整合子相关的DfrB4是三甲氧苄氨嘧啶耐药二氢叶酸还原酶B家族中一个先前未被描述的成员，是临床上已确认的抗生素耐药性新来源。
Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance.
作者信息
Toulouse Jacynthe L, Edens Thaddeus J, Alejaldre Lorea, Manges Amee R, Pelletier Joelle N
机构信息
Département de biochimie, Université de Montréal, C.P. 6128,Succursale Centre-ville, Montréal, Québec, Canada.
CGCC, Center in Green Chemistry and Catalysis, Montréal, Québec, Canada.
出版信息
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02665-16. Print 2017 May.
Abstract
Whole-genome sequencing of trimethoprim-resistant clinical isolates identified a member of the trimethoprim-resistant type II dihydrofolate reductase gene family (). The gene was located within a class I integron flanked by multiple resistance genes. This arrangement was previously reported in a 130.6-kb multiresistance plasmid. The DfrB4 protein conferred a >2,000-fold increased trimethoprim resistance on overexpression in Our results are consistent with the finding that contributes to clinical trimethoprim resistance.
摘要
对耐甲氧苄啶临床分离株进行全基因组测序，鉴定出一个耐甲氧苄啶的II型二氢叶酸还原酶基因家族成员（）。该基因位于一个由多个耐药基因侧翼的I类整合子内。这种排列先前在一个130.6 kb的多耐药质粒中已有报道。在 中过表达时，DfrB4蛋白使甲氧苄啶耐药性增加了2000倍以上。我们的结果与 导致临床甲氧苄啶耐药性的发现一致。
相似文献
1
Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance.
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02665-16. Print 2017 May.
2
New integron-associated gene cassette encoding a trimethoprim-resistant DfrB-type dihydrofolate reductase.
Antimicrob Agents Chemother. 2006 Aug;50(8):2863-5. doi: 10.1128/AAC.00449-06.
3
Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use.
PLoS One. 2010 Feb 16;5(2):e9233. doi: 10.1371/journal.pone.0009233.
4
The prevalence of trimethoprim-resistance-conferring dihydrofolate reductase genes in urinary isolates of Escherichia coli in Korea.
J Antimicrob Chemother. 2001 May;47(5):599-604. doi: 10.1093/jac/47.5.599.
5
Prevalence of dfr genes associated with integrons and dissemination of dfrA17 among urinary isolates of Escherichia coli in Korea.
J Antimicrob Chemother. 2004 Mar;53(3):445-50. doi: 10.1093/jac/dkh097. Epub 2004 Feb 12.
6
pCERC3 from a commensal ST95 Escherichia coli: A ColV virulence-multiresistance plasmid carrying a sul3-associated class 1 integron.
Plasmid. 2016 Mar-May;84-85:11-9. doi: 10.1016/j.plasmid.2016.02.002. Epub 2016 Feb 18.
7
Two new gene cassettes, dfr17 (for trimethoprim resistance) and aadA4 (for spectinomycin/streptomycin resistance), inserted in an Escherichia coli class 1 integron.
J Antimicrob Chemother. 2000 Jul;46(1):87-9. doi: 10.1093/jac/46.1.87.
8
New dfr2 gene as a single-gene cassette in a class 1 integron from a trimethoprim-resistant Escherichia coli isolate.
Microb Drug Resist. 2003 Winter;9(4):317-22. doi: 10.1089/107662903322762734.
9
New gene cassettes for trimethoprim resistance, dfr13, and Streptomycin-spectinomycin resistance, aadA4, inserted on a class 1 integron.
Antimicrob Agents Chemother. 2000 Feb;44(2):355-61. doi: 10.1128/AAC.44.2.355-361.2000.
10
The induction of trimethoprim resistance encoded by the type IV dihydrofolate reductase gene.
J Med Microbiol. 1993 Apr;38(4):256-61. doi: 10.1099/00222615-38-4-256.
引用本文的文献
1
Dominance of sequence types ST73, ST95, ST127 and ST131 in Australian urine isolates: a genomic analysis of antimicrobial resistance and virulence linked to F plasmids.
Microb Genom. 2023 Jul;9(7). doi: 10.1099/mgen.0.001068.
2
Trimethoprim resistance in surface and wastewater is mediated by contrasting variants of the dfrB gene.
ISME J. 2023 Sep;17(9):1455-1466. doi: 10.1038/s41396-023-01460-7. Epub 2023 Jun 27.
3
Epistasis between promoter activity and coding mutations shapes gene evolvability.
Sci Adv. 2023 Feb 3;9(5):eadd9109. doi: 10.1126/sciadv.add9109.
