engleski

Molecular evolution of antibiotic resistance determinants

The widespread and often inappropriate use of antibiotics has drastically influenced the emergence and spread of antibiotic resistant bacterial strains. Many pathogens have become resistant to several different classes of antimicrobials, thus making the antibiotic resistance one of the top priorities of public health. A substantial number of potent and widely used antibiotics inhibit the bacterial cell growth by interfering with the essential cellular process of translation. We now know that the ribosomal RNA is responsible both for the enzymatic properties of the ribosome and for most of the contacts with the antibiotics. It is therefore to expect that changes that confer antibiotic resistance are mainly found in the rRNA. In contrast to RNA mutations that are found only in a portion of the rRNA genes, the methylation of a specific nucleotide within the rRNA is most common mechanism of resistance to ribosome-targeting drugs in pathogenic bacteria with multiple rRNA operons. Methyltransferases (MTases) responsible for these modifications modify all rRNA copies and thus generate high level of resistance. The 30S subunit is a target for aminoglycoside antibiotics. Many different resistance mechanisms to these antibiotics have been described in clinical strains, but until recently the methylation of rRNA was not among them. In the last few years, however, new types of highly aminoglycoside resistant pathogens have emerged that carry Arm and Kam MTases, specific for G1405 and A1408, respectively, which were previously restricted exclusively to antibiotic producers. Several genes have recently been isolated from plasmids that are now rapidly spreading by horizontal transfer, thus representing a threat to successful treatment of bacterial infections. Our recent studies on the mechanisms of resistance to aminoglycoside antibiotics based on the action of aminoglycoside resistance MTases will be presented and discussed. Our latest results will be put in the evolutionary perspective with the special emphasis on the origin and mechanism of this type of resistance and selective pressure that led to its rapid dissemination.

antibiotic resistance; mechanisms; evolution

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