Academic Journal
Lipopolysaccharide-Deficient Acinetobacter baumannii Due to Colistin Resistance Is Killed by Neutrophil-Produced Lysozyme
| العنوان: | Lipopolysaccharide-Deficient Acinetobacter baumannii Due to Colistin Resistance Is Killed by Neutrophil-Produced Lysozyme |
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| المؤلفون: | Go Kamoshida, Takuya Akaji, Norihiko Takemoto, Yusuke Suzuki, Yoshinori Sato, Daichi Kai, Taishi Hibino, Daiki Yamaguchi, Takane Kikuchi-Ueda, Satoshi Nishida, Yuka Unno, Shigeru Tansho-Nagakawa, Tsuneyuki Ubagai, Tohru Miyoshi-Akiyama, Masataka Oda, Yasuo Ono |
| المصدر: | Frontiers in Microbiology, Vol 11 (2020) |
| بيانات النشر: | Frontiers Media S.A., 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Microbiology |
| مصطلحات موضوعية: | Acinetobacter baumannii, colistin, LPS, lysozyme, neutrophil, Microbiology, QR1-502 |
| الوصف: | Acinetobacter baumannii causes nosocomial infections due to its multidrug resistance and high environmental adaptability. Colistin is a polypeptide antibacterial agent that targets lipopolysaccharide (LPS) and is currently used to control serious multidrug-resistant Gram-negative bacterial infections, including those caused by A. baumannii. However, A. baumannii may acquire colistin resistance by losing their LPS. In mouse models, LPS-deficient A. baumannii have attenuated virulence. Nevertheless, the mechanism through which the pathogen is cleared by host immune cells is unknown. Here, we established colistin-resistant A. baumannii strains and analyzed possible mechanisms through which they are cleared by neutrophils. Colistin-resistant, LPS-deficient strains harbor mutations or insertion sequence (IS) in lpx genes, and introduction of intact lpx genes restored LPS deficiency. Analysis of interactions between these strains and neutrophils revealed that compared with wild type, LPS-deficient A. baumannii only weakly stimulated neutrophils, with consequent reduced levels of reactive oxygen species (ROS) and inflammatory cytokine production. Nonetheless, neutrophils preferentially killed LPS-deficient A. baumannii compared to wild-type strains. Moreover, LPS-deficient A. baumannii strains presented with increased sensitivities to antibacterial lysozyme and lactoferrin. We revealed that neutrophil-secreted lysozyme was the antimicrobial factor during clearance of LPS-deficient A. baumannii strains. These findings may inform the development of targeted therapeutics aimed to treat multidrug-resistant infections in immunocompromised patients who are unable to mount an appropriate cell-mediated immune response. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1664-302X 42799309 |
| Relation: | https://www.frontiersin.org/article/10.3389/fmicb.2020.00573/full; https://doaj.org/toc/1664-302X |
| DOI: | 10.3389/fmicb.2020.00573 |
| URL الوصول: | https://doaj.org/article/e3310e94d20f427993094c95b0fcdbbf |
| رقم الانضمام: | edsdoj.3310e94d20f427993094c95b0fcdbbf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 1664302X 42799309 |
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| DOI: | 10.3389/fmicb.2020.00573 |