4
Discovery of Highly Trimethoprim-Resistant DfrB Dihydrofolate Reductases in Diverse Environmental Settings Suggests an Evolutionary Advantage Unrelated to Antibiotic Resistance.
Antibiotics (Basel). 2022 Dec 7;11(12):1768. doi: 10.3390/antibiotics11121768.
5
Antibiotic Resistance Genes in River Biofilms: A Metagenomic Approach toward the Identification of Sources and Candidate Hosts.
Environ Sci Technol. 2022 Nov 1;56(21):14913-14922. doi: 10.1021/acs.est.2c00370. Epub 2022 Apr 25.
6
Development of antibacterial compounds that constrain evolutionary pathways to resistance.
Elife. 2021 Jul 19;10:e64518. doi: 10.7554/eLife.64518.
7
The Bacterial Genomic Context of Highly Trimethoprim-Resistant DfrB Dihydrofolate Reductases Highlights an Emerging Threat to Public Health.
Antibiotics (Basel). 2021 Apr 13;10(4):433. doi: 10.3390/antibiotics10040433.
8
Dual-Target Inhibitors of the Folate Pathway Inhibit Intrinsically Trimethoprim-Resistant DfrB Dihydrofolate Reductases.
ACS Med Chem Lett. 2020 Sep 28;11(11):2261-2267. doi: 10.1021/acsmedchemlett.0c00393. eCollection 2020 Nov 12.
9
Genomic analysis of trimethoprim-resistant extraintestinal pathogenic and recurrent urinary tract infections.
Microb Genom. 2020 Dec;6(12). doi: 10.1099/mgen.0.000475. Epub 2020 Nov 18.
10
Exploration into the origins and mobilization of di-hydrofolate reductase genes and the emergence of clinical resistance to trimethoprim.
Microb Genom. 2020 Nov;6(11). doi: 10.1099/mgen.0.000440.
本文引用的文献
1
Complete Genome Sequence of a CTX-M-15-Producing Escherichia coli Strain from the H30Rx Subclone of Sequence Type 131 from a Patient with Recurrent Urinary Tract Infections, Closely Related to a Lethal Urosepsis Isolate from the Patient's Sister.
Genome Announc. 2016 May 12;4(3):e00334-16. doi: 10.1128/genomeA.00334-16.
2
Tales of Dihydrofolate Binding to R67 Dihydrofolate Reductase.
Biochemistry. 2016 Jan 12;55(1):133-45. doi: 10.1021/acs.biochem.5b00981. Epub 2015 Dec 21.
3
15N, 13C and 1H backbone resonance assignments of an artificially engineered TEM-1/PSE-4 class A β-lactamase chimera and its deconvoluted mutant.
Biomol NMR Assign. 2016 Apr;10(1):93-9. doi: 10.1007/s12104-015-9645-8. Epub 2015 Sep 19.
4
MOLECULAR DETECTION OF ANTIBIOTIC-RESISTANCE DETERMINANTS IN ESCHERICHIA COLI ISOLATED FROM THE ENDANGERED AUSTRALIAN SEA LION (NEOPHOCA CINEREA).
J Wildl Dis. 2015 Jul;51(3):555-63. doi: 10.7589/2014-08-200. Epub 2015 Apr 28.
5
Large-scale genomic sequencing of extraintestinal pathogenic Escherichia coli strains.
Genome Res. 2015 Jan;25(1):119-28. doi: 10.1101/gr.180190.114. Epub 2014 Nov 4.
6
Integrons: past, present, and future.
Microbiol Mol Biol Rev. 2014 Jun;78(2):257-77. doi: 10.1128/MMBR.00056-13.
7
Fragment-based design of symmetrical bis-benzimidazoles as selective inhibitors of the trimethoprim-resistant, type II R67 dihydrofolate reductase.
J Med Chem. 2012 Apr 12;55(7):3182-92. doi: 10.1021/jm201645r. Epub 2012 Mar 28.
8
GenBank.
Nucleic Acids Res. 2012 Jan;40(Database issue):D48-53. doi: 10.1093/nar/gkr1202. Epub 2011 Dec 5.
9
Chromate-resistance genes in plasmids from antibiotic-resistant nosocomial enterobacterial isolates.
FEMS Microbiol Lett. 2012 Feb;327(2):148-54. doi: 10.1111/j.1574-6968.2011.02473.x. Epub 2011 Dec 16.
10
Novel crystallization conditions for tandem variant R67 DHFR yield a wild-type crystal structure.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Nov 1;67(Pt 11):1316-22. doi: 10.1107/S1744309111030417. Epub 2011 Oct 25.
Zotero 插件