β-lactam Antibiotics Stimulate the Pathogenicity of Methicillin-resistant <i>Staphylococcus aureus</i> Via SarA-controlled Tandem Lipoprotein Expression

Shang, Wenjun; Rao, Yifan; Yang, Yi; Hu, Qiwen; Hu, Zhen; Yuan, Jizhen; Peng, Huagang; Xiong, Kun; Tan, Li; Li, Shu; Zhu, Jing; Li, Ming; Hu, Xiaomei; Mao, Xuhu; Rao, Xiancai

doi:10.1101/353227

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“…The IL-10 cytokine family has been shown to facilitate the gut antimicrobial defense and promote mucosal barrier integrity and repair by activating STAT3 ( Shouval et al, 2014 ), while IL-17, TNF-α, and IFN-γ induce colitis by disrupting the mucosal barrier function of the immune system ( Leppkes et al, 2009 ; Friedrich et al, 2019 ). Studies have shown that the β-lactam antibiotic oxacillin stimulates the expression of lipoprotein-like (lpl) genes in methicillin-resistant Staphylococcus aureus (MRSA), which promotes the production of the proinflammation cytokines IL-6 and TNF-α in macrophages to trigger a TLR2-dependent immune response in mice ( Shang et al, 2018 ). In agreement with these results, we showed that AMO treatment-associated changes in K. variicola also induce the production of proinflammatory cytokines such as cytokine IL-17a, TNF-α, and IFN-γ.…”

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confidence: 99%

Colonization of Mice With Amoxicillin-Associated Klebsiella variicola Drives Inflammation via Th1 Induction and Treg Inhibition

et al. 2020

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β-Lactam antibiotics can increase the resistance and virulence of individual intestinal microorganisms, which may affect host physiology and health. Klebsiella, a crucial gut inhabitant, has been confirmed to be resistant to most β-lactam antibiotics and contributes to the etiology of inflammatory bowel disease (IBD). In this study, the influence of amoxicillin (AMO) on Klebsiella and its role in colitis was investigated in an antibiotic cocktail (ABx) murine model. The results suggested that a 7-day AMO treatment significantly enriched the abundance of Klebsiella and enhanced serum resistance, antibiotic resistance, and biofilm formation ability of Klebsiella variicola (K. variicola) compared to the wild-type strain in the control group mice. Colonization of mice with the AMO-associated K. variicola could induce Th1 cells and inhibit Treg differentiation to promote inflammation in ABx murine model. In addition, inoculation of AMO-associated K. variicola in dextran sodium sulfate (DSS)-induced colitis murine model mice also confirmed that K. variicola colonization exacerbated inflammation as assessed by increased TNF-α, IFN-γ, IL-17a, and disease activity (DAI) levels; decreased colon length and bodyweight; and a disrupted Th1/Treg balance. The results of our study demonstrate that AMO enhances Klebsiella virulence in mice by disrupting the T cell equilibrium to exacerbate colitis, thereby providing a reference for proper antibiotic prescription.

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