Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is highly prevalent and poses a significant threat to public health. In critically ill patients, gut colonization is considered to be the reservoir of recurrent CRKP infection. Therefore, eliminating CRKP carriage in the intestine is critical for preventing subsequent CRKP infection. In the present study, Lactobacillus plantarum LP1812, a probiotic that can inhibit CRKP in vitro, was used as a candidate probiotic to investigate its efficacy for CRKP anticolonization. Compared with the control, mice fed with 1×10 8 CFU L. plantarum LP1812 exhibited significant CRKP clearance from 1×10 4 CFU/mg to less than 10 CFU/mg in mice feces. Furthermore, 16S RNA gene sequencing revealed that L. plantarum LP1812 modulated mice microbiota by increasing the relative abundance of the genus Halomanas, Blautia, and Holdemania. Further KEGG pathway enrichment analysis revealed that fatty acid-utilizing bacteria, such as acetate-producing Bacteroidetes and Blautia flourished in mice fed with L. plantarum LP1812. Moreover, we found that the concentration of acetic acid was higher in L. plantarum LP1812, which inhibited the growth of K. pneumoniae strains in vitro. Meanwhile, mice intragastrically administered with acetic acid exhibited significantly increased CRKP elimination in vivo. In conclusion, L. plantarum LP1812 is a potential candidate for intestinal CRKP anticolonization by regulating the intestinal microbiota and inhibiting CRKP via increased acetic acid in the intestinal lumen.

Highlights

  • Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common nosocomial pathogen that causes infection in a variety of locations, including the lower respiratory tract, urinary tract, and the bloodstream (Pendleton et al, 2013), posing a significant threat to public health (Michalopoulos et al, 2011; Musicha et al, 2017)

  • L. plantarum LP1812 was able to eradicate K. pneumoniae strains in 8 hours

  • CRKP belongs to Enterobacterales, is regarded as a main nosocomial pathogen that can cause severe infection in critically ill patients (Medrzycka-Dabrowska et al, 2021), and its intestinal colonization is a risk factor for recurrent bloodstream infection (Kontopoulou et al, 2019)

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Summary

Introduction

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common nosocomial pathogen that causes infection in a variety of locations, including the lower respiratory tract, urinary tract, and the bloodstream (Pendleton et al, 2013), posing a significant threat to public health (Michalopoulos et al, 2011; Musicha et al, 2017). Numerous decolonization studies have been undertaken, including selective digestive decontamination with colistin or aminoglycosides (Machuca et al, 2016; Stoma et al, 2018), custom-made bacteriophage (Hua et al, 2017; Corbellino et al, 2020; Liu et al, 2021) and fecal microbiota transplantation (FMT) (Alagna et al, 2020; Gouveia et al, 2020; Ueckermann, et al, 2020) Those methods demonstrated some decolonization effects, the possibility of drug resistance induced by gentamycin or colistin, the high cost and prolonged waiting time for phage, and the possibility of infectious agent transmission accompanied by FMT rendered them impractical for generalization. Probiotics are promising candidates for eradicating CRKP in the intestine with fewer adverse effects and expenses

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