Efficacy of lyophilized Lactobacillus sakei as a potential candidate for preventing carbapenem-resistant Klebsiella infection

Abstract

Background: Antimicrobial resistance is considered one of the greatest threats to human health, according to the World Health Organization (WHO). Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE), have become a significant concern in antimicrobial-resistant bacteria’s global emergence and spread. Among CRE pathogens, carbapenem-resistant Klebsiella pneumoniae (CRKP) has recently been reported as a highly infectious strain associated with high mortality and morbidity in adults and immunocompromised patients. Additionally, CRKP-related infections are challenging to treat, as carbapenems are the last resort of antibiotics. Therefore, developing novel drugs with different mechanisms of action from existing drugs is urgently required to defeat this lethal menace. Under such circumstances, probiotics can be therapeutic candidates for inhibiting pathogens. Thus, our research team has been focusing on probiotics for a long time to develop potential anti-CRKP drug agents. Methods: After extensive efforts, we finally found a novel probiotic strain, Lactobacillus sakei PMC104, suitable for treating CRKP infection. It was isolated from kimchi. As part of our expansion into therapeutic development, we evaluated the L. sakei strain effect against CRKP pathogens in both in vitro and in vivo experiments. Moreover, we conducted media optimization at food grade and then established a scale-up process on a pilot scale. Subsequently, a lyophilizate was obtained and used in a mouse model infected with CRKP. Results: Data demonstrated that the L. sakei strain has an inhibitory effect against CRKP infection both in in vitro and in vivo experiments and also increases the level of short-chain fatty acids in the feces of mice after receiving L. sakei strain treatment for 10 days. Furthermore, treatment with L. sakei powder remarkably diminished body weight loss, mortality, and illness severity in CRKP-infected mice, showing a preventive effect of our PMC 104 against CRKP infection. Discussion: Our results demonstrate the potential therapeutic effect of our candidate probiotic strain against CRKP, suggesting that L. sakei PMC 104 could be considered an antimicrobial candidate for treating CRKP infections. However, extensive studies, including additional toxicity tests and clinical trials, are still essential to develop it as a new anti-CRKP therapeutic agent.