Association of streptomycin resistance mutations with level of drug resistance and Mycobacterium tuberculosis genotypes

OBJECTIVES: To determine 1) the relationship between specific streptomycin (SM) resistance mutations and the minimum inhibitory concentration (MIC), and 2) whether these mutations are preferentially associated with the Beijing genotype in Viet Nam.METHODS: A total of 131 consecutive Mycobacterium tu...

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Veröffentlicht in:The international journal of tuberculosis and lung disease 2012-04, Vol.16 (4), p.527-531
Hauptverfasser: Nhu, N. T. Q., Lan, N. T. N., Phuong, N. T. N., van V. Chau, N., Farrar, J., Caws, M.
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container_end_page 531
container_issue 4
container_start_page 527
container_title The international journal of tuberculosis and lung disease
container_volume 16
creator Nhu, N. T. Q.
Lan, N. T. N.
Phuong, N. T. N.
van V. Chau, N.
Farrar, J.
Caws, M.
description OBJECTIVES: To determine 1) the relationship between specific streptomycin (SM) resistance mutations and the minimum inhibitory concentration (MIC), and 2) whether these mutations are preferentially associated with the Beijing genotype in Viet Nam.METHODS: A total of 131 consecutive Mycobacterium tuberculosis isolates resistant to either isoniazid (INH) or rifampicin (RMP), collected previously, were tested for SM resistance, spoligotyped and sequenced in the rpsL, rrs and gidB genes. The MIC for 50 mutants was also determined.RESULTS: Overall, 116/131 isolates were SM-resistant. The three most frequently occurring mutation sites in rpsL and rrs were at codon 43 of rpsL (72/116, 62.1%), rpsL88 (22/116, 18.9%) and rrs514 (8/116, 6.9%). Mutations in the rrs910 region were found in two isolates (1.7%), and three isolates had mutations in both rpsL and rrs (2.6%). gidB mutations were found in both resistant and susceptible strains. Among SM-resistant isolates resistant to INH/RMP, the Beijing genotype was strongly associated with rpsL43 mutation (aOR 23.6, 95%CI 2.9-193.4, P = 0.002). The median MIC for each mutation was as follows: rpsL43 = 256 μg/ml, rpsL88 = 16 μg/ml, 515 loop = 4 μg/ml, 910 region = 8 μg/ml, and double mutation = 256 μg/ml. We found a strong association between rpsL43 and high drug resistance levels, with all rpsL43 mutants having an MIC >256 μg/ml (P < 0.001).
doi_str_mv 10.5588/ijtld.11.0202
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T. Q. ; Lan, N. T. N. ; Phuong, N. T. N. ; van V. Chau, N. ; Farrar, J. ; Caws, M.</creator><creatorcontrib>Nhu, N. T. Q. ; Lan, N. T. N. ; Phuong, N. T. N. ; van V. Chau, N. ; Farrar, J. ; Caws, M.</creatorcontrib><description>OBJECTIVES: To determine 1) the relationship between specific streptomycin (SM) resistance mutations and the minimum inhibitory concentration (MIC), and 2) whether these mutations are preferentially associated with the Beijing genotype in Viet Nam.METHODS: A total of 131 consecutive Mycobacterium tuberculosis isolates resistant to either isoniazid (INH) or rifampicin (RMP), collected previously, were tested for SM resistance, spoligotyped and sequenced in the rpsL, rrs and gidB genes. The MIC for 50 mutants was also determined.RESULTS: Overall, 116/131 isolates were SM-resistant. The three most frequently occurring mutation sites in rpsL and rrs were at codon 43 of rpsL (72/116, 62.1%), rpsL88 (22/116, 18.9%) and rrs514 (8/116, 6.9%). Mutations in the rrs910 region were found in two isolates (1.7%), and three isolates had mutations in both rpsL and rrs (2.6%). gidB mutations were found in both resistant and susceptible strains. Among SM-resistant isolates resistant to INH/RMP, the Beijing genotype was strongly associated with rpsL43 mutation (aOR 23.6, 95%CI 2.9-193.4, P = 0.002). The median MIC for each mutation was as follows: rpsL43 = 256 μg/ml, rpsL88 = 16 μg/ml, 515 loop = 4 μg/ml, 910 region = 8 μg/ml, and double mutation = 256 μg/ml. We found a strong association between rpsL43 and high drug resistance levels, with all rpsL43 mutants having an MIC &gt;256 μg/ml (P &lt; 0.001).