CAJ | 학술논문

目的了解结核分枝杆菌利福平/利福布丁交叉耐药株与利福平耐药/利福布丁敏感株rpoB全基因突变特征的差异.方法测定rpoB全基因序列,比较278株利福平/利福布丁交叉耐药(rifampicin/rifabutin cross-resistant,RIF/Rfb-R)株和40株利福平耐药/利福布丁敏感(rifampicinresistant/rifabutin-susceptible,RIF-R/Rfb-S)株,30株利福平/利福布丁敏感(rifampicin-susceptible/rifabutin-susceptible,RIF-S/Rfb-S)株及标准株H37 Rv之间的rpoB全基因序列突变差异.结果利福平/利福布丁敏感株和H37Rv rpoB全基因未发现突变；利福平/利福布丁交叉耐药株的常见突变位点是531(70.5％)和526( 20.9％).223( 80.2％)株单点突变株分别含有S531L、S531W、H526D、H526Y、H526R、Q513K、Q513P、Q510H、V176F、P287R、Y395C及H404Y单点突变,55( 19.8％)株多重突变株分别以S531L、H526R、H526Y、H526D、D516G和Q513K位点与其他位点联合突变为主.利福平耐药/利福布丁敏感株的常见突变位点分别是516(65.0％)、526( 17.5％)和533( 10.0％).21(52.5％)株单点突变株分别含有L533P、H526L、H526S、S522L、D516V、D516Y和D516F单点突变,19(47.5％)株多重突变株分别以D516V和L533P位点与其他位点联合突变为主.结论本批标本中,利福霉素耐药株rpoB基因突变率为100％,利福平/利福布丁交叉耐药株与利福平耐药/利福布丁敏感株rpoB全基因单点突变株的突变位置或氨基酸替换类型、多重突变株的突变位置或组合类型以及常见突变位点或其氨基酸替换类型完全不同,rpoB全基因DNA序列分析对临床科学应用利福平和利福布丁有指导意义.
목적 료해결핵분지간균리복평/리복포정교차내약주여리복평내약/리복포정민감주rpoB전기인돌변특정적차이.방법 측정rpoB전기인서렬,비교278주리복평/리복포정교차내약(rifampicin/rifabutin cross-resistant,RIF/Rfb-R)주화40주리복평내약/리복포정민감(rifampicinresistant/rifabutin-susceptible,RIF-R/Rfb-S)주,30주리복평/리복포정민감(rifampicin-susceptible/rifabutin-susceptible,RIF-S/Rfb-S)주급표준주H37 Rv지간적rpoB전기인서렬돌변차이.결과 리복평/리복포정민감주화H37Rv rpoB전기인미발현돌변；리복평/리복포정교차내약주적상견돌변위점시531(70.5％)화526( 20.9％).223( 80.2％)주단점돌변주분별함유S531L、S531W、H526D、H526Y、H526R、Q513K、Q513P、Q510H、V176F、P287R、Y395C급H404Y단점돌변,55( 19.8％)주다중돌변주분별이S531L、H526R、H526Y、H526D、D516G화Q513K위점여기타위점연합돌변위주.리복평내약/리복포정민감주적상견돌변위점분별시516(65.0％)、526( 17.5％)화533( 10.0％).21(52.5％)주단점돌변주분별함유L533P、H526L、H526S、S522L、D516V、D516Y화D516F단점돌변,19(47.5％)주다중돌변주분별이D516V화L533P위점여기타위점연합돌변위주.결론 본비표본중,리복매소내약주rpoB기인돌변솔위100％,리복평/리복포정교차내약주여리복평내약/리복포정민감주rpoB전기인단점돌변주적돌변위치혹안기산체환류형、다중돌변주적돌변위치혹조합류형이급상견돌변위점혹기안기산체환류형완전불동,rpoB전기인DNA서렬분석대림상과학응용리복평화리복포정유지도의의.
Objective To learn the rpoB mutation difference in rifampicin/rifabutin cross-resistant (RIF/Rfb-R) clinical isolates and in rifampicin-resistant/rifabutin-susceptible (RIF-R/Rbo-S) clinical isolates of Mycobacterium tuberculosis.Methods To sequence the full-length genome of rpoB gene,and analyze the rpoB full-length gene mutation differences in 278 RIF/Rfb-R clinical isolates,40 RIF-R/Rfb-S clinical isolates,30 rifampicin-susceptible/rifabutin-susceptible (RIF-S/Rfb-S) and in 1 reference strain ofH37Rv.Results No mutations of rpoB full-length gene were found in H37Rv reference strain and RIF-S/Rfb-S clinical isolates.In RIF/Rfb-R clinical isolates,531 (70.5％ ) and 526 (20.9％ ) were the most frequent mutation codons.223 (80.2％ ) isolates possesed single mutations as S531L,S531W,H526D,H526Y,H526R,Q513K,Q513P,Q510H,V176F,P287R,Y395C and H404Y.55 (19.8％) isolates had multiple mutations,and among these the S531L,H526 R,H526Y,H526D,D516G and Q513K were the main substitutions which were in combination with other points.In RIF-R/Rfb-S clinical isolates,516 (65.0％),526 ( 17.5％ ) and 533 ( 10.0％ ) were the most frequent mutation codons.21 (52.5％ ) isolates possesed single mutations as L533P,H526L,H526S,S522L,D516V,D516Y and D516F.19 (47.5％)isolates had multiple mutations and among these the D516V and L533P were the main substitutions which were in combination with other points.Condusions In our study,100％ rifamycin-resistant clinical isolates of Mycobacterium tuberculosis had rpoB mutations,but the mutations in RIF/Rfb-R clinical isolates were sharply different from RIF-R/Rfb-S clinical isolates in mutation positions or amino acids substitutions of single mutations strains,mutation positions or combination types and the most frequently mutation codons or amino acids substitutions of multiple mutations strains.Thus,DNA sequencing is instructive and meaningful to choose rifampicin or rifabutin for tuberculosis treatment.