ژن های مقاوم چندگانه cfr و مشابه cfr The cfr and cfr-like multiple resistance genes

1. Introduction There is an increasing concern about pathogenic bacteria obtaining resistance to the antibiotics used for treatment of humans and animals. To address the problems with antibiotic resistance we need knowledge about the various resistance mechanisms, how they can be disseminated, which bacteria contain them and where they come from. Antibiotic resistance is not a new phenomenon, see e.g. review by [1]. There are many ways bacteria can obtain and exert antibiotic resistance and new resistance determinants are continuously discovered. The strategies bacteria use to evade the effects of antibiotics, can be grouped into three general mechanisms: increased antibiotic efflux out of the cell or reduced antibiotic influx into the cell, enzymatic inactivation of antibiotics through drug modification or cleavage, and the alteration of the antibiotic binding site. A bacterial cell contains many different target sites for antibiotics, but in general, an antibiotic interfere with or inhibits an essential cellular pathway or process. The most common antibiotic targets include bacterial cell wall synthesis; the bacterial membrane; the DNA replication machinery; RNA polymerase; the folate biosynthesis pathway; and the protein synthesis machinery. The ribosome is a major site of antibiotic action in the bacterial cell and is targeted by a large and chemically diverse group of antibiotics. A number of these antibiotics have important applications in human and veterinary medicine in the treatment of bacterial infections. The antibiotic binding sites are clustered at functional centers of the ribosome, such as the decoding center on the 30S subunit, the peptidyl transferase center (PTC), the GTPase center, and the peptide exit tunnel on the 50S subunit and the subunit interface in the 70S ribosome. The resistance mechanisms to antibiotics targeting the ribosomes include all three mechanism mentioned above. The alterations of the ribosomal antibiotic binding sites providing antibiotic resistance can be either mutation or methylation. While mutations appear spontaneously the gaining of methylations normally need a gene transfer of a methyl transferase gene. Since the 1950s, about 17 methyltransferases providing antibiotic resistance has been discovered, reviewed by [2,3]. One of the most recently discovered and most exceptional regarding nature of modification and mechanism of methylation is the Cfr methyltransferase [4e7] and Cfr and Cfr-like proteins have a potential to become a serious threat for antibiotic treatment. The sections below will present an overview of our current knowledge about Cfr and Cfr-like methyltransferases and especially cover aspects that have not previously been reviewed.