Klebsiella pneumoniae
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            Fucose Metabolism Promotes Gastrointestinal Colonization and Modulates Its Virulence Determinants

Hudson, Andrew W; Barnes, Andrew J.; Bray, Andrew S.; Ornelles, David A.; Zafar, M. Ammar

doi:10.1128/iai.00206-22

Cited by 36 publications

(27 citation statements)

References 84 publications

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“…Hudson and colleagues demonstrated that K. pneumoniae was also able to utilize mucin-derived fucose to support its growth in the mouse intestine [88]. They found that a