结核分枝杆菌耐氯法齐明相关基因研究进展
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摘要
目前,全球范围内结核病防控形势仍十分严峻,且耐药结核病所占比例较高,因此不断有新型抗结核病药物被研发出来并应用于临床。氯法齐明是目前世界卫生组织(WHO)推荐的二线核心抗结核药物之一,主要用于治疗耐多药结核病(MDR-TB)且疗效肯定,但近年来结核分枝杆菌对氯法齐明耐药现象增多。本文综述了结核分枝杆菌耐氯法齐明相关基因,旨在为结核分枝杆菌对氯法齐明的耐药机制研究提供参考。
Tuberculosis prevention and control situation is still serious all of the world at present,and proportion of drug resistant tuberculosis is relatively high,thus new anti-tuberculosis drugs are being continually developed and applied on clinic. Clofazimine is one of second-line core anti-tuberculosis drugs in treating MDR-TB recommended by WHO,but drug resistance to clofazimine gradually increased in recent years. This paper reviewed the drug resistance related genes of Mycobacterium tuberculosis to clofazimine,in order to provide a reference for the research on resistance mechanism to clofazimine.
Tuberculosis prevention and control situation is still serious all of the world at present,and proportion of drug resistant tuberculosis is relatively high,thus new anti-tuberculosis drugs are being continually developed and applied on clinic. Clofazimine is one of second-line core anti-tuberculosis drugs in treating MDR-TB recommended by WHO,but drug resistance to clofazimine gradually increased in recent years. This paper reviewed the drug resistance related genes of Mycobacterium tuberculosis to clofazimine,in order to provide a reference for the research on resistance mechanism to clofazimine.
引文
[1]World Health Organization.Global Tuberculosis Report 2018[R].Geneva:WHO,2018.
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[5]TYAGI S,AMMERMAN N C,LI S Y,et al.Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis[J].Proc Natl Acad Sci USA,2015,112(3):869-874.DOI:10.1073/pnas.1416951112.
[6]TASNEEN R,LI S Y,PELOQUIN C A,et al.Sterilizing activity of novel TMC207-and PA-824-containing regimens in a murine model of Tuberculosis[J].Antimicrob Agents Chemother,2011,55(12):5485-5492.DOI:10.1128/AAC.05293-11.
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[11]HARTKOORN R C,UPLEKAR S,COLE S T.Cross-Resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2014,58(5):2979-2981.DOI:10.1128/AAC.00037-14.
[12]CHOLO M C,STEEL H C,FOURIE P B,et al.Clofazimine:current status and future prospects[J].J Antimicrob Chemother,2012,67(2):290-298.DOI:10.1093/jac/dkr444.
[13]YANO T,KASSOVSKA-BRATINOVA S,TEH J S,et al.Reduction of clofazimine by mycobacterial type 2 NADH:quinone oxidoreductase a pathway for the generation of bactericidal levels of reactive oxygen species[J].J Biol Chem,2011,286(12):10276-10287.DOI:10.1074/jbc.M110.200501.
[14]CHOLO M C,BOSHOFF H I,STEEL H C,et al.Effects of clofazimine on potassium uptake by a Trk-deletion mutant of Mycobacterium tuberculosis[J].J Antimicrob Chemother,2006,57(1):79-84.
[15]RADHAKRISHNAN A,KUMAR N,WRIGHT C C,et al.Crystal Structure of the Transcriptional Regulator Rv0678 of Mycobacterium tuberculosis[J].J Biol Chem,2014,289(23):16526-16540.DOI:10.1074/jbc.M113.538959.
[16]ZHANG S,CHEN J,CUI P,et al.Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis[J].J Antimicrob Chemother,2015,70(9):2507-2510.DOI:10.1093/jac/dkv150.
[17]PANG Y,ZONG Z,HUO F,et al.In vitro Drug Susceptibility of Bedaquiline,Delamanid,Linezolid,Clofazimine,Moxifloxacin,and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing,China[J].Antimicrob Agents Chemother,2017,61(10).pii:e00900-17.DOI:10.1128/AAC.00900-17.
[18]ALMEIDA D,IOERGER T,TYAGI S,et al.Mutations in pepQConfer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2016,60(8):4590-4599.DOI:10.1128/AAC.00753-16.
[19]DOMENECH P,REED M B,BARRY C E 3rd.Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance[J].Infect Immun,2005,73(6):3492-3501.
[20]ANDRIES K,VILLELLAS C,COECK N,et al.Acquired resistance of Mycobacterium tuberculosis to bedaquiline[J].PloS One,2014,9(7):e102135.DOI:10.1371/journal.pone.0102135.
[21]GUPTA S,COHEN K A,WINGLEE K,et al.Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2014,58(1):574-576.DOI:10.1128/AAC.01462-13.
[22]SOMOSKOVI A,BRUDERER V,H?MKE R,et al.A mutation associated with clofazimine and bedaquiline cross-resistance in MDR-TB following bedaquiline treatment[J].Eur Respir J,2015,45(2):554-557.DOI:10.1183/09031936.00142914.
[23]MILANO A,PASCA M R,PROVVEDI R,et al.Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-MmpL5efflux system[J].Tuberculosis(Edinb),2009,89(1):84-90.DOI:10.1016/j.tube.2008.08.003.
