Jingchun Kong,Yue Wang,Yijia Han,Huijing Zhou,Zhenyun Huang,Xiaodong Zhang,Cui Zhou,Tieli Zhou,Jianming Cao
Objectives The emergence of carbapenem-resistant Escherichia coli (CREC) is a global concern as its prevalence restricts treatment options and poses a considerable threat to public health. In this study, in vitro and in vivo activity of the antimicrobial peptide Octominin against CREC were evaluated, and investigated its possible mechanism of action was investigated. Furthermore, its safety and factors influencing its antibacterial effect were assessed. Additionally, the anti-inflammatory effects of Octominin were examined. Methods The antimicrobial activity of Octominin against 11 strains of CREC was determined using the broth microdilution method, growth curve, and time-kill assay. Its possible mechanism of action was unraveled using the propidium iodide and N-phenyl-1-naphthylamine fluorochrome and lipopolysaccharide-binding assays. To understand the safety and stability of Octominin, its cytotoxicity, hemolysis, and antibacterial activity under various conditions, such as temperature and ions, were estimated. Additionally, a Galleria mellonella infection model was utilized to evaluate the efficacy of Octominin in vivo , and qRT-PCR was performed to assess its impact on the expression of proinflammatory cytokines. Results Octominin displayed a significant antibacterial effect, with MICs of 4 to 8 μg/mL and MBCs of 8 to 16 μg/mL. Octominin exerted its antibacterial effect by disrupting bacterial membranes. Cytotoxicity and hemolysis tests demonstrated the potential application of Octominin in vivo . The G. mellonella infection model asserted the in vivo efficacy of Octominin. Furthermore, Octominin inhibited the expression of proinflammatory cytokines. Although the temperature had little effect on its the activity, serum and ions reduced activity. Conclusions Octominin is a promising alternative agent with remarkable antibacterial and anti-inflammatory effects for treating infections caused by CREC .
Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Escherichia coli (CREC) are frequently detected in clinical settings, restricting the use of carbapenems. Therefore, there is an urgent need for new antimicrobial strategies to address infections caused by CRKP and CREC. This study investigated the antibacterial, anti-biofilm, and anti-inflammatory effects of the cationic antimicrobial peptide Hs02, along with its potential antimicrobial mechanisms against CRKP and CREC. The results revealed that Hs02 had a low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against CRKP and CREC, effectively eliminating the bacteria within 30 min. Moreover, Hs02 significantly prevents biofilm formation and disrupts the established biofilms. Further mechanistic studies demonstrated that Hs02 specifically targeted and bound to bacterial outer membrane lipopolysaccharides (LPS), disrupted membrane permeability and integrity, which led to intracellular reactive oxygen species (ROS) accumulation. Furthermore, Hs02 neutralized LPS, thereby suppressing the production of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in murine macrophage RAW 264.7 cells. In vitro, hemolysis and cytotoxicity assays confirmed Hs02’s safety at the tested concentrations and proved that Hs02 improved the survival rate of Galleria mellonella larvae. In conclusion, the findings suggest that Hs02’s interaction with LPS and the resulting disruption of membrane integrity may be key factors driving its rapid bactericidal and anti-inflammatory effects.
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