Abstract:Acinetobacter baumannii (Ab) is an important pathogens responsible for hospital-acquired infections, it is the undoubtedly one of the most successful pathogens responsible for the patients with a defective or low immune system or the ill patients in the ICU. The mechanism of multidrug resistance of 1Ab is mainly related to the hydrolysis of ndogenous enzymes to antibiotics. The reduction of affinity of antibiotics to target caused by changes in the target of agents that under the regulate of the modified enzyme. Excretion of antibiotic mediated by over-expression of efflux pump and abnormal structure of cell wall porin. The reduction of antibiotic sensitivity mediated by membrane potential abnormality that caused by permeability defect of cytomembrane. Changes of antibiotic targets. The decrease of sensitivity of antibiotics to targets mediated by changes of cell wall composition. Drug resistance mediated by enzymes dysfunction and protein synthesis abnormality that caused by insertion or deletion of endogenous or exogenous genes. In the review, we summarize current studies that contribute to the mechanism of multidrug resistance in Ab by utilizing the mechanism of various antibiotics and the virulence factors of Ab.
穆鹏1 胡方芳2 袁军1,3▲. 鲍曼不动杆菌抗生素耐药机制研究进展[J]. 中国医药导报, 2019, 16(8): 47-50.
MU Peng1 HU Fangfang2 YUAN Jun1,3▲. Advances in the study of the mechanism of resistance of Acinetobacter baumannii to antibiotics. 中国医药导报, 2019, 16(8): 47-50.
[1] Yoon EJ,Courvalin P,Grillot-Courvalin C. RND-type efflux pumps in multidrug-resistant clinical isolates of Acinetobacter baumannii:major role for AdeABC overexpression and AdeRS mutations [J]. Antimicrob Agents Ch-emother,2013,57(7):2989-2995.
[2] Chen CH,Lin LC,Chang YJ,et al. Infection control programs and antibiotic control programs to limit transmission of multi-drug resistant Acinetobacter baumannii infections:evolution of old problems and new challenges for institutes [J]. Int J Envir on Res Public Health,2015,12(8):8871-8882.
[3] Lockhart SR,Abramson MA,Beekmann SE,et al. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004 [J]. J Clin Microbiol,2007, 45(10):3352-3359.
[4] Hu FP,Guo Y,Zhu DM,et al. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance,2005-2014 [J]. Clin Microbiol Infect,2016,22(Suppl):S9-S14.
[5] 习慧明,徐英春,朱德妹,等.2010年中国CHINET鲍曼不动杆菌耐药性监测[J].中国感染与化疗杂志,2012,12(2):98-104.
[6] Frye JG,Jackson CR. Genetic mechanisms of antimicrobial resistance identified in Salmonella enterica,Escherichia coli,and Enteroccocus spp isolated from US food animals [J]. Front Microbiol,2013,4(135):1-22.
[7] Aly MM,Abu Alsoud NM,Elrobh MS,et al. High prevalence of the PER-1 gene among carbapenem-resistant Acinetobacter baumannii in Riyadh,Saudi Arabia [J]. Eur J Clin Microbiol Infect Dis,2016,35(11):1759-1766.
[8] Davodian E,Sadeghifard N,Ghasemian A,et al. Presence of bla PER-1 and bla VEB-1 beta-lactamase genes among isolates of Pseudomonas aeruginosa from South West of Iran [J]. J Epidemiol Glob Health,2016,6(3):211-213.
[9] 姚建平,黄永茂.TEM型β-内酰胺酶的研究进展[J].中国感染与化疗杂志,2014,14(6):550-555.
[10] 谢潋滟,王晓丽,张芳芳,等.肠杆菌科细菌中PER型超广谱β-内酰胺酶的基因检测及遗传特征分析[J].上海交通大学学报:医学版,2015,35(4):494-499.
[11] Héritier C,Poirel L,Nordmann P. Cephalosporinase over-expression resulting from insertion of ISAba1 in Acinetobacter baumannii [J]. Clin Microbiol Infect,2006,12(2):123-130.
[12] 暴蓉,赵克斌,戎建荣,等.产AmpC酶鲍曼不动杆菌的耐药表型及基因型分析[J].中国药物与临床,2011,11(7):772-774.
[13] 王代荣,李曦,祝宏,等.外膜孔道蛋白38缺失引起鲍曼不动杆菌对β-内酰胺类抗菌药物敏感性降低的实验研究[J].检验医学,2016,31(3):224-227.
[14] Evans BA,Amyes SG. OXA β-lactamases [J]. Clin Microbiol Rev,2014,27(2):241-263.
[15] Mu X,Nakano R,Nakano A,et al. Loop-mediated isothermal amplification:Rapid and sensitive detection of the antibiotic resistance gene ISAba1-blaOXA-51-like in Acinetobacter Baumannii [J]. J Microbiol Methods,2016, 121(2):36-40.
[16] Bonnin RA,Poirel L,Nordmann P.New Delhi metallo-β-lactamase-producing Acinetobacter baumannii:a novel paradigm for spreading antibiotic resistance genes [J]. Future Microbiol,2014,9(1):33-41.
[17] Penwell WF,Shapiro AB,Giacobbe RA,et al. Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii [J]. Antimicrob Agents Chemother,2015,59(3):1680-1689.
[18] Gu DX,,Hu YJ,Zhou HW,et al. Substitutions of Ser83Leu in GyrA and Ser80Leu in ParC associated with quinolone resistance in Acinetobacter pittii [J]. Microb Drug Resist,2015,21(3):345-351.
[19] Higuchi S,Shikata M,Chiba M,et al. Characteristics of antibiotic resistance and sequence type of Acinetobacter baumannii clinical isolates in Japan and the antibacterial activity of DS-8587 [J]. J Infect Chemother,2014,20(4):256-261.
[20] Bhattacharyya T,Sharma A,Akhter J,et al. The small molecule IITR08027 restores the antibacterial activity of fluoroquinolones againstmultidrug-resistant Acinetobacter baumannii by efflux inhibition [J]. Int J Antimicrob Agents,2017,50(2):219-226.
[21] Upadhyay S,Khyriem AB,Bhattacharya P,et al. High-level aminoglycoside resistance in Acinetobacter baumannii recovered from Intensive Care Unit patients in Northeastern India [J]. Indian J Med Microbiol,2018,36(1):43-48.
[22] Strateva T,Markova B,Marteva-Proevska Y,et al. Wid-espread dissemination of multidrug-resistant Acinetobacter baumannii producing OXA-23 carbapenemase and ArmA 16S ribosomal RNA methylase in a Bulgarian university hospital [J]. Braz J Infect Dis,2012,16(3):307-310.
[23] 罗柳林,应春妹,倪培华,等.耐碳青霉烯类抗菌药物鲍曼不动杆菌膜蛋白机制研究[J].检验医学,2010,25(4):304-308.
[24] Arroyo LA,Herrera CM,Fernandez L,et al. The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17978 and clinical isolates through phosphoethanolamine modification of lipid A [J]. Antimicrob Agents Chemother,2011,55(8):3743-3751.
[25] Hood MI,Becker KW,Roux CM,et al. Genetic determinants of intrinsic colistin tolerance in Acinetobacter baumannii [J]. Infect Immun,2013,81(2):542-551.
[26] Moffatt H,Harper M. Insertion sequence ISAba11 is involved in colistin resistance and loss of lipopolysaccharide in Acinetobacter baumannii [J]. Antimicrob Agents Chemother,2011,55(6):3022-3024.
[27] Llobet E,Tomás JM,Bengoechea JA. Capsule polysaccharide is a bacterial decoy for antimicrobial peptides [J]. Microbiology,2008,154(12):3877-3886.
[28] Geisinger E,Isberg RR. Antibiotic modulation of capsular exopolysaccharide and virulence in Acinetobacter baumannii [J]. PLoS Pathog,2015,11(2):e1004691.
[29] Tapas B,Atin S,Jawed A,et al. The small molecule IITR-08027 restores the antibacterial Activity of fluoroquin-olones againstmultidrug-resistant Acinetobacter baumannii by efflux inhibition [J]. Int J Antimicrob Agents,2017, 50(2):219-226.
[30] Li XZ, Plesiat P, Nikaido H. The challenge of effluxmediated antibiotic resistance in Gram-negative bacteria [J]. Clin Microbiol Rev,2015,28(2):337-418.
[31] Poirel L,Nordmann P. Carbapenem resistance in Acinetobacter baumannii:mechanisms and epidemiology [J]. Clin Microbiol Infect,2006,12(9):826-836.
[32] Li X,Quan J,Yang Y,et al. Abrp,a new gene,confers reduced susceptibility to tetracycline,glycylcine,chloramphenicol and fosfomycin classes in Acinetobacter baumannii [J]. Eur J Clin Microbiol Infect Dis,2016,35(8):1371-1375.
[33] 张驰,杨羚,凌保东.鲍曼不动杆菌8种RND外排泵介导替加环素耐药表型的研究[J].中国抗生素杂志,2018, 43(2):115-120.