[2]WILLIAMS K,MINKOWSKI A,AMOABENG O,et al.Sterilizing activities of novel combinations lacking first-and second-Line drugs in a murine model of tuberculosis[J].Antimicrob Agents Chemother,2012,56(6):3114-3120.DOI:10.1128/AAC.00384-12.
[3]ISLAM M M,HAMEED H M A,MUGWERU J,et al.Drug resistance mechanisms and novel drug targets for tuberculosis therapy[J].J Genet Genomics,2017,44(1):21-37.DOI:10.1016/j.jgg.2016.10.002.
[4]MOTHIBA M T,ANDERSON R,FOURIE B,et al.Effects of clofazimine on planktonic and biofilm growth of Mycobacterium tuberculosis and Mycobacterium smegmatis[J].J Glob Antimicrob Resist,2015,3(1):13-18.DOI:10.1016/j.jgar.2014.12.001.
[5]TYAGI S,AMMERMAN N C,LI S Y,et al.Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis[J].Proc Natl Acad Sci USA,2015,112(3):869-874.DOI:10.1073/pnas.1416951112.
[6]TASNEEN R,LI S Y,PELOQUIN C A,et al.Sterilizing activity of novel TMC207-and PA-824-containing regimens in a murine model of Tuberculosis[J].Antimicrob Agents Chemother,2011,55(12):5485-5492.DOI:10.1128/AAC.05293-11.
[7]VAN D A,MAUG A K,SALIM M A,et al.Short,highly effective,and inexpensive standardized treatment of multidrugresistant tuberculosis[J].Am J Respir Crit Care Med,2010,182(5):684-692.DOI:10.1164/rccm.201001-0077OC.
[8]MOORE V J.A review of side-effects experienced by patients taking clofazimine[J].Lepr Rev,1983,54(4):327-335.
[9]SILVA D R,DALCOLMO M,TIBERI S,et al.New and repurposed drugs to treat multidrug-and extensively drug-resistant tuberculosis[J].J Bras Pneumol,2018,44(2):153-160.DOI:10.1590/s1806-37562017000000436.
[10]GOPAL M,PADAYATCHI N,METCALFE J Z,et al.Systematic review of clofazimine for the treatment of drug-resistant tuberculosis[J].Int J Tuberc Lung Dis,2013,17(8):1001-1007.DOI:10.5588/ijtld.12.0144.
[11]HARTKOORN R C,UPLEKAR S,COLE S T.Cross-Resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2014,58(5):2979-2981.DOI:10.1128/AAC.00037-14.
[12]CHOLO M C,STEEL H C,FOURIE P B,et al.Clofazimine:current status and future prospects[J].J Antimicrob Chemother,2012,67(2):290-298.DOI:10.1093/jac/dkr444.
[13]YANO T,KASSOVSKA-BRATINOVA S,TEH J S,et al.Reduction of clofazimine by mycobacterial type 2 NADH:quinone oxidoreductase a pathway for the generation of bactericidal levels of reactive oxygen species[J].J Biol Chem,2011,286(12):10276-10287.DOI:10.1074/jbc.M110.200501.
[14]CHOLO M C,BOSHOFF H I,STEEL H C,et al.Effects of clofazimine on potassium uptake by a Trk-deletion mutant of Mycobacterium tuberculosis[J].J Antimicrob Chemother,2006,57(1):79-84.
[15]RADHAKRISHNAN A,KUMAR N,WRIGHT C C,et al.Crystal Structure of the Transcriptional Regulator Rv0678 of Mycobacterium tuberculosis[J].J Biol Chem,2014,289(23):16526-16540.DOI:10.1074/jbc.M113.538959.
[16]ZHANG S,CHEN J,CUI P,et al.Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis[J].J Antimicrob Chemother,2015,70(9):2507-2510.DOI:10.1093/jac/dkv150.
[17]PANG Y,ZONG Z,HUO F,et al.In vitro Drug Susceptibility of Bedaquiline,Delamanid,Linezolid,Clofazimine,Moxifloxacin,and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing,China[J].Antimicrob Agents Chemother,2017,61(10).pii:e00900-17.DOI:10.1128/AAC.00900-17.
[18]ALMEIDA D,IOERGER T,TYAGI S,et al.Mutations in pepQConfer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2016,60(8):4590-4599.DOI:10.1128/AAC.00753-16.
[19]DOMENECH P,REED M B,BARRY C E 3rd.Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance[J].Infect Immun,2005,73(6):3492-3501.
[20]ANDRIES K,VILLELLAS C,COECK N,et al.Acquired resistance of Mycobacterium tuberculosis to bedaquiline[J].PloS One,2014,9(7):e102135.DOI:10.1371/journal.pone.0102135.
[21]GUPTA S,COHEN K A,WINGLEE K,et al.Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis[J].Antimicrob Agents Chemother,2014,58(1):574-576.DOI:10.1128/AAC.01462-13.
[22]SOMOSKOVI A,BRUDERER V,H?MKE R,et al.A mutation associated with clofazimine and bedaquiline cross-resistance in MDR-TB following bedaquiline treatment[J].Eur Respir J,2015,45(2):554-557.DOI:10.1183/09031936.00142914.
[23]MILANO A,PASCA M R,PROVVEDI R,et al.Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-MmpL5efflux system[J].Tuberculosis(Edinb),2009,89(1):84-90.DOI:10.1016/j.tube.2008.08.003.