Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition

Osbelt, Lisa; Wende, Marie; Almási, Éva; Derksen, Elisabeth; Muthukumarasamy, Uthayakumar; Lesker, Till Robin; Galvez, Eric; Pils, Marina C.; Schalk, Enrico; Chhatwal, Patrick; Färber, Jacqueline; Neumann‐Schaal, Meina; Fischer, Thomas; Schlüter, Dirk; Strowig, Till

doi:10.1016/j.chom.2021.09.003

Cited by 84 publications

(94 citation statements)

References 62 publications

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“…This result was consistent with a recent study that two strains belonging to the family Enterobacteriaceae strongly compete for carbohydrate, even leading to colonization resistance. 30 Thus, the enrichment of the abundance of Enterobacteriaceae with worsening NAFLD severity observed in the HC group might be attributed to ample opportunities for carbohydrate utilization.…”

Section: Discussionmentioning

confidence: 97%

Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis

et al. 2022

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Nonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). Stool samples were collected from 204 Korean subjects with biopsy-proven NAFLD (n = 129) and without NAFLD (n = 75). The gut microbiome profiles were analyzed using 16S rRNA amplicon sequencing. Study subjects were grouped by the NAFLD activity score (NAS) and percentage energy intake from dietary carbohydrate. Hepatic DNL-related transcripts were also analyzed (n = 90). Data from the Korean healthy twin cohort (n = 682), a large sample of individuals without NAFLD, were used for comparison and validation. A HC diet rather than a low carbohydrate diet was associated with the altered gut microbiome diversity according to the NAS. Unlike individuals from the twin cohort without NAFLD, the abundances of Enterobacteriaceae and Ruminococcaceae were significantly different among the NAS subgroups in NAFLD subjects who consumed an HC diet. The addition of these two microbial families, along with Veillonellaceae , significantly improved the diagnostic performance of the predictive model, which was based on the body mass index, age, and sex to predict nonalcoholic steatohepatitis in the HC group. In the HC group, two crucial regulators of DNL ( SIRT1 and SREBF2 ) were differentially expressed among the NAS subgroups. In particular, kernel causality analysis revealed a causal effect of the abundance of Enterobacteriaceae on SREBF2 upregulation and of the surrogate markers of insulin resistance on NAFLD activity in the HC group. Consuming an HC diet is associated with alteration in the gut microbiome, impaired glucose homeostasis, and upregulation of hepatic DNL genes, altogether contributing to NAFLD pathogenesis.

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Section: Discussionmentioning

confidence: 97%

Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis

et al. 2022

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“…Interestingly, fecal tryptophan levels were reported to be decreased in preterm infants exposed to early antibiotics ( 64 ), and several studies suggest that antibiotic use in preterm infants increases the risk of NEC ( 65 , 66 ). Members of the K. oxytoca complex also utilize a broader array of sugars than other Klebsiella spp., which may provide the fermentative energy to support toxin production and promote colonization resistance of other enteric bacteria ( 67 , 68 ). Perturbations in the gut microbiome leading to excessive Toll-like receptor 4 (TLR4) stimulation have been suggested as an inciting event in NEC pathogenesis ( 69 , 70 ), whereas others have challenged the notion that NEC represents a single disease entity ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

Bacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity

Ledala

Malik

Rezaul

et al. 2022

mBio

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“…In addition, our growth results in CF suggest a potential role for probiotics in preventing K. pneumoniae colonization. Recently, K. oxytoca was demonstrated to provide CR against a K. pneumoniae MDR isolate (15). EcN has previously been shown to protect the murine GI tract from EHEC colonization (3, 61), and at 24 hours post-inoculation likewise out-competed both the WT and ΔfucI strains when grown in vitro .…”

Section: Discussionmentioning

confidence: 99%

“…Despite the clinical importance of K. pneumoniae , how it colonizes the gut is poorly understood (10). Although a few recent studies have focused on gut commensals that provide CR against K. pneumoniae (15, 16). Metabolic flexibility is critical for bypassing nutritional limitations in the GI tract to overcome CR.…”

Section: Introductionmentioning

confidence: 99%

Klebsiella pneumoniae L-Fucose metabolism promotes gastrointestinal colonization and modulates its virulence determinants

Hudson

Barnes

Bray

et al. 2022

Preprint

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Colonization of the gastrointestinal (GI) tract by Klebsiella pneumoniae (K. pneumoniae) is generally considered asymptomatic. However, gut colonization allows K. pneumoniae to either translocate to sterile site within the same host or transmit through the fecal-oral route to another host. K. pneumoniae gut colonization is poorly understood, but knowledge of this first step toward infection and spread is critical for combatting its disease manifestations. K. pneumoniae must overcome colonization resistance (CR) provided by the host microbiota to establish itself within the gut. One such mechanism of CR is through nutrient competition. Pathogens that metabolizes a broad range of substrates have the ability to bypass nutrient competition and overcome CR. Herein, we demonstrate that in response to mucin derived fucose, the conserved fucose metabolism operon (fuc) of K. pneumoniae is upregulated in the murine gut and subsequently show that fucose metabolism promotes robust gut colonization. Growth studies using cecal filtrate as a proxy for the gut lumen illustrates the growth advantage that the fuc operon provides K. pneumoniae. We further show that fucose metabolism allows K. pneumoniae to be competitive with a commensal E. coli isolate (Nissle). However, Nissle is eventually able to out-compete K. pneumoniae, suggesting that it can be utilized to enhance CR. Lastly, we observed that fucose metabolism positively modulates hypermucoviscosity, auto-aggregation, and biofilm formation, but not capsule biogenesis. Together, these insights enhance our understanding of the role of alternative carbon sources on K. pneumoniae gut colonization and the complex relationship between metabolism and virulence in this species.

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Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition

Cited by 84 publications

References 62 publications

Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis

Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis

Bacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity

Klebsiella pneumoniae L-Fucose metabolism promotes gastrointestinal colonization and modulates its virulence determinants

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