Antimicrobial Susceptibility and Macrolide Resistance Inducibility of
 Streptococcus pneumoniae
 Carrying
 erm
 (A),
 erm
 (B), or
 mef
 (A)

Syrogiannopoulos, George A.; Grivea, Ioanna N.; Ednie, Lois M.; Bozdoğan, Bülent; Katopodis, George D.; Beratis, Nicholas G.; Davies, Todd A.; Appelbaum, Peter C.

doi:10.1128/aac.47.8.2699-2702.2003

Cited by 23 publications

(16 citation statements)

References 15 publications

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“…These findings demonstrated that the bicyclolide nucleus and aromatic side chain of modithromycin would contribute to the increased affinity for the dimethylated ribosome of streptococci, including telithromycin-resistant strains. Unlike the Erm phenotype in streptococci, except for ErmTR, the expression of the Erm phenotype can be determined to be inducible or constitutive in S. aureus by the inducibility test using erythromycin and clindamycin (17,27). Against the ermA-, ermB-, or ermC-carrying MSSA strains, clarithromycin and azithromycin were inactive regardless of the inducible or constitutive resistance phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Target site modifications and active efflux pumps are known to be the predominant macrolide resistance mechanisms in streptococci and staphylococci (17,27,28). As for the target site modification, some methylase enzymes encoded by the erm genes induce dimethylation of an adenine residue in domain V, the peptidyltransferase site, of a 23S ribosomal subunit, which results in reduced binding affinity to macrolide, lincosamide (clindamycin), and streptogramin B (MLS B ) antibiotics.…”

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confidence: 99%

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In Vitro Antibacterial Activity of Modithromycin, a Novel 6,11-Bridged Bicyclolide, against Respiratory Pathogens, Including Macrolide-Resistant Gram-Positive Cocci

Sato

Tateda

Kimura

et al. 2011

Antimicrob Agents Chemother

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The in vitro activities of modithromycin against Gram-positive and -negative respiratory pathogens, including macrolide-resistant cocci with different resistance mechanisms, were compared with those of other macrolide and ketolide agents. MICs were determined by the broth microdilution method. All 595 test strains used in this study were isolated from Japanese medical facilities. The erm (ribosome methylase) and/or mef (efflux pump) gene, which correlated with resistance to erythromycin as well as clarithromycin and azithromycin, was found in 81.8%, 21.3%, and 23.2% of Streptococcus pneumoniae, Streptococcus pyogenes, and methicillin-susceptible Staphylococcus aureus (MSSA) strains, respectively. Modithromycin showed MIC 90 s of 0.125 g/ml against these three cocci, including macrolide-resistant strains. In particular, the MIC of modithromycin against ermB-carrying S. pyogenes was >32-fold lower than that of telithromycin. The activities of modithromycin as well as telithromycin were little affected by the presence of mefA or mefE in both streptococci. Against Gram-negative pathogens, modithromycin showed MIC 90 s of 0.5, 8, and 0.031 g/ml against Moraxella catarrhalis, Haemophilus influenzae, and Legionella spp., respectively. The MICs of modithromycin against M. catarrhalis and H. influenzae were higher than those of telithromycin and azithromycin. However, modithromycin showed the most potent anti-Legionella activity among the macrolide and ketolide agents tested. These results suggested that the bicyclolide agent modithromycin is a novel class of macrolides with improved antibacterial activity against Gram-positive cocci, including telithromycin-resistant streptococci and intracellular Gram-negative bacteria of the Legionella species.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

In Vitro Antibacterial Activity of Modithromycin, a Novel 6,11-Bridged Bicyclolide, against Respiratory Pathogens, Including Macrolide-Resistant Gram-Positive Cocci

Sato

Tateda

Kimura

et al. 2011

Antimicrob Agents Chemother

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“…Regarding macrolide resistance determinants, little is known about them in mutans group streptococci other than S. mutans strain V1, which was isolated from the heart valve of an infected endocarditis patient and showed resistance to erythromycin by carrying a gene homologous to erm(B) of S. pneumoniae (Nemoto et al, 2008). The erm(B) gene was shown to confer resistance to lincosamides and 14-, 15-and 16-membered-ring macrolides (Syrogiannopoulos et al, 2003); it was carried by either Tn917 or omega elements and each element was integrated into the Tn916 transposon, which carries the tetracycline resistance gene tet(M) in S. pneumoniae (Croucher et al, 2011). Of note is that the Tn916-related transposons Tn6002, Tn6003 and Tn3872 containing an unexpressed 'silent' tet(M) were found in erm(B)-positive tetracycline-susceptible isolates of S. pneumoniae, S. mitis and S. oralis (Cochetti et al, 2007;Brenciani et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Identification of A2059G 23S rRNA and G439A rplC gene mutations in Streptococcus criceti strain OMZ 61, a strain resistant to azithromycin, josamycin and clindamycin

