Background/PurposeMutations in rpsL and rrs genes are associated with resistance to streptomycin in tuberculosis, but important geographical variation exists in these mutations. Key words: Mycobacterium tuberculosis, Streptomycin, drug resistance, rpsL gene, rrs gene. Streptomycin, the first antibiotic used in tuberculosis control programs, perturbs protein synthesis at the ribosome level. Genome Med. Three different types of missense mutations were identified in ten high‐level kanr mutants at codons 129, 262 and 263 (Table 2). In addition to rpsL, the rrs gene (which encodes 16S ribosomal RNA) has been implicated in streptomycin resistance with a frequency of about 10%. rpsL carried by plasmids efficiently sensitizes streptomycin-resistant mutants. Currently, mutations in three genes, namely rrs, rpsL, and gidB, encoding 16S rRNA, ribosomal protein S12, and 16S rRNA-specific methyltransferase, respectively, are considered to be involved in conferring resistance to streptomycin (STR) in Mycobacterium tuberculosis. Among the 25 strains displaying isolated resistance to streptomycin, 18 were identified by DNA sequencing to have mutations responsible for STR resistance in the rpsL gene (K43R and K88R) or in the rrs gene (A513C, C516T, and A907C). 6 Mutations associated with streptomycin resistance in Mycobacterium tuberculosis have been identified in the rpsL and rrs genes, which encode the ribosomal protein S12 and 16S rRNA, respectively. Genetic analyses revealed that a streptomycin-resistant mutation str-6 in strain TK24 is responsible for induction of antibiotic synthesis. Streptomycin-resistant mutants Sm6 and Sm13, transformed with a plasmid carrying wt rpsL, pRpsL-wt (A), or rpsL having multiple silent mutations, pRpsL-sil (B), become more sensitive to streptomycin than mutants transformed with a plasmid carrying a mock gene, pRpsLΔ4. Abstract Streptomycin (SM) is one of the most effective drugs for the treatment of multidrug resistant (MDR) TB. Streptomycin resistance in both gram-positive and gram-negative bacteria is usually caused by a single mutation in the rpsL gene. The recent emergence of indolent and rapidly fatal drug-resistant strains of Mycobacterium tuberculosis has renewed interest in defining the molecular mechanisms of drug resistance in the tubercle bacilli. Finken M, Kirschner P, Meier A, Wrede A, Böttger EC. 1994 Feb;38(2):238-42. doi: 10.1128/aac.38.2.238. Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India. 1996 ). Recall that certain mutations in the rpsl gene of Bacteria can lead to streptomycin-resistance. Streptomycin resistance frequently results from a mutation in the open reading frame of rpsL (Ochi et al. Munir A, Kumar N, Ramalingam SB, Tamilzhalagan S, Shanmugam SK, Palaniappan AN, Nair D, Priyadarshini P, Natarajan M, Tripathy S, Ranganathan UD, Peacock SJ, Parkhill J, Blundell TL, Malhotra S. Sci Rep. 2019 Jul 16;9(1):10283. doi: 10.1038/s41598-019-46756-x. The strB gene, encoding an aminoglycoside 6‐phosphotransferase that inactivates streptomycin, was detected in all Chilean strains, including sensitive and resistant strains. 1996 ). In conclusion, the streptomycin resistance caused by rpsL the highest frequency in streptomycin-resistant clinical isolates of mutations usually made the bacteria less competitive than its wild- Mycobacterium tuberculosis, while the K87R mutant was also type strain in the absence of … Other molecular mechanisms, such as reduced cell permeability to aminoglycosides or presence of drug-modifying enzymes, might contribute to its streptomycin resistance. Copyright © 2012 Published by Elsevier Taiwan LLC. Mutations related to streptomycin resistance in the rpsL and rrs genes are well known and can explain about 70% of this phenotypic resistance. Streptomycin-resistant mutants Sm6 and Sm13, transformed with a plasmid carrying wt rpsL, pRpsL-wt (A), or rpsL having multiple silent mutations, pRpsL-sil (B), become more sensitive to streptomycin than mutants transformed with a plasmid carrying a mock gene, pRpsLΔ4. rapid detection of drug resistance against isoniazid, rifampicin, amikacin, capreomycin, streptomycin and fluoroquinolones in Mycobacterium tuberculosis. