Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii

被引:37
|
作者
Huang, Weiwei [1 ,2 ]
Zhang, Qishu [1 ,2 ]
Li, Weiran [1 ,2 ]
Chen, Yongjun [1 ,2 ]
Shu, Congyan [3 ]
Li, Qingrong [4 ]
Zhou, Jingxian [1 ,2 ]
Ye, Chao [1 ,2 ]
Bai, Hongmei [1 ,2 ]
Sun, Wenjia [1 ,2 ]
Yang, Xu [1 ,2 ]
Ma, Yanbing [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Lab Mol Immunol, Inst Med Biol, Kunming, Yunnan, Peoples R China
[2] Peking Union Med Coll, Kunming, Yunnan, Peoples R China
[3] Sichuan Inst Food & Drug Control, Chengdu, Sichuan, Peoples R China
[4] Kunming Med Univ, Affiliated Hosp 2, Kunming, Yunnan, Peoples R China
基金
中国国家自然科学基金;
关键词
antibiotic resistance; Acinetobacter baumannii; antibodies; outer membrane vesicles; outer membrane proteins; ELICITS PROTECTIVE IMMUNITY; AMINOGLYCOSIDE RESISTANCE; PSEUDOMONAS-AERUGINOSA; MONOCLONAL-ANTIBODIES; MULTIDRUG-RESISTANCE; EFFLUX PUMP; PROTEIN; OMPA; IDENTIFICATION; IMMUNIZATION;
D O I
10.3389/fmicb.2019.01379
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Acinetobacter baumannii often causes serious nosocomial infections. Because of its serious drug resistance problems, complex drug resistance mechanism, and rapid adaptation to antibiotics, it often shows pan-drug resistance and high fatality rates, which represent great challenges for clinical treatment. Therefore, identifying new ways to overcome antibiotic resistance is particularly important. In this study, mice immunized with A. baumannii outer membrane vesicles (AbOMVs) produced high IgG levels for a long time, and this antiserum significantly increased the small molecule intracellular aggregation rate and concentrations. In vitro experiments demonstrated that the combined used of anti-AbOMV serum and quinolone antibiotics significantly increased the sensitivity of the bacteria to these antibiotics. Mouse sepsis model experiments demonstrated that delivery of these antibodies using both active and passive immunization strategies significantly improved the susceptibility to quinolone antibiotics, improved the survival rate of mice infected with A. baumannii, and reduced the bacterial load in the organs. In a pneumonia model, the combination of serum anti-AbOMVs and levofloxacin improved levofloxacin sensitivity, which significantly reduced the bacterial loads in the lung and spleen compared with those of the antibiotic or antibody alone. This combination also significantly reduced lung inflammatory cell infiltration and inflammatory cytokine aggregation. In this study, the main protein targets that bound to these antibodies were identified. Structural modeling showed that seven of the proteins were porins. Therefore, we speculated that the anti-AbOMV antibodies mainly improved the intracellular aggregation of antibiotics by affecting porins, thus improving susceptibility to quinolone antibiotics. This study provides a method to improve susceptibility to existing antibiotics and a novel idea for the prevention and treatment of pan-drug-resistant A. baumannii.
引用
收藏
页数:16
相关论文
共 16 条
  • [1] Effects of specific egg yolk immunoglobulin on pan-drug-resistant Acinetobacter baumannii
    Shi, Huaying
    Zhu, Jie
    Zou, Boyang
    Shi, Lei
    Du, Linying
    Long, Yayi
    Wang, Huaxin
    Xu, Hong
    Zhen, Yuhong
    Sun, Lidan
    BIOMEDICINE & PHARMACOTHERAPY, 2017, 95 : 1734 - 1742
  • [2] Nosocomial Outbreak of Infection With Pan-Drug-Resistant Acinetobacter baumannii in a Tertiary Care University Hospital
    Valencia, Raquel
    Arroyo, Luis A.
    Conde, Manuel
    Aldana, Josefa M.
    Torres, Maria-Jose
    Fernandez-Cuenca, Felipe
    Garnacho-Montero, Jose
    Cisneros, Jose M.
    Ortiz, Carlos
    Pachon, Jeronimo
    Aznar, Javier
    INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY, 2009, 30 (03): : 257 - 263
  • [3] A bovine myeloid antimicrobial peptide (BMAP-28) and its analogs kill pan-drug-resistant Acinetobacter baumannii by interacting with outer membrane protein A (OmpA)
    Guo, Yijie
    Xun, Meng
    Han, Jing
    MEDICINE, 2018, 97 (42)
  • [4] In vitro antibacterial activity of combinations of fosfomycin, minocycline and polymyxin B on pan-drug-resistant Acinetobacter baumannii
    Zhang, Yajun
    Chen, Fengzhe
    Sun, Enhua
    Ma, Ruiping
    Qu, Chunmei
    Ma, Lixian
    EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2013, 5 (06) : 1737 - 1739
  • [5] Seroprevalence of bactericidal and anti-outer membrane vesicle antibodies to Neisseria meningitildis group B in England
    Trotter, Caroline
    Findlow, Jamie
    Balmer, Paul
    Holland, Ann
    Barchha, Rita
    Hamer, Nick
    Andrews, Nick
    Miller, Elizabeth
    Borrow, Ray
    CLINICAL AND VACCINE IMMUNOLOGY, 2007, 14 (07) : 863 - 868
  • [6] Meropenem in combination with baicalein exhibits synergism against extensively drug resistant and pan-drug-resistant Acinetobacter baumannii clinical isolates in vitro
    Guran, Mumtaz
    Cakiral, Kadir
    Terali, Kerem
    Kandemir, Tulay
    Sanliturk, Gizem
    Ocal, Melda Meral
    Nagiyev, Togrul
    Koksal, Fatih
    PATHOGENS AND DISEASE, 2023, 81
  • [7] Synergy Testing by Etest, Microdilution Checkerboard, and Time-Kill Methods for Pan-Drug-Resistant Acinetobacter baumannii
    Sopirala, Madhuri M.
    Mangino, Julie E.
    Gebreyes, Wondwossen A.
    Biller, Beth
    Bannerman, Tammy
    Balada-Llasat, Joan-Miquel
    Pancholi, Preeti
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (11) : 4678 - 4683
  • [8] In Vivo Selection of Pan-Drug Resistant Acinetobacter baumannii during Antibiotic Treatment
    Kim, Yoonjung
    Bae, Il Kwon
    Jeong, Seok Hoon
    Yong, Dongeun
    Lee, Kyungwon
    YONSEI MEDICAL JOURNAL, 2015, 56 (04) : 928 - 934
  • [9] Antimicrobial and Antibiofilm Activity of Human Cationic Antibacterial Peptide (LL-37) and Its Analogs Against Pan-Drug-Resistant Acinetobacter baumannii
    Guo, Yijie
    Wang, Ling
    Lei, Jine
    Xu, Jiru
    Han, Lei
    JUNDISHAPUR JOURNAL OF MICROBIOLOGY, 2017, 10 (03)
  • [10] Combined Strategy for Post-Operative Patients with Central Nervous System Infections Caused by Extensively Drug-Resistant/Pan-Drug-Resistant Acinetobacter baumannii: A Retrospective Study
    Chang, Jian-bo
    Chen, Yihao
    Wang, He
    Ma, Xiaojun
    Zhang, Xiao
    Wu, Hao
    Ma, Baitao
    Zuo, Wei
    Ma, Wenbin
    Wang, Renzhi
    Wei, Junji
    SURGICAL INFECTIONS, 2020, 21 (10) : 853 - 858