دورية أكاديمية
أعرض في EDS

Fingolimod synergizes and reverses K. pneumoniae resistance to colistin.

التفاصيل البيبلوغرافية
العنوان: Fingolimod synergizes and reverses K. pneumoniae resistance to colistin.
المؤلفون: Geng X; Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China., Zhang ZD; Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China., Li YX; Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China., Hao RC; Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China., Yang YJ; Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China., Liu XW; Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China., Li JY; Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China.
المصدر: Frontiers in microbiology [Front Microbiol] 2024 May 30; Vol. 15, pp. 1396663. Date of Electronic Publication: 2024 May 30 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101548977 Publication Model: eCollection Cited Medium: Print ISSN: 1664-302X (Print) Linking ISSN: 1664302X NLM ISO Abbreviation: Front Microbiol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: Klebsiella pneumoniae ( K. pneumoniae ) infection and the rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. Polymyxin E (colistin), a group of cationic antimicrobial polypeptides, is currently one of the last resort treatment options against carbapenem-resistant Gram-negative pathogens. The effectiveness of colistin has been compromised due to its intensive use. This study found that fingolimod (FLD), a natural product derivative, exhibited a significant synergistic bactericidal effect on K. pneumoniae when combined with colistin, both in vitro and in vivo . The checkerboard method was employed to assess the in vitro synergistic effect of FLD with colistin. FLD enhanced the susceptibility of bacteria to colistin and lowered effectively minimum inhibitory concentrations (MIC) when compared to colistin MIC, and the fractional inhibitory concentrations (FIC) value was less than 0.3. The time-kill curve demonstrated that the combination treatment of FLD and colistin had significant bactericidal efficacy. The in vitro concurrent administration of colistin and FLD resulted in heightening membrane permeability, compromising cell integrity, diminishing membrane fluidity, and perturbing membrane homeostasis. They also induced alterations in membrane potential, levels of reactive oxygen species, and adenosine triphosphate synthesis, ultimately culminating in bacterial death. Moreover, the combination of FLD with colistin significantly influenced fatty acid metabolism. In the mouse infection model, the survival rate of mice injected with K. pneumoniae was significantly improved to 67% and pathological damage was significantly relieved with combination treatment of FLD and colistin when compared with colistin treatment. This study highlights the potential of FLD in combining with colistin for treating infections caused by MDR isolates of K. pneumoniae .
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Geng, Zhang, Li, Hao, Yang, Liu and Li.)
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فهرسة مساهمة: Keywords: K. pneumoniae; antibiotic; colistin; fingolimod (FLD); synergistic
تواريخ الأحداث: Date Created: 20240614 Latest Revision: 20240615
رمز التحديث: 20240615
مُعرف محوري في PubMed: PMC11169662
DOI: 10.3389/fmicb.2024.1396663
PMID: 38873155
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-302X
DOI:10.3389/fmicb.2024.1396663