2015

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Streptococcus criceti is a cariogenic organism that belongs to the mutans streptococci. Of the four S. criceti strains, strain OMZ 61 has been identified as being resistant to erythromycin. Antimicrobial susceptibility testing showed that strain OMZ 61 is also resistant to azithromycin, josamycin and clindamycin but susceptible to tetracycline and tiamulin. DNA hybridization analysis of the 23S rRNA genes revealed that the hybridization patterns in strain OMZ 61 differed from those in the other three strains. We further analyzed the nucleotide sequences of a ribosomal RNA operon, the rrnD operon, and the rpsJ−rpsQ region including rplC and rplD genes for ribosomal proteins L3 and L4, respectively, in the four strains studied. Nucleotide sequence analysis indicated that strain OMZ 61 contains an A-to-G substitution at nucleotide position 2059, equivalent to Escherichia coli numbering 2058, in a 23S rRNA gene (rrlD) and a G-to-A substitution at nucleotide position 439 in the rplC gene, suggesting an amino acid residue change at position 147 from valine to isoleucine, whereas no mutation in the rplD gene was found. DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis showed that most or all of the 23S rRNA genes in strain OMZ 61 contain the A2059G mutation. These findings suggest that the resistance to erythromycin, azithromycin, josamycin and clindamycin in strain OMZ 61 is conferred by alterations in 23S rRNA and/or ribosomal protein L3. This is the first description of mutations in the 23S rRNA and rplC genes in mutans streptococci.

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“…Telithromycin retains excellent antimicrobial activity against Mef(E)/Mel-containing pneumococci (12,49). However, more detailed reports showed that the efflux pump conferred small increases in pneumococcal MICs of telithromycin after preincubation with subinhibitory concentrations of telithromycin (12,49) or in comparison to the MICs of clinical isolates with and without mef(E)-mel (46). To determine whether the lack of telithromycin resistance was due to an inefficient induction of mef(E)-mel expression or poor efflux of telithromycin by Mef(E)/Mel, the inducing ability of telithromycin was tested in the disk diffusion assay.…”

Section: Environmental or Antibiotic (Nonmacrolide) Stress And Competmentioning

confidence: 99%

Induction of Efflux-Mediated Macrolide Resistance in Streptococcus pneumoniae

Chancey

Zhou

Zähner

et al. 2011

Antimicrob Agents Chemother

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The antimicrobial efflux system encoded by the operon mef(E)-mel on the mobile genetic element MEGA in Streptococcus pneumoniae and other Gram-positive bacteria is inducible by macrolide antibiotics and antimicrobial peptides. Induction may affect the clinical response to the use of macrolides. We developed mef(E) reporter constructs and a disk diffusion induction and resistance assay to determine the kinetics and basis of mef(E)-mel induction. Induction occurred rapidly, with a >15-fold increase in transcription within 1 h of exposure to subinhibitory concentrations of erythromycin. A spectrum of environmental conditions, including competence and nonmacrolide antibiotics with distinct cellular targets, did not induce mef(E). Using 16 different structurally defined macrolides, induction was correlated with the amino sugar attached to C-5 of the macrolide lactone ring, not with the size (e.g., 14-, 15-or 16-member) of the ring or with the presence of the neutral sugar cladinose at C-3. Macrolides with a monosaccharide attached to C-5, known to block exit of the nascent peptide from the ribosome after the incorporation of up to eight amino acids, induced mef(E) expression. Macrolides with a C-5 disaccharide, which extends the macrolide into the ribosomal exit tunnel, disrupting peptidyl transferase activity, did not induce it. The induction of mef(E) did not require macrolide efflux, but the affinity of macrolides for the ribosome determined the availability for efflux and pneumococcal susceptibility. The induction of mef(E)-mel expression by inducing macrolides appears to be based on specific interactions of the macrolide C-5 saccharide with the ribosome that alleviate transcriptional attenuation of mef(E)-mel.Macrolides are broad-spectrum antibiotics with complex macrocyclic 14-, 15-, or 16-member lactone rings that bind in the peptide exit tunnel of bacterial ribosomes and inhibit protein synthesis. Macrolides are often recommended as the empirical first-line treatment for upper respiratory bacterial infections, including pneumococcal infections and communityacquired pneumonia. However, bacterial resistance to macrolides is expanding worldwide in Gram-positive bacteria and is now present in almost a third of all invasive Streptococcus pneumoniae isolates (14). The two most common mechanisms of macrolide resistance in bacterial pathogens are modification of the bacterial ribosome, either by methylation or mutation, and extrusion of the drugs from the bacterial cell by an efflux pump. Genes of the erm (erythromycin ribosomal methylases) family of rRNA methylases confer high-level resistance to lincosamides and streptogramins, as well as macrolides (the MLS B phenotype), and can be constitutive or inducible. In the inducible form, resistance develops only after exposure of the bacterium to the macrolide.The best-studied mechanism of inducible MLS B resistance involves the erm(C) gene found in S. aureus and other Grampositive pathogens (4,32,33). Translation of erm(C) is attenuated in the absence of inducers due to...

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Antimicrobial Susceptibility and Macrolide Resistance Inducibility of Streptococcus pneumoniae Carrying erm (A), erm (B), or mef (A)

Cited by 23 publications

References 15 publications

In Vitro Antibacterial Activity of Modithromycin, a Novel 6,11-Bridged Bicyclolide, against Respiratory Pathogens, Including Macrolide-Resistant Gram-Positive Cocci

In Vitro Antibacterial Activity of Modithromycin, a Novel 6,11-Bridged Bicyclolide, against Respiratory Pathogens, Including Macrolide-Resistant Gram-Positive Cocci

Identification of A2059G 23S rRNA and G439A <i>rplC</i> gene mutations in <i>Streptococcus criceti</i> strain OMZ 61, a strain resistant to azithromycin, josamycin and clindamycin

Induction of Efflux-Mediated Macrolide Resistance in Streptococcus pneumoniae

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