</description><identifier>ISSN: 1027-3719</identifier><identifier>EISSN: 1815-7920</identifier><identifier>DOI: 10.5588/ijtld.11.0202</identifier><identifier>PMID: 22640514</identifier><language>eng</language><publisher>Paris, France: International Union Against Tuberculosis and Lung Disease</publisher><subject>Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antitubercular Agents - pharmacology ; Bacterial diseases ; Bacterial Typing Techniques - methods ; Beijing Genotype ; Biological and medical sciences ; Drug Resistance ; Drug Resistance, Bacterial - genetics ; Genotype ; Human bacterial diseases ; Humans ; Infectious diseases ; Medical sciences ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - drug effects ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - isolation &amp; purification ; Pharmacology. Drug treatments ; Pneumology ; Respiratory system : syndromes and miscellaneous diseases ; RNA, Bacterial ; Sequence Analysis, RNA - methods ; Streptomycin ; Streptomycin - pharmacology ; Tuberculosis ; Tuberculosis and atypical mycobacterial infections ; Tuberculosis, Multidrug-Resistant - diagnosis ; Tuberculosis, Multidrug-Resistant - drug therapy ; Tuberculosis, Multidrug-Resistant - microbiology ; Vietnam</subject><ispartof>The international journal of tuberculosis and lung disease, 2012-04, Vol.16 (4), p.527-531</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-f4418815c17637bdc23e0cf0e23cfdb4553a57ce33cd2f043d201717bbad5c803</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25721568$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22640514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nhu, N. T. Q.</creatorcontrib><creatorcontrib>Lan, N. T. N.</creatorcontrib><creatorcontrib>Phuong, N. T. N.</creatorcontrib><creatorcontrib>van V. Chau, N.</creatorcontrib><creatorcontrib>Farrar, J.</creatorcontrib><creatorcontrib>Caws, M.</creatorcontrib><title>Association of streptomycin resistance mutations with level of drug resistance and Mycobacterium tuberculosis genotypes</title><title>The international journal of tuberculosis and lung disease</title><addtitle>Int J Tuberc Lung Dis</addtitle><description>OBJECTIVES: To determine 1) the relationship between specific streptomycin (SM) resistance mutations and the minimum inhibitory concentration (MIC), and 2) whether these mutations are preferentially associated with the Beijing genotype in Viet Nam.METHODS: A total of 131 consecutive Mycobacterium tuberculosis isolates resistant to either isoniazid (INH) or rifampicin (RMP), collected previously, were tested for SM resistance, spoligotyped and sequenced in the rpsL, rrs and gidB genes. The MIC for 50 mutants was also determined.RESULTS: Overall, 116/131 isolates were SM-resistant. The three most frequently occurring mutation sites in rpsL and rrs were at codon 43 of rpsL (72/116, 62.1%), rpsL88 (22/116, 18.9%) and rrs514 (8/116, 6.9%). Mutations in the rrs910 region were found in two isolates (1.7%), and three isolates had mutations in both rpsL and rrs (2.6%). gidB mutations were found in both resistant and susceptible strains. Among SM-resistant isolates resistant to INH/RMP, the Beijing genotype was strongly associated with rpsL43 mutation (aOR 23.6, 95%CI 2.9-193.4, P = 0.002). The median MIC for each mutation was as follows: rpsL43 = 256 μg/ml, rpsL88 = 16 μg/ml, 515 loop = 4 μg/ml, 910 region = 8 μg/ml, and double mutation = 256 μg/ml. We found a strong association between rpsL43 and high drug resistance levels, with all rpsL43 mutants having an MIC &gt;256 μg/ml (P &lt; 0.001).