替加环素耐药机制研究进展

doi:10.16431/j.cnki.1671-7236.2020.09.038

Abstract

Abstract: Tigecycline,as a new tetracycline antibiotic,is one of the last lines of defense against carbapenems-producing enterobacter multidrug-resistant infections.In recent years,the emergence of tigecycline-resistant strains has severely restricted the clinical use of tigecycline.It was originally believed that the resistance mechanism of tigecycline was mediated by the efflux pump encoded by the chromosome,which could not lead to drug resistance by horizontal transfer.With the deepening of research,it was found that some efflux pump mutations or high expression on the plasmid could also cause the strain's tigecycline sensitivity to decrease.Recently,it has been reported that the plasmid-mediated tet(X) variant can make the strain highly resistant to tigecycline,and can be spread among different species of bacteria through adaptable plasmids.This article described the prevalence and transmission mechanism of high-level tigecycline resistance gene tet(X) variants by introducing bacterial chromosome-mediated tigecycline resistance mechanisms and plasmid-mediated tigecycline resistance mechanisms,and provided a reasonable explanation for the high-level variant of the tigecycline resistance gene tet(X) in animal-derived strains,aiming to provide reference for relevant scientific researchers and clinical workers.

Key words: tigecycline; resistance mechanism; efflux pump; plasmid; tet(X) variations

CLC Number:

S852.6

WANG Liangliang, WANG Qianqian, ZHOU Bolun, JIA Yixin, WU Hua, YUAN Li, HU Gongzheng, HE Dandan. Advance on the Tigecycline Resistance Mechanism[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(9): 3022-3029.

