne; Seppälä, Helena; Elliot, John; Leinonen, Maija; Huovinen, Pentti; Jalava, Jari

doi:10.1128/aac.46.3.654-658.2002

Cited by 60 publications

(71 citation statements)

References 33 publications

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“…Recently, other mechanisms of macrolide resistance (amino acid substitutions in domain V of 23S rRNA or mutations of L4 and L22 proteins) in vitro (3,20) and in clinical isolates (2,15,21) have been reported often. Kaieda et al reported an S. pneumoniae strain with an ermB mutation that showed in vitro constitutive macrolide resistance (S. Kaieda, S., H. Yano, N. Okitsu, Y. Hosaka, R. Okamoto, H. Takahashi, and M. Inoue, Abstr.…”

Section: Discussionmentioning

confidence: 99%

Characterization of ermB Gene Transposition by Tn 1545 and Tn 917 in Macrolide-Resistant Streptococcus pneumoniae Isolates

et al. 2005

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In Streptococcus pneumoniae, the ermB gene is carried by transposons, such as Tn917 and Tn1545. This study investigated the relationship between macrolide resistance and the presence of the ermB gene on Tn917 or Tn1545 in 84 Japanese pneumococcal isolates. Macrolide-resistant strains were classified into two groups as follows. Group 1 (19 strains) showed a tendency to high resistance to erythromycin (MIC at which 50% of isolates are inhibited, 4 mg/liter; MIC at which 90% of isolates are inhibited [MIC 90 ], 128 mg/liter) but susceptibility to rokitamycin (MIC 90 , 1 mg/liter), with the ermB gene located on Tn1545. Group 2 (65 strains) showed a tendency to high resistance to both antibiotics (MIC 90 s for both erythromycin and rokitamycin, >128 mg/liter), with the ermB gene located on Tn917. There were no strains with constitutive macrolide resistance in either group. All of the strains in group 2 had a deletion in the promoter region of ermB and an insertion of the TAAA motif in the leader peptide. The results of pulsed-field gel electrophoresis and serogrouping showed that Tn1545 spread clonally while Tn917 spread both horizontally and clonally. In conclusion, in Japanese macrolide-resistant S. pneumoniae isolates, the ermB gene is carried and spread primarily by Tn917.

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Section: Discussionmentioning

confidence: 99%

Characterization of ermB Gene Transposition by Tn 1545 and Tn 917 in Macrolide-Resistant Streptococcus pneumoniae Isolates

et al. 2005

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“…These mutations can confer resistance to MLS B antibacterials and, in some cases, to ketolides (1,11). Ribosomal mutations have also been found in MLS B -resistant clinical isolates, although reports are rare at present (2,9,10).…”

mentioning

confidence: 99%

In Vitro Activities of Telithromycin, Linezolid, and Quinupristin-Dalfopristin against Streptococcus pneumoniae with Macrolide Resistance Due to Ribosomal Mutations

Farrell

Morrissey

Bakker

et al. 2004

Antimicrob Agents Chemother

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To date, 86 of 7,746 macrolide-resistant Streptococcus pneumoniae isolates from 1999 to 2002 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance studies were negative for methylase and efflux mechanisms. Mutations in 23S rRNA or the genes encoding riboprotein L4 or L22 were found in 77 of 86 isolates. Six isolates were resistant to quinupristin-dalfopristin and two were resistant to linezolid, while telithromycin demonstrated good activities against all isolates.Macrolide, lincosamide, and streptogramin B (MLS B ) resistance in Streptococcus pneumoniae occurs predominantly by modification of the drug binding site and/or by drug efflux. Drug efflux is encoded by the mef(A) gene, while target modification is usually the result of methylation of the 23S rRNA, mostly by the product of the erm(B) gene and rarely by the erm(A) subclass erm(TR) gene. In vitro studies have demonstrated that target modification can also be achieved by mutations in domains II and V of 23S rRNA (in one to four of the four copies of this gene present in S. pneumoniae) and in the genes encoding riboproteins L4 and L22 (1, 11). These mutations can confer resistance to MLS B antibacterials and, in some cases, to ketolides (1, 11). Ribosomal mutations have also been found in MLS B -resistant clinical isolates, although reports are rare at present (2, 9, 10).PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, multicenter surveillance study of antibacterial resistance among respiratory tract pathogens from numerous countries worldwide. PROTEKT US is a sister study involving the United States only and began in 2000. All macrolide-resistant S. pneumoniae strains isolated during year 1 of the PROTEKT study (1999 to 2000) were screened for the common efflux and methylase genes associated with macrolide resistance to determine the global distributions of these mechanisms. Of 1,043 macrolide-resistant isolates screened, 16 (1.5%) isolates repeatedly tested negative for the erm and mef genes, while the remaining isolates were resistant to macrolides (4, 5). All isolates were found to harbor ribosomal mutations, most commonly A2059G (12 isolates) (4).(Preliminary data were presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chi (32.9%) were macrolide resistant; 86 (0.37%) macrolide-resistant isolates (including the 16 isolates reported previously) were negative for methylase and efflux mechanisms. The ribosomal mutations associated with macrolide resistance in these isolates were determined in this study. Before the isolates were sequenced for ribosomal mutations, macrolide resistance was confirmed by repeating the MIC determinations and comparing the MIC data with the initial results. Detection of L4 and L22 riboprotein and 23S rRNA gene mutations was performed as described previously (3). Briefly, the complete L4 and L22 operons and all four 23S rRNA operons were sequenced.

