2009 3 4 1 Journal of Microbes and Infection, March 2009, Vol. 4, No. 1 45 : 16S rrna,, 200025 : 30S 16S rrna A 16S rrna, 4, 6- - ( ), G + C G + C, 16S rrna,, : 16S rrna ; ; A novel aminoglycoside resistance determinant: plasmid-mediated 16S rrna methylase WU Qiong, NI Yu-Xing Department of Clinical Microbiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Abstract: Aminoglycosides have been used for the treatment of a broad range of life-threatening Gram-positive and Gram-negative bacterial infections. These agents bind to the A site of the 16S rrna of the bacterial 30S ribosomal subunit and subsequently block growth through interference with protein synthesis. The mechanisms of resistance to aminoglycosides in pathogenic bacteria were previously believed to be restricted to production of aminoglycosidemodifying enzymes, a decrease in intracellular antibiotic accumulation, and the substitution of ribosomal proteins or mutation of rrna. Plasmid-mediated 16S rrna methylases, which confer a high level of resistance to various clinically important aminoglycosides, including 4, 6-disubstituted deoxystreptamine aminoglycoside, were reported to be involved as part of a novel aminoglycoside resistance mechanism in pathogenic Gram-negative rods. At present, six types of plasmid-mediated 16S rrna methyltransferase genes, arma, rmta, rmtb, rmtc, rmtd, and npma have been found in members of the family Gram-negative bacilli. Also, these genes are mediated by bacterium-specific recombination systems, such as transposons, and are easily translocated to other DNA target sites. The 16S rrna methylases were supposed to have originated from a self-defense mechanism in aminoglycoside-producing actinomycetes, however, the different G + C content of the methylase genes between Gram-negative bacilli and actinomycetes challenged this theory. The true origination of these six types of methylases requires further study. The selection pressure exerted by a variety of antibiotics will therefore promote the dissemination of genetic elements encoding the methylases. Because of the clinical importance of these enzymes, the further global dissemination of 16S rrna methylase genes among pathogenic bacilli will be a cause of great concern in the near future. This review is about the mechanism of resistance, classification, genetic environment, and epidemiology of 16S rrna methylase. Key words: 16S rrna methylase; Plasmid; Aminoglycoside : :, E-mail: yuxing_ni@ yahoo. com. cn Corresponding author: NI Yu-Xin, E-mail: yuxing_ni@ yahoo. com. cn,, 30S 16S rrna
46 2009 3 4 1 Journal of Microbes and Infection, March 2009, Vol. 4, No. 1 A,,,, 16S rrna, 1 16S rrna 4 [ 1] : ;, ( aminoglycoside acetyltransferase, AAC) ( aminoglycoside nucleotidyltransferase, ANT AAD) ( aminoglycoside phosphotransferase, APH) ; 16S rrna ;, ( arbekacin),, 6 2", [ 2] 6 -N- -2 -O-, S-,, 16S rrna 16S rrna,, [ 3 ] [ 4-6] 16S rrna 4, 6- - ( 4, 6- disubstituted deoxystreptamine aminoglycoside),,, 16S rrna 2 16S rrna 6 16S rrna, arma rmta rmtb rmtc rmtd npma 2. 1 arma arma BM4536 [ 3 ] /,, 5-episisomicin, 2-6 -N-ethylnetilmicin, - ant3 9, aac3- arma arma Tn1548, IncL/ M [ 7], IncN [ 4] arma bla CTX-M [ 8], ArmA CTX-M [ 9 ], Liou [ 10], arma ArmA 16S rrna N7-G1405, 4, 6-3, G1405 G1405,, ArmA, Agr ( aminoglycoside resistance) ( GrmA GrmB FmrO Sgm Kgm Kmr NbrB KgmB MagrA) arma G + C 30%, G + C > 60%, arma arma 2. 2 rmta,, 16S rrna, rma [ 1 1], Tn5041 rma [ 12], AR-2, rma ( 1)
2009 3 4 1 Journal of Microbes and Infection, March 2009, Vol. 4, No. 1 47 trna orfa; rma Na + / H + ( 2) rmta 6. 2 kb, 262 bp orfq rmta AR-11, rmta 2, orfa 5, IS6100 rmta orfq-orfi rmta G + C 55%, 16S rrna G + C 64% 72%, rmta 2. 3 rmtb rmtb [ 13 ] S-95 ( MIC > 1 024 mg/ L),, RmtA 82%, 16S rrna, rmtb, Tn3 RmtB RmtA, 4, 6- -, RmtB 16S rrna, 33% 2. 4 rmtc rmtc [ 14], 16S rrna, G + C 41. 1% RmtC 16S rrna ( ArmA RmtA RmtB ),, ( 29% ), 16S rrna ( 28% ) rmtc ISEcp1 [ 14, 15 ], tnpa, rmtc 2. 5 rmtd rmtd, SPM-1 [ 16] rmtd G + C 59%, RmtB 42%, RmtA 40% RmtD, rmtd 2. 6 npma npma, ARS3 [ 17 ] NpmA 16S rrna KamA, 30% 4, 6- -, 4, 5- -, NpmA N-1, 16S rrna A A1408 3 16S rrna RNA, 16S rrna 9, 6 ( 1), 9 RNA A m 5 C1407, 2 16S rrna 1 KamA, istamycin Streptomyces tenjimariensis, A1408 N-1 2 GmrA, G1405 N-7 7-, ( Micromonospora 1 16S rrna Fig 1. Dendrogram of 16S rrna methylases
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