Anticolonization of Carbapenem-Resistant Klebsiella pneumoniae by Lactobacillus plantarum LP1812 Through Accumulated Acetic Acid in Mice Intestinal

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.

Clinical use of tigecycline may contribute to the widespread dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae strains

“…Recent studies have reported that the anticolonization of K. pneumoniae by Lactobacillus spp. was attributed to increased acetic acid and regulation in microbiota in mice intestinal [ 29 , 34 ]. To investigate the mechanism underlying the inhibition of CR-hvKP colonization by Lactobacillus spp., we repeated the K. pneumoniae colonization experiment and replaced Lactobacillus spp.…”

“…The co-culture assay was performed as previously described [ 29 ]. K. pneumoniae and Lactobacillus spp.…”

Active learning for medium optimization for selective bacterial culture

“…4). Although Lp producing acetic acid might inhibit Ec 29, 30, 31 , the media developed for Ec growth (M1-3_Ec) remained specificity in the presence of Lp . The results suggested that the ML-assisted medium optimization and specialization were practical, and the resultant media were robust regardless of mono- or co-culture.…”

Oral Administration of Lacticaseibacillus rhamnosus CRL1505 Modulates Lung Innate Immune Response against Klebsiella pneumoniae ST25

“…Using in vitro approaches or mice models of multiresistant K. pneumoniae intestinal colonization, it was demonstrated that some Lactobacillus spp. strains diminished the pathogen colonization and biofilm formation [ 8 , 9 , 10 , 11 , 12 ]. The ability of lactobacilli to inhibit the colonization of K. pneumoniae was associated with organic acid production [ 10 , 11 ] and the secretion of proteins with antimicrobial activity [ 13 , 14 ].…”

“…strains diminished the pathogen colonization and biofilm formation [ 8 , 9 , 10 , 11 , 12 ]. The ability of lactobacilli to inhibit the colonization of K. pneumoniae was associated with organic acid production [ 10 , 11 ] and the secretion of proteins with antimicrobial activity [ 13 , 14 ]. In addition, few studies reported that the oral administration of probiotic microorganisms to mice significantly reduced the lung inflammatory damage induced by K. pneumoniae nasal challenge [ 15 , 16 ], demonstrating that immunomodulatory bacteria are an interesting alternative to enhance resistance to this pathogen.…”