Synergistic effect of chlorogenic acid and levofloxacin against Klebsiella pneumonia infection in vitro and in vivo

Author:

Tan Shirui,Gao Jing,Li Qingrong,Guo Tieying,Dong Xiangshu,Bai Xuehui,Yang Jinghui,Hao Shumei,He Feifei

Abstract

AbstractThe study aimed to investigate the antibacterial effect and potential mechanisms of chlorogenic acid (CA) in Klebsiella pneumonia (KPN) induced infection in vitro and in vivo. 62 KPN strains were collected from the First People’s Hospital of Yunnan Province. CA and CA combined Levofloxacin (LFX) were detected for KPN biofilm (BF) formation in vitro. The lung infection mice model were established by KPN. The effect of CA (500 mg/kg), LFX (50 mg/kg) and CA combined LFX (250 mg/kg + 25 mg/kg) were evaluated through the survival of mice, the changes of inflammation factors of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6 in serum, the histopathological analysis of lung and the protein expression of NLRP3 signaling pathway in vivo. A total of 62 KPNs were isolated and identified, of which 13 (21%) strains were BF positive. 8 (13%) strains were extended spectrum β-lactamase strains (ESBLs), and 20 (32%) strains are ESBLs biofilm positive. In vitro study, CA and LFX showed a synergistic effect on KPN biofilm formation. In vivo mice experiment, CA, especially CA + LFX treated group significantly decreased the serum levels of TNF-α, IL-1β and IL-6, improved the survival ratio and lung pathology changes, and also reduced the protein expression of ASC, caspase 1 p20, IL-1β and phosphor NF-κB p65. CA could effectively alleviate lung infection of KPN infected mice, and the antibacterial effection is strengthened by combined with LFX. The study provide a theroy basis for making rational and scientific antibacterial therapy strategy in clinic.

Funder

Key projects of the Ministry of Education of the People’s Republic of China with Yunnan University, Applied Basic Research Project of Yunnan

Major science and technology projects of Yunnan Province

The National Natural Science Foundation of Yunnan

The Scientific Research Fund of Yunnan province of China, Kunming Medical University Joint Research Project

The Fund of Yunnan Provincial Health Science and Technology Plan

Yunnan health training project of high level talents

Yunnan Provincial Key Laboratory of Clinical Virology

The National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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