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“…Type B phenotype mutants had a A2058G mutation in 5 alleles, while Type C mutants were homozygous with all 6 ribosomal alleles having a A2062C mutation. A2058G and C2611G mutations are frequently detected in clinical isolates of S. pneumoniae (Vester & Douthwaite, 2001;Canu et al, 2002;Pihlajamaki et al, 2002). On the other hand, there is one report on a A2062C mutation (Type C phenotype in ST113) resulting in resistance to 16-membered macrolides (Tyl, Spm) and streptogramins while retaining sensitivity to the 14-membered lactone Erm (Depardieu & Courvalin, 2001 …”

Section: Detection Of Mutations In Domain V Of 23s Rrnamentioning

confidence: 99%

“…Several studies demonstrated that resistance to MLS antibiotics may also develop in streptococci and other bacteria by specific base substitutions in domain V of 23S rRNA (Vester & Douthwaite, 2001;Pihlajamaki et al, 2002;Jalava et al, 2004;Haanpera et al, 2005).…”

Section: Detection Of Mutations In Domain V Of 23s Rrnamentioning

confidence: 99%

“…In macrolide-specific efflux that is mediated by a membrane protein encoded by the mef (A) gene, resistance develops to 14-and 15-membered macrolides but not to 16-membered macrolides, lincosamides and streptogramins (Depardieu & Courvalin, 2001). Other known macrolide resistance mechanisms involve mutations in the ribosomal proteins L4 and L22, and also the 23S rRNA (Tait-Kamradt et al, 2000;Pihlajamaki et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of Resistance to Macrolide-Lincosamide-Streptogramin Antibiotics in Streptococcus thermophilus

Somkuti¹,

Renye²,

Steinberg³

2014

JFR

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Resistance to macrolide-lincosamide-streptogramin (MLS) group antibiotics in the dairy bacterium Streptococcus thermophilus (ST) is documented but the mechanism of resistance has not been elucidated. MIC values for erythromycin (Erm), azithromycin (Azm), tylosin (Tyl), spiramycin (Spm), pristinamycin (Prm) and virginiamycin S (Vir) were determined by the disk diffusion method. PCR products were obtained with primer pairs for the L4, L22 and 23S rDNA (domain V) genes. The sequencing results ruled out mutations in the L4 and L22 ribosomal proteins and the presence of rRNA methylase, efflux, and inactivating genes. However, sequencing of domain V in each of the six ribosomal alleles detected by EcoRI/I-CeuI digestion in ST mutants identified three types of mutations that led to MLS resistance. Type A mutants, induced by Erm, had high resistance to 14-and 15-membered ring macrolides (Erm, Azm) and streptogramin B antibiotics (Prm, Vir), moderate resistance to 16-membered ring macrolides (Tyl, Spm), but remained susceptible to lincomycin. In Type B mutants, also induced by Erm, resistance was high to Erm, Tyl and Spm, and moderate to lincomycin but sensitivity was retained to Prm. Type C mutants, induced by Prm, showed high resistance to 16-membered ring macrolides but remained sensitive to Erm, Azm and lincomycin. The three identifiable resistance patterns were apparently due to point mutations in domain V of the 23S rRNA gene, resulting in three phenotypes among resistant S. thermophilus isolates. Type A phenotype mutants had a C2611G mutation in five of the six ribosomal alleles, Type B phenotypes had a A2058G mutation in five alleles, and Type C variants had a A2062C mutation in all six alleles. Resistance to MLS antibiotics in S. thermophilus was inducible by 14-and 15-membered ring macrolides and streptogramin B type antibiotics but not by 16-membered ring macrolides or lincosamides.

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Ribosomal Mutations in Streptococcus pneumoniae Clinical Isolates

Cited by 60 publications

References 33 publications

Characterization of ermB Gene Transposition by Tn 1545 and Tn 917 in Macrolide-Resistant Streptococcus pneumoniae Isolates

Characterization of ermB Gene Transposition by Tn 1545 and Tn 917 in Macrolide-Resistant Streptococcus pneumoniae Isolates

In Vitro Activities of Telithromycin, Linezolid, and Quinupristin-Dalfopristin against Streptococcus pneumoniae with Macrolide Resistance Due to Ribosomal Mutations

Mechanism of Resistance to Macrolide-Lincosamide-Streptogramin Antibiotics in Streptococcus thermophilus

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