</description><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antitubercular Agents - pharmacology</subject><subject>Bacterial diseases</subject><subject>Bacterial Typing Techniques - methods</subject><subject>Beijing Genotype</subject><subject>Biological and medical sciences</subject><subject>Drug Resistance</subject><subject>Drug Resistance, Bacterial - genetics</subject><subject>Genotype</subject><subject>Human bacterial diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - drug effects</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - isolation &amp; purification</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology</subject><subject>Respiratory system : syndromes and miscellaneous diseases</subject><subject>RNA, Bacterial</subject><subject>Sequence Analysis, RNA - methods</subject><subject>Streptomycin</subject><subject>Streptomycin - pharmacology</subject><subject>Tuberculosis</subject><subject>Tuberculosis and atypical mycobacterial infections</subject><subject>Tuberculosis, Multidrug-Resistant - diagnosis</subject><subject>Tuberculosis, Multidrug-Resistant - drug therapy</subject><subject>Tuberculosis, Multidrug-Resistant - microbiology</subject><subject>Vietnam</subject><issn>1027-3719</issn><issn>1815-7920</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0c2L1DAYBvAiiruuHr1KL4KXjnnz0bTHZddVYUUEPYc0SccMbTLmY5fZv950On5cBHtIQ_jxhLxPVb0EtGGs697aXZr0BmCDMMKPqnPogDW8x-hx2SPMG8KhP6uexbhDCAMAf1qdYdxSxICeV_eXMXplZbLe1X6sYwpmn_x8UNbVwUQbk3TK1HNORxPre5u-15O5M9Pidcjbv510uv50UH6QKplg81ynPJig8uSLqbfG-XTYm_i8ejLKKZoXp_9F9e3m3derD83t5_cfry5vG0V7SM1IKXTlRQp4S_igFSYGqREZTNSoB8oYkYwrQ4jSeESUaIyAAx8GqZnqELmo3qy5--B_ZBOTmG1UZpqkMz5HAYXzFijQ_6GAy9Ivqc1KVfAxBjOKfbCzDIeCxFKLONYiAMRSS_GvTtF5mI3-rX_1UMDrE5BRyWkMZZg2_nGMY2BtV9yX1VlXRpmk2PkcXBmgsErYLI-XltaX0sUdtI6Kcj-gDjMBlFGhzSjzlESSQWwfRIS-ZF7_K3MNXN9SBosFOn7QnjaIChnSctKTn_jOydw</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Nhu, N. T. Q.</creator><creator>Lan, N. T. N.</creator><creator>Phuong, N. T. N.</creator><creator>van V. Chau, N.</creator><creator>Farrar, J.</creator><creator>Caws, M.</creator><general>International Union Against Tuberculosis and Lung Disease</general><general>International Union against Tuberculosis and Lung Disease</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20120401</creationdate><title>Association of streptomycin resistance mutations with level of drug resistance and Mycobacterium tuberculosis genotypes</title><author>Nhu, N. T. Q. ; Lan, N. T. N. ; Phuong, N. T. N. ; van V. Chau, N. ; Farrar, J. ; Caws, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-f4418815c17637bdc23e0cf0e23cfdb4553a57ce33cd2f043d201717bbad5c803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Antibacterial agents</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antitubercular Agents - pharmacology</topic><topic>Bacterial diseases</topic><topic>Bacterial Typing Techniques - methods</topic><topic>Beijing Genotype</topic><topic>Biological and medical sciences</topic><topic>Drug Resistance</topic><topic>Drug Resistance, Bacterial - genetics</topic><topic>Genotype</topic><topic>Human bacterial diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - drug effects</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - isolation &amp; purification</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology</topic><topic>Respiratory system : syndromes and miscellaneous diseases</topic><topic>RNA, Bacterial</topic><topic>Sequence Analysis, RNA - methods</topic><topic>Streptomycin</topic><topic>Streptomycin - pharmacology</topic><topic>Tuberculosis</topic><topic>Tuberculosis and atypical mycobacterial infections</topic><topic>Tuberculosis, Multidrug-Resistant - diagnosis</topic><topic>Tuberculosis, Multidrug-Resistant - drug therapy</topic><topic>Tuberculosis, Multidrug-Resistant - microbiology</topic><topic>Vietnam</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nhu, N. T. Q.