Clinical Isolates of Staphylococcus aureus with Ribosomal Mutations Conferring Resistance to Macrolides

Abstract

Six strains of Staphylococcus aureus isolated from cystic fibrosis patients after treatment with azithromycin were cross-resistant to azithromycin and erythromycin. None of the isolates contained erm or msr(A) genes, but they all carried either A2058G/U or A2059G mutations within the rrl genes, with a majority of the rRNA copies bearing the mutation. One strain displayed an additional mutation in the rplV gene, encoding the L22 ribosomal protein

Influence of Disk Separation Distance on Accuracy of the Disk Approximation Test for Detection of Inducible Clindamycin Resistance inStaphylococcusspp

“…This is similar to the rate described in other studies (6,19,30). Possible explanations include mutations in the primer binding site and the presence of rare resistance mechanisms (21,26,30,36).…”

In Vitro Selection and Characterization of Resistance to Macrolides and Related Antibiotics in Mycoplasma pneumoniae

“…In M. pneumoniae, resistance by mutation is the most expected mechanism of resistance, and so far it is the only one described in this species (20,22), since this mycoplasma harbors only one copy of the rRNA gene operon (18). Thus, heterozygous strains or gene dosage effect, previously described for Mycoplasma hominis (13,23) or other bacteria (19,25) with at least two copies of rRNA, could not exist in M. pneumoniae.…”

“…Three main mechanisms of resistance have been reported: drug inactivation, active efflux, and modification of the target sites by methylation or mutation (29,34). Mutations in domains II and V of 23S rRNA and in ribosomal proteins L4 and L22 were involved in resistance to MLSKs, first in bacteria with a small number of rrn operons and more recently in bacteria like Streptococcus pneumoniae and Staphylococcus aureus with four and six rrn operons, respectively (25,29,32). In mycoplasmas, gram-positive related bacteria which possess one or two copies of 23S rRNA, only resistance by point mutations in the peptidyltransferase loop of domain V of 23S rRNA has been described (13,20,22,23).…”

The strongest resistance of Staphylococcus aureus to erythromycin is caused by decreasing uptake of the antibiotic into the cells

“…Previous investigations revealed that rare macrolide resistance mechanisms in S. aureus are connected with a mutation in the 23S rRNA subunit and with enzymatic inactivation of the antibiotic by phosphotransferase coded by the mph(C) gene [8,13,21,22]. Research to identify those mechanisms was not carried out in our study but if those 13% of strains represented the type of resistance connected with enzymatic inactivation, it would be more frequent than has been thought so far [8]. Thus, we postulate that in those 13% of strains, a hitherto unknown mechanism is responsible for erythromycin resistance in S. aureus.…”

“…In a few strains, gene mutations connected with ribosomal proteins and rRNA have been found. The mutations decrease the susceptibility of these bacteria to this group of antibiotics [8]. A mechanism of resistance caused by a barrier to macrolide permeability has not yet been found in these bacteria, although it is suggested that such a mechanism may play a crucial role in S. aureus resistance to acriflavine [9].…”