Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii
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 treat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01379/full |
| _version_ | 1819183050380017664 |
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| author | Weiwei Huang Qishu Zhang Weiran Li Yongjun Chen Congyan Shu Qingrong Li Jingxian Zhou Chao Ye Hongmei Bai Wenjia Sun Xu Yang Yanbing Ma |
| author_facet | Weiwei Huang Qishu Zhang Weiran Li Yongjun Chen Congyan Shu Qingrong Li Jingxian Zhou Chao Ye Hongmei Bai Wenjia Sun Xu Yang Yanbing Ma |
| author_sort | Weiwei Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T22:55:51Z |
| format | Article |
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| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T22:55:51Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-63ad128266f84ae2ab9d14b2f82bb6022022-12-21T18:09:49ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-06-011010.3389/fmicb.2019.01379463576Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumanniiWeiwei Huang0Qishu Zhang1Weiran Li2Yongjun Chen3Congyan Shu4Qingrong Li5Jingxian Zhou6Chao Ye7Hongmei Bai8Wenjia Sun9Xu Yang10Yanbing Ma11Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaSichuan Institute for Food and Drug Control, Chengdu, ChinaThe Second Affiliated Hospital of Kunming Medical University, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaAcinetobacter 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.https://www.frontiersin.org/article/10.3389/fmicb.2019.01379/fullantibiotic resistanceAcinetobacter baumanniiantibodiesouter membrane vesiclesouter membrane proteins |
| spellingShingle | Weiwei Huang Qishu Zhang Weiran Li Yongjun Chen Congyan Shu Qingrong Li Jingxian Zhou Chao Ye Hongmei Bai Wenjia Sun Xu Yang Yanbing Ma Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii Frontiers in Microbiology antibiotic resistance Acinetobacter baumannii antibodies outer membrane vesicles outer membrane proteins |
| title | Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii |
| title_full | Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii |
| title_fullStr | Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii |
| title_full_unstemmed | Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii |
| title_short | Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant Acinetobacter baumannii |
| title_sort | anti outer membrane vesicle antibodies increase antibiotic sensitivity of pan drug resistant acinetobacter baumannii |
| topic | antibiotic resistance Acinetobacter baumannii antibodies outer membrane vesicles outer membrane proteins |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01379/full |
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