</creatorcontrib><creatorcontrib>Lan, N. T. N.</creatorcontrib><creatorcontrib>Phuong, N. T. N.</creatorcontrib><creatorcontrib>van V. Chau, N.</creatorcontrib><creatorcontrib>Farrar, J.</creatorcontrib><creatorcontrib>Caws, M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>The international journal of tuberculosis and lung disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nhu, N. T. Q.</au><au>Lan, N. T. N.</au><au>Phuong, N. T. N.</au><au>van V. Chau, N.</au><au>Farrar, J.</au><au>Caws, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of streptomycin resistance mutations with level of drug resistance and Mycobacterium tuberculosis genotypes</atitle><jtitle>The international journal of tuberculosis and lung disease</jtitle><addtitle>Int J Tuberc Lung Dis</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>16</volume><issue>4</issue><spage>527</spage><epage>531</epage><pages>527-531</pages><issn>1027-3719</issn><eissn>1815-7920</eissn><abstract>OBJECTIVES: To determine 1) the relationship between specific streptomycin (SM) resistance mutations and the minimum inhibitory concentration (MIC), and 2) whether these mutations are preferentially associated with the Beijing genotype in Viet Nam.METHODS: A total of 131 consecutive Mycobacterium tuberculosis isolates resistant to either isoniazid (INH) or rifampicin (RMP), collected previously, were tested for SM resistance, spoligotyped and sequenced in the rpsL, rrs and gidB genes. The MIC for 50 mutants was also determined.RESULTS: Overall, 116/131 isolates were SM-resistant. The three most frequently occurring mutation sites in rpsL and rrs were at codon 43 of rpsL (72/116, 62.1%), rpsL88 (22/116, 18.9%) and rrs514 (8/116, 6.9%). Mutations in the rrs910 region were found in two isolates (1.7%), and three isolates had mutations in both rpsL and rrs (2.6%). gidB mutations were found in both resistant and susceptible strains. Among SM-resistant isolates resistant to INH/RMP, the Beijing genotype was strongly associated with rpsL43 mutation (aOR 23.6, 95%CI 2.9-193.4, P = 0.002). The median MIC for each mutation was as follows: rpsL43 = 256 μg/ml, rpsL88 = 16 μg/ml, 515 loop = 4 μg/ml, 910 region = 8 μg/ml, and double mutation = 256 μg/ml. We found a strong association between rpsL43 and high drug resistance levels, with all rpsL43 mutants having an MIC &gt;256 μg/ml (P &lt; 0.001).</abstract><cop>Paris, France</cop><pub>International Union Against Tuberculosis and Lung Disease</pub><pmid>22640514</pmid><doi>10.5588/ijtld.11.0202</doi><tpages>5</tpages></addata></record>
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subjects Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - pharmacology
Bacterial diseases
Bacterial Typing Techniques - methods
Beijing Genotype
Biological and medical sciences
Drug Resistance
Drug Resistance, Bacterial - genetics
Genotype
Human bacterial diseases
Humans
Infectious diseases
Medical sciences
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - isolation & purification
Pharmacology. Drug treatments
Pneumology
Respiratory system : syndromes and miscellaneous diseases
RNA, Bacterial
Sequence Analysis, RNA - methods
Streptomycin
Streptomycin - pharmacology
Tuberculosis
Tuberculosis and atypical mycobacterial infections
Tuberculosis, Multidrug-Resistant - diagnosis
Tuberculosis, Multidrug-Resistant - drug therapy
Tuberculosis, Multidrug-Resistant - microbiology
Vietnam
title Association of streptomycin resistance mutations with level of drug resistance and Mycobacterium tuberculosis genotypes
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