Naslov
RIBOSOMAL ANTIBIOTICS - BACTERIAL RESISTANCE PROBLEM AND POSSIBLE SOLUTIONS

Autori
Maravić, Gordana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Acta Microbiologica et Immunologica Hungarica / Marialigeti, K ; Sipos, R. - Budimpešta : Akadémiai Kiadó, 2005

Skup
Central European Forum for Microbiology

Mjesto i datum
Keszthely, Mađarska, 26.10.2005. - 28.10.2005

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
ribosome; antibiotics; antibiotic resistance; RNA methylation; inhibitor

Sažetak
The bacterial ribosome is a target for several classes of anitibiotics that are currently in clinical use. Among them, two classes are most extensively utilised: possibly the safest macrolide-lincosamide-streptogramin B (MLS) antibiotics and the most potent known aminoglycoside antibiotics. As the worldwide problem of antibiotic resistance is constantly reducing effectiveness of existent drugs, the studies of resistance mechanisms continue to be of the utmost importance. There are more than a few mechanisms of resistance found for the MLS and aminoglycoside antibiotics. Many of them use strong pumps to expel drugs out of a cell or enzymes that modify either antibiotic itself or the antibiotic binding site, i.e. RNA. Intrestingly, a vast number of clinical strains employ a common mechanism of RNA methylation to protect the protein synthesis machinery from the destructive action of antibiotics. This is a particularly powerful system horizontally transferred from many antibiotic producing bacteria. In contrast to other target site modifications, like RNA mutations that are found only in a portion of the rRNA genes, the methylation of antibiotic target is an extremely efficient mechanism, since it modifies all rRNA copies and generates high level of resistance. The most prevalent mechanism of the MLS resistance is exhibited by the action of the enzymes from the erythromycin ribosome methylase (Erm) family. Erm enzymes methylate specific adenine residue within 23S rRNA, thus preventing antibiotic binding to the ribosome. On the other hand, the self-defense mechanism of natural producers of deoxystreptamine-containing aminoglycoside antibiotics is methylation of a specific guanine residue within the 16S rRNA. In addition, this is a relatively new mechanism of resistance found in members of clinically important Enterobacteriaceae family and in Pseudomonas aeruginosa and Serratia marcescens clinical strains. Methylation of 16S rRNA in aminoglycoside resistant bacteria is carried out by enzymes from the aminoglycoside resistance methylase (Arm) family. The results of recent biochemical studies of members of both Erm and Arm family will be presented and discussed in light of possible application in design of specific methyltransferase inhibitors. Potential solution will be put in perspective to propose new directions to overcome the threatening problem of MLS and aminoglycoside resistance.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA