群体感应系统信号分子受体abaR基因对鲍曼不动杆菌致病性和获得性耐药的影响

廖佳馨, 胡韦维

PDF(1593 KB)
PDF(1593 KB)
重庆医科大学学报 ›› 2025, Vol. 50 ›› Issue (01) : 52-57. DOI: 10.13406/j.cnki.cyxb.003634

群体感应系统信号分子受体abaR基因对鲍曼不动杆菌致病性和获得性耐药的影响

作者信息 +
History +

摘要

目的 探讨群体感应系统(quorum sensing system,QS)信号分子受体abaR对鲍曼不动杆菌致病性和耐药性的影响。 方法 构建鲍曼不动杆菌ATCC 17978 abaR敲除株(ΔabaR),通过生长曲线分析、血清杀伤实验和生物膜形成实验,比较野生株和敲除株在生长速率、血清杀伤能力和生物膜形成能力等方面的差异;通过多步骤稳态体外诱导耐药实验,检测野生株ATCC 17978和敲除株ΔabaR诱导耐药后相关耐药基因表达水平的差异。 结果 生长曲线显示,野生株和敲除株在各个时期的600 nm处测定吸光度(absorbance,A)值无明显差异(t=10.720,P>0.05);血清杀伤实验表明,敲除株的健康人血清(normal human serum,NHS)/磷酸缓冲盐溶液(phosphate buffered saline,PBS)比值明显低于野生株(t=3.968,P<0.05);生物膜形成实验显示,敲除株的生物膜形成能力在培养的前24 h低于野生株(t=4.632,P<0.01);在体外将野生株和敲除株诱导为美罗培南耐药菌株后,敲除株的耐药基因AdeAAdeBAmpC表达水平低于野生株(t1=11.330;t2=15.010;t3=13.420,均P<0.001)。 结论 abaR基因通过调控生物膜形成和外排泵基因的表达,明显影响鲍曼不动杆菌的毒力和获得性耐药;干扰群体感应系统中的abaR受体分子可能是抑制群体感应信号和解决鲍曼不动杆菌耐药性问题的有效策略,为开发新型抗生素治疗耐药菌株奠定了基础。

Abstract

Objective To investigate the effect of the quorum sensing(QS) system LuxR type regulator abaR on the pathogenicity and drug resistance of Acinetobacter baumannii. Methods The abaR-knockout(ΔabaR) strain of A. baumannii ATCC 17978 was constructed,and the growth curve analysis,serum killing experiment,and biofilm formation assay were used to compare the wild strain and the ΔabaR strain in terms of growth rate and serum killing ability. The multi-step in vitro drug resistance induction test was used to investigate the differences in the expression levels of related drug resistance genes after induction of drug resistance between the ATCC 17978 wild strain and the ΔabaR strain. Results The growth curve showed that there was no significant difference in A600 nm value between the wild strain and the ΔabaR strain at each time point(t=10.720,P>0.05). The serum killing experiment showed that the ΔabaR strain had a significantly lower normal human serum/phosphate buffered saline(NHS/PBS) ratio than the wild strain(t=3.968,P<0.05). The biofilm formation assay showed that the ΔabaR strain had a significantly lower biofilm formation ability than the wild strain within the first 24 hours of culture(t=4.632,P<0.01). After the wild strain and the ΔabaR strain were induced to meropenem-resistant strains in vitro,compared with the wild strain,the ΔabaR strain had significantly lower expression levels of the drug-resistance genes AdeAAdeB,and AmpCt1=11.330;t2=15.010;t3=13.420,P<0.001). Conclusion The abaR gene significantly influences the virulence and acquired resistance of A. baumannii by regulating biofilm formation and the expression of efflux pump genes. Interference with the abaR receptor molecule within the QS may be an effective strategy to inhibit QS signaling and address the drug resistance of A. baumannii,which lays a foundation for developing novel antibiotics for the treatment of drug-resistant strains.

关键词

鲍曼不动杆菌 / abaR基因 / 毒力 / 生物被膜 / 获得性耐药

Key words

Acinetobacter baumannii / abaR gene / virulence / biofilm / acquired drug resistance

中图分类号

R378.99

引用本文

导出引用
廖佳馨 , 胡韦维. 群体感应系统信号分子受体abaR基因对鲍曼不动杆菌致病性和获得性耐药的影响. 重庆医科大学学报. 2025, 50(01): 52-57 https://doi.org/10.13406/j.cnki.cyxb.003634

参考文献

1
Zhao X Wang LH Wei N,et al. Epidemiological and clinical characteristics of healthcare-associated infection in elderly patients in a large Chinese tertiary hospital:a 3-year surveillance study[J]. BMC Infect Dis202020(1):121.
2
Jain M Sharma A Sen MK,et al. Phenotypic and molecular characterization of Acinetobacter baumannii isolates causing lower respiratory infections among ICU patients[J]. Microb Pathog2019128:75-81.
3
Li WB Liu CJ Ho HC,et al. Association between antibiotic resistance and increasing ambient temperature in China:an ecological study with nationwide panel data[J]. Lancet Reg Health West Pac202330:100628.
4
Tacconelli E Carrara E Savoldi A,et al. Discovery,research,and development of new antibiotics:the WHO priority list of antibiotic-resistant bacteria and tuberculosis[J]. Lancet Infect Dis201818(3):318-327.
5
Teerawattanapong N Panich P Kulpokin D,et al. A systematic review of the burden of multidrug-resistant healthcare-associated infections among intensive care unit patients in Southeast Asia:the Rise of multidrug-resistant Acinetobacter baumannii [J]. Infect Control Hosp Epidemiol201839(5):525-533.
6
Morikane K Suzuki S Yoshioka J,et al. Clinical and microbiological effect of pulsed xenon ultraviolet disinfection to reduce multidrug-resistant organisms in the intensive care unit in a Japanese hospital:a before-after study[J]. BMC Infect Dis202020(1):82.
7
Khan AU Maryam L Zarrilli R. Structure,Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase(NDM):a threat to public health[J]. BMC Microbiol201717(1):101.
8
Zhu LJ Chen XY Hou PF. Mutation of CarO participates in drug resistance in imipenem-resistant Acinetobacter baumannii [J]. J Clin Lab Anal201933(8):e22976.
9
戚丽华. 鲍曼不动杆菌耐药特性及其与生物膜的相关性研究[D]. 北京:中国人民解放军军事医学科学院,2016.
Qi LH. Study on drug resistance characteristics of Acinetobacter baumannii and its correlation with biofilm[D]. Beijing:PLA Academy of Military Medical Sciences,2016.
10
Amin M Navidifar T Shooshtari FS,et al. Association between biofilm formation,structure,and the expression levels of genes related to biofilm formation and Biofilm-specific resistance of Acinetobacter baumannii strains isolated from burn infection in Ahvaz,Iran[J]. Infect Drug Resist201912:3867-3881.
11
Kim DH Choi JY Kim HW,et al. Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands[J]. Antimicrob Agents Chemother201357(11):5239-5246.
12
Li J Hu WW Qu GX,et al. Characterization of a type VI secretion system vgrG2 gene in the pathogenicity of Burkholderia thailandensis BPM[J]. Front Microbiol202112:811343.
13
Mostafavi SKS Najar-Peerayeh S Mobarez AM,et al. Characterization of uropathogenic E.coli O25b-B2-ST131,O15:K52:H1,and CGA:Neutrophils apoptosis,serum bactericidal assay,biofilm formation,and virulence typing[J]. J Cell Physiol2019234(10):18272-18282.
14
Chen X Meng XB Gao QQ,et al. Meropenem selection induced overproduction of the intrinsic carbapenemase as well as phenotype divergence in Acinetobacter baumannii [J]. Int J Antimicrob Agents201750(3):419-426.
15
Mok WWK Orman MA Brynildsen MP. Impacts of global transcriptional regulators on persister metabolism[J]. Antimicrob Agents Chemother201559(5):2713-2719.
16
董俊芳,王 萍,刘存伟,等. 鲍曼不动杆菌无痕基因敲除及hcp基因相关功能[J]. 微生物学通报202148(3):811-819.
Dong JF Wang P Liu CW,et al. Marker-less gene deletion and the function of hcp gene in Acinetobacter baumannii [J]. Microbiol China202148(3):811-819.
17
Luo LM Wu LJ Xiao YL,et al. Enhancing pili assembly and biofilm formation in Acinetobacter baumannii ATCC19606 using non-native acyl-homoserine lactones[J]. BMC Microbiol201515:62.
18
Saipriya K Swathi CH Ratnakar KS,et al. Quorum-sensing system in Acinetobacter baumannii:a potential target for new drug development[J]. J Appl Microbiol2020128(1):15-27.
19
黄丽华, 刘 娇, 彭雪儿 等. 2019~2021年某肿瘤专科医院院内感染情况分析[J]. 中山大学学报(医学科学版)202344(4):697-703.
Huang LH Liu J Peng XE,et al. Analysis of nosocomial infection in a cancer hospital from 2019 to 2021[J]. J Sun Yat Sen Univ Med Sci202344(4):697-703.
20
李 雯,徐 丹, 成孟芹. 消化内科老年患者医院感染病原菌分布、危险因素分析及对策研究[J]. 重庆医科大学学报202348(4):467-471.
Li W Xu D Cheng MQ. Analysis of pathogenic bacteria distribution,risk factors and countermeasures of nosocomial infection in elderly patients in gastroenterology department[J]. J Chongqing Med Univ202348(4):467-471.
21
窦 懿. 鲍曼不动杆菌群体感应系统信号分子N-酰基高丝氨酸内酯的鉴定以及与耐药基因相关性的研究[D]. 上海: 上海交通大学,  2015.
Dou Y. Identification of N- acyl homoserine lactone,a signal molecule of quorum sensing system of Acinetobacter baumannii,and its correlation with drug resistance genes[D]. Shanghai:Shanghai Jiao Tong University,2015.
22
Tang J Chen Y Wang XL,et al. Contribution of the AbaI/AbaR quorum sensing system to resistance and virulence of Acinetobacter baumannii clinical strains[J]. Infect Drug Resist202013:4273-4281.
23
Choi SJ Kim ES. Optimizing treatment for carbapenem-resistant Acinetobacter baumannii complex infections:a review of current evidence[J]. Infect Chemother202456(2):171-187.

基金

重庆市自然科学基金面上资助项目(cstc2020jcyj-msxmX0207)

评论

PDF(1593 KB)

Accesses

Citation

Detail

段落导航
相关文章

/