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Mutations at this same site confer SmR in Escherichia coli. Tuber Lung Dis. [Google Scholar] Ohama T, Yamao F, Muto A, Osawa S. Organization and codon usage of the streptomycin operon in Micrococcus luteus, a bacterium with a high genomic G + C content. Susceptibility tests were carried out using the fluorometric method, and rrs and rpsL DNA sequencing was performed by capillary electrophoresis. However, resistance to SM is increasingly reported mainly due to mutations in rpsL … 2019 Oct 22;35(11):165. doi: 10.1007/s11274-019-2749-z. Read 1 answer by scientists to the question asked by Merijn L M Salverda on Feb 13, 2020 The presence of the aadE gene encoding aminoglycoside 6-adenylyltransferase was also evaluated. The rpsL gene and streptomycin resistance in single and multiple drug-resistant strains of Mycobacterium tuberculosis. It is shown here that streptomycin resistance in some clinical isolates of Mycobacterium tuberculosis is associated either with missense mutations in the rpsL … 1995 Apr;171(4):954-60. doi: 10.1093/infdis/171.4.954. Incidence of resistance is increasingly reported. We amplified, sequenced and compared the rpsL gene of the wild‐type and kan r strains. Erwinia amylovora can rapidly become highly resistant to applications of the antibiotic streptomycin through a single nucleotide mutation in the rpsL gene, which causes an amino acid substitution that prevents inhibitory binding of streptomycin … We use cookies to help provide and enhance our service and tailor content and ads. Mutation K43R in rpsL was strongly associated with high-level streptomycin resistance (P < 0.01), while mutations in rrs and gidB potentially contributed to low-level resistance (P < 0.05). The rrs gene encodes 16S rRNA and its most frequent mutations are in loop 530 and region 912. rpsL carried by plasmids efficiently sensitizes streptomycin-resistant mutants. The rpsL gene and streptomycin resistance in single and multiple drug‐resistant strains of Mycobacterium tuberculosis Jaygopal Nair Laboratory of Mycobacteria, Center for Biologics Evaluation and Research, United States Food and Drug Administration, 8800 … Mycobacteria were isolated from patients with suspected drug-resistant tuberculosis. The rpsL gene encodes the S12 protein of the ribosomal complex. The hot mutation sites in H. parasuis also indicates that the K → R mutations in 43rd and 88th codons in rpsL, which encodes the highly conserved RpsL protein of the ribosomal accuracy centre (Toivonen, Boocock & Jacobs, 1999), have a greater propensity to confer drug resistance to streptomycin than rrs and other mutation sites. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. To characterize the mechanisms of streptomycin (STR) resistance in Campylobacter coli, we chose 17 isolates that were resistant to STR, erythromycin (ERY), or both, and the putative STR resistance target genes rpsL, rrs, and gidB were analyzed for mutations. 2018 Oct 17;9(1):4306. doi: 10.1038/s41467-018-06634-y. Mutations therefore genetically alter the number of rpsL and rrs alleles contained in the bacterial genome. 1993 Nov; 10 (3):521–527. The complete recessiveness of rpsL streptomycin resistance mutations explains the absence of resistant mutants in the multicopy treatment because even if the plasmid-mediated copy of rpsL mutates and reaches fixation prior to plating, the wild-type chromosomal copy of the gene masks the resistance phenotype. The objectives of this study were to characterise mutations in rrs, rpsL and gidB genes in Mycobacterium tuberculosis isolates from Thailand and to examine possible associations between mutations and strain genotypes. 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