References

[1] CHOPRA I.Glycylcyclines:Third-generation tetracycline antibiotics[J].Current Opinion in Pharmacology,2001,1(5):464-469.
[2] LIVERMORE D M.Tigecycline:What is it,and where should it be used?[J].Journal of Antimicrobial Chemotherapy, 2005,56(4):611-614.
[3] BRADFORD P A.Tigecycline:A first in class glycylcycline[J].Clinical Microbiology Newsletter,2004,26(21):163-168.
[4] HE T,WANG R,LIU D,et al.Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans[J].Nature Microbiology,2019,4(9):1450-1456.
[5] 胡超,赵子文.多重耐药鲍曼不动杆菌耐药机制及治疗进展[J].广东医学,2015,36(12):1803-1806. HU C,ZHAO Z W.Mechanism and treatment progress of multiple drug resistance Acinetobacter baumannii[J].Guangdong Medical,2015,36(12):1803-1806.(in Chinese)
[6] 徐婷,金顺鑫,王潇,等.细菌外排泵系统acrAB-tolC的研究进展[J].黑龙江畜牧兽医,2016,9:92-95. XU T,JIN S X,WANG X,et al.Research progress of acrAB-tolC in bacterial efflux pump system[J].Heilongjiang Animal Science and Veterinary Medicine,2016,9:92-95.(in Chinese)
[7] BREEDT J,TERAS J,GARDOVSKIS J,et al.Safety and efficacy of tigecycline in treatment of skin and skin structure infections:Results of a double-blind phase 3 comparison study with vancomycin-aztreonam[J].Antimicrobial Agents and Chemotherapy,2005,49(11):4658-4666.
[8] DAUREL C,FIANT A L,BRÉMONT S,et al.Emergence of an Enterobacter hormaechei strain with reduced susceptibility to tigecycline under tigecycline therapy[J].Antimicrobial Agents and Chemotherapy,2009,53(11):4953-4954.
[9] HOBAN D J,BOUCHILLON S K,JOHNSON B M,et al.In vitro activity of tigecycline against 6792 Gram-negative and Gram-positive clinical isolates from the global tigecycline evaluation and surveillance trial (TEST Program,2004)[J].Diagnostic Micro-biology and Infectious Disease,2005,52(3):215-227.
[10] KEENEY D,RUZIN A,MCALEESE F,et al.MarA-mediated overexpression of the AcrAB efflux pump results in decreased susceptibility to tigecycline in Escherichia coli[J].Journal of Antimicrobial Chemo-therapy,2008,61(1):46-53.
[11] JENNER L,STAROSTA A L,TERRY D S,et al.Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis[J].Proceedings of the National Academy of Sciences of the United States America,2013,110(10):3812-3816.
[12] RUZIN A,VISALLI M A,KEENEY D,et al.Influence of transcriptional activator RamA on expression of multidrug efflux pump AcrAB and tigecycline susceptibility in Klebsiella pneumoniae[J].Antimicrobial Agents and Chemotherapy,2005,49(3):1017-1022.
[13] KEENEY D,RUZIN A,BRADFORD P A.RamA,a transcriptional regulator,and AcrAB,an RND-type efflux pump,are associated with decreased susceptibi-lity to tigecycline in Enterobacter cloacae[J].Microbial Drug Resistance,2007,13(1):1-6.
[14] BRATU S,LANDMAN D,GEORGE A,et al.Correlation of the expression of acrB and the regulatory genes marA,soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York city[J].The Journal of Antimicrobial Chemotherapy,2009,64(2):278-283.
[15] YE M P,DING B X,QIAN H L,et al.In vivo development of tigecycline resistance in Klebsiella pneumoniae owing to deletion of the ramR ribosomal binding site[J].International Journal of Antimicrobial Agents,2017,50(4):523-528.
[16] CHEN J,KURODA T,HUDA M N,et al.An RND-type multidrug efflux pump SdeXY from Serratia marcescens[J].The Journal of Antimicrobial Chemo-therapy,2003,52(2):176-179.
[17] HORNSEY M,ELLINGTON M J,DOUMITH M,et al.Tigecycline resistance in Serratia marcescens associated with up-regulation of the SdeXY-HasF efflux system also active against ciprofloxacin and cefpirome[J].The Journal of Antimicrobial Chemo-therapy,2010,65(3):479-482.
[18] JUAN C H,HUANG Y W,LIN Y T,et al.Risk factors,outcomes,and mechanisms of tigecycline-nonsusceptible Klebsiella pneumoniae bacteremia[J].Antimicrobial Agents and Chemotherapy,2016,60(12):7357-7363.
[19] KIM H B,WANG M,PARK C H,et al.oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae[J].Antimicrobial Agents and Chemotherapy,2009,53(8):3582-3584.
[20] LIN Y T,HUANG Y W,HUANG H H,et al. In vivo evolution of tigecycline-non-susceptible Klebsiella pneumoniae strains in patients:Relationship between virulence and resistance[J].International Journal of Antimicrobial Agents,2016,48(5):485-491.
[21] SHENG Z K,HU F P,WANG W X,et al.Mechanisms of tigecycline resistance among Klebsiella pneumoniae clinical isolates[J].Antimicrobial Agents and Chemotherapy,2014,58(11):6982-6985.
