Conjugative transfer frequencies of mef(A)-containing Tn1207.3 to macrolide-susceptible Streptococcus pyogenes belonging to different emm types

Hadjirin, Nazreen F.; Harrison, Ewan M.; Holmes, Mark A.; Paterson, Gavin K.

doi:10.1111/lam.12213

Cited by 5 publications

(1 citation statement)

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“…Conjugal transfer rates of Tn1703.1 carrying mef(A) have been found to be highly variable between different S. pyogenes emm-types, ranging in frequencies of 1.13 Â 10 26 to 7.2 Â 10 28 in various isolates, with higher frequencies in emm1 and emm4 isolates (Hadjirin et al 2013). The mef(A) gene has also been found on a large chimeric chromosomal element that also carries the tet(O) gene, an element that lends a distinct SmaI-typable pulse-field gel electrophoresis profile to isolates carrying the construct (Brenciani et al 2004;Bacciaglia et al 2007).…”

Section: Acquired Macrolide Efflux Mechanismsmentioning

confidence: 99%

Resistance to Macrolide Antibiotics in Public Health Pathogens

Fyfe

Grossman

Kerstein

et al. 2016

Cold Spring Harb Perspect Med

163

140

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Macrolide resistance mechanisms can be target-based with a change in a 23S ribosomal RNA (rRNA) residue or a mutation in ribosomal protein L4 or L22 affecting the ribosome's interaction with the antibiotic. Alternatively, mono-or dimethylation of A2058 in domain V of the 23S rRNA by an acquired rRNA methyltransferase, the product of an erm (erythromycin ribosome methylation) gene, can interfere with antibiotic binding. Acquired genes encoding efflux pumps, most predominantly mef(A) þ msr(D) in pneumococci/streptococci and msr(A/B) in staphylococci, also mediate resistance. Drug-inactivating mechanisms include phosphorylation of the 2 0 -hydroxyl of the amino sugar found at position C5 by phosphotransferases and hydrolysis of the macrocyclic lactone by esterases. These acquired genes are regulated by either translation or transcription attenuation, largely because cells are less fit when these genes, especially the rRNA methyltransferases, are highly induced or constitutively expressed. The induction of gene expression is cleverly tied to the mechanism of action of macrolides, relying on antibiotic-bound ribosomes stalled at specific sequences of nascent polypeptides to promote transcription or translation of downstream sequences. Macrolide antibiotics are polyketides composed of a 14-, 15-, or 16-membered macrocyclic lactone ring (14-, 15-, and 16-membered) to which several sugars and/or side chains have been attached by the producing organism or as modifications during semisynthesis in the laboratory (Figs. 1 and 2). Newer semisynthetic derivations, like ketolides telithromycin, and solithromycin, have a C3-keto group in place of the C3 cladinose (akin to naturally occurring pikromycin) (Brockmann and Henkel 1950) and an 11,12-cyclic carbamate with an extended alkyl -aryl side chain that increases the affinity of the antibiotic for the ribosome by 10-to 100-fold (Hansen et al. 1999;Dunkle et al. 2010); in the case of solithromycin, a fluorine substituent at C2 provides an additional ribosomal interaction (Llano-Sotelo et al. 2010). Macrolides continue to be important in the therapeutic treatment of community-acquired pneumonia (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and atypicals Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae), sexually transmitted diseases (Neiserria gonorhoeae, Chlamydia trachomatis, Mycoplasma genitalium), shigellosis, and salmonellosis. With solithromycin heading for a new drug application (NDA) filing in 2016 and having the in vitro potency to treat erythromycin-resistant

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Section: Acquired Macrolide Efflux Mechanismsmentioning

confidence: 99%