[22] ZHONG X,XU H,CHEN D,et al.First emergence of acrAB and oqxAB mediated tigecycline resistance in clinical isolates of Klebsiella pneumoniae pre-dating the use of tigecycline in a Chinese hospital[J].PLoS One,2014,9(12):e115185.
[23] LV L,WAN M,WANG C,et al.Emergence of a plasmid-encoded resistance-nodulation-division efflux pump conferring resistance to multiple drugs,including tigecycline,in Klebsiella pneumoniae[J].mBio,2020,11(2):e02930-19.
[24] TUCKMAN M,PETERSEN P J,PROJAN S J.Mutations in the interdomain loop region of the tetA(A) tetracycline resistance gene increase efflux of minocycline and glycylcyclines[J].Microbial Drug Resistance (Larchmornt N.Y.),2000,6(4):277-282.
[25] HENTSCHKE M,CHRISTNER M,SOBOTTKA I,et al.Combined ramR mutation and presence of a Tn1721-associated tet(A) variant in a clinical isolate of Salmonella enterica serovar Hadar resistant to tigecycline[J].Antimicrobial Agents and Chemotherapy,2010,54(3):1319-1322.
[26] YAO H,QIN S S,CHEN S,et al.Emergence of carbapenem-resistant hypervirulent Klebsiella pneumo-niae[J].The Lancet.Infectious Diseases,2018,18(1):25.
[27] GUINEY J D G,HASEGAWA P,DAVIS C E.Expression in Escherichia coli of cryptic tetracycline resistance genes from Bacteroides R plasmids[J].Plasmid,1984,11(3):248-252.
[28] WHITTLE G,HUND B D,SHOEMAKER N B,et al.Characterization of the 13-kilobase ermF region of the Bacteroides conjugative transposon CTnDOT[J].Applied and Environmental Microbiology,2001,67(8):3488-3495.
[29] LESKI T A,BANGURA U,JIMMY D H,et al.Multidrug-resistant tet(X)-containing hospital isolates in Sierra Leone[J].International Journal of Antimicrobial Agents,2013,42(1):83-86.
[30] LI R,LIU Z,PENG K,et al.Co-occurrence of two tet(X) variants in an Empedobacter brevis of shrimp origin[J].Antimicrobial Agents and Chemotherapy,2019:e0136-19.
[31] WANG L,LIU D,LV Y,et al.Novel plasmid-mediated tet(X5) gene conferring resistance to tigecycline,eravacycline,and omadacycline in a clinical Acinetobacter baumannii isolate[J].Antimicrobial Agents and Chemotherapy,2019,64(1):e01326-19.
[32] HE D,WANG L,ZHAO S,et al.A novel tigecycline resistance gene,tet(X6),on an SXT/R391 integrative and conjugative element in a Proteus genomospecies 6 isolate of retail meat origin[J].Journal of Antimicro-bial Chemotherapy,2020,75(5):1159-1164.
[33] HE T,WEI R C,LI R C,et al.Co-existence of tet(X4) and mcr-1 in two porcine Escherichia coli isolates[J].Journal of Antimicrobial Chemotherapy,2020,75(3):764-766.
[34] SUN J,CHEN C,CUI C Y,et al.Plasmid-encoded tet(X) genes that confer high-level tigecycline resistance in Escherichia coli[J].Nature Microbiology,2019,4(9):1457-1464.
[35] CUI C Y,CHEN C,LIU B T,et al.Co-occurrence of plasmid-mediated tigecycline and carbapenem resistance in Acinetobacter spp. from waterfowls and their neighboring environment[J].Antimicrobial Agents and Chemotherapy,2020,64(5):e02502-19.
[36] SUN C,CUI M,ZHANG S,et al.Plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from food-producing animals,China,2008-2018[J].Emerging Microbes & Infections,2019,8(1):1524-1527.
[37] ZHANG Q Q,YING G G,PAN C G,et al.Comprehensive evaluation of antibiotics emission and fate in the river basins of China:Source analysis,multimedia modeling,and linkage to bacterial resistance[J].Environmental Science & Technology,2015,49(11):6772-6782.
[38] CAO J,WANG J,WANG Y,et al.Tigecycline resistance tet(X3) gene is going wild[J].Biosafety and Health,2020,2(1):9-11.
[39] CHEN C,CUI C Y,ZHANG Y,et al.Emergence of mobile tigecycline resistance mechanism in Escherichia coli strains from migratory birds in China[J].Emerging Microbes & Infections,2019,8(1):1219-1222.
[40] BAI L,DU P,DU Y,et al.Detection of plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from pork,Sichuan and Shandong provinces,China,February 2019[J].Eurosurveillance,2019,24(25):1900340.
[41] CHEN C,WU X T,HE Q,et al.Complete sequence of a tet(X4)-harboring IncX1 plasmid,pYY76-1-2,in Escherichia coli from a cattle sample in China[J].Antimicrobial Agents and Chemotherapy,2019,63(12):e01528-19.
[42] FANG L X,CHEN C,YU D L,et al.Complete nucleotide sequence of a novel plasmid bearing the high-level tigecycline resistance gene tet(X4)[J].Antimicrobial Agents and Chemotherapy,2019,63(11):e01373-19.
[43] CHEN C,CHEN L,ZHANG Y,et al.Detection of chromosome-mediated tet(X4)-carrying Aeromonas caviae in a sewage sample from a chicken farm[J].Journal of Antimicrobial Chemotherapy,2019,74(12):3628-3630.

Advance on the Tigecycline Resistance Mechanism

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	SUN Haifeng, TAN Aijuan, LYU Shiming, LUO Yujia, JI Qiqi, AI Renli, LU Xingxing, FENG Dan. Effect of Hypertonicity on Gene Expression of Efflux Pump and Outer Membrane Protein in Multidrug Resistant Escherichia coli and Its Growth [J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(9): 3473-3482.
[2]	YUAN Weiyi, LIN Xiaofeng, ZHANG Yuhao, XIAO Jinnan, WANG Yan. Research Progress on Antimicrobial and Disinfectant Resistance of Methicillin-resistant Staphylococcus pseudintermedius in Canine Pyoderma [J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(9): 3483-3490.
[3]	ZOU Juhong, SHEN Yujian, GAO Xiaotong, HUANG Yanna, JIANG Qinyang. Cloning and Analysis of FTO Gene of Nubian Goat and Construction of Eukaryotic Expression Vector [J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(7): 2342-2348.
[4]	CHEN Jiali, CHEN Chaoqun, WU Xue, HUANG Anxiong, HAO Haihong. Establishment of the Epidemiological Cut-off Values of Haemophilus parasuis for Quinolones [J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(11): 4292-4301.
[5]	LI Jie, CHEN Jing, YANG Fan, LI Jun, CAI Yafei. Construction and Identification of Lentiviral Overexpression Plasmid of Mouse Zbtb38 Gene [J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(10): 3088-3094.
[6]	ZHU Chen, CAO Shuyang, WU Zhihao, YIN Jun, ZHU Liqi, ZHANG Quan. Construction and Identification of Helicobacter hepaticus CdtB Gene Mutant Strain [J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(1): 1-7.
[7]	ZHOU Yi, WANG Bolin, YANG Mei, HE Ling, QIN Lan, YUE Jun, ZHANG Shuangxiang, ZHOU Bijun, WANG Kaigong, CHENG Zhentao. Construction of Mycoplasma ovipneumoniae pcDNA3.1-TBP30-Hsp70 Fusion Plasmid and Its Effect on Cellular Immune Response in Mice [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(11): 3387-3395.
[8]	LUO Cheng, QI Jiangjiao, WANG Yuanyuan, GAO Jianfeng. Construction of Red Fluorescent Protein Expression Vector of Brucella Using Overlapping Extension PCR Method [J]. , 2018, 45(9): 2394-2400.
[9]	ZHAO Yun, WU Shengjun, NI Tingting, WANG Miao, ZHANG Shoufa, XU Yingtian, XUE Shujiang. Construction and Immunological Effect Analysis of Plasmid DNA Expressing ENO Gene of Mycoplasma suis [J]. , 2018, 45(9): 2559-2565.
[10]	WANG Miao, NI Tingting, WU Shengjun, ZHAO Yun, SONG Jianchen, DONG Liang, XUE Shujiang. Construction and Eukaryotic Expression of Recombinant Adenovirus Shuttle Plasmid of Mycoplasma suis ENO Gene [J]. , 2018, 45(8): 2113-2118.
[11]	LIU Yong-an, LI Xue-rui, LIU Yong-sheng. Research Progress on Resistance Mechanisms and Detecting Technology of Mycobacterium tuberculosis [J]. , 2017, 44(6): 1884-1889.
[12]	HUA Wei-yi, CHEN Xiao-jie, LIU Yi-ming, XU Fei, LI Xiu-bo. Research Progress on Main Pathogen Resistance of Dairy Cows and Control Technology [J]. , 2017, 44(12): 3634-3641.
[13]	LUO Shuang, SUN Li-hong, Siriguleng, YAO Hong-qiang. JSRV-Env Recombinant Plasmid Induced-transfection of TC-1 and TC-1-Hyal2 and Influence of Cytokine VEGF and TGF-α [J]. , 2016, 43(9): 2215-2222.
[14]	ZHANG Ji-kai, SUN En-cheng, YANG Tao, XU Qing-yuan, LV Shuang, WANG Hai-xiu, ZHANG Qin, WU Dong-lai. Construction and Identification of Yeast Two-hybrid Bait Plasmids of Capsid Proteins VP2, VP5 and VP7 of Bluetongue Virus [J]. , 2016, 43(1): 39-44.
[15]	ZHANG Xiao-dan, GAO Li-li, HU Jia-qing, AI Wen-hao, CHAI Tong-jie. Study on Aerotransmission of Escherichia coli Carrying the Plasmid-mediated Quinolone Resistance Genes of Swine [J]. , 2015, 42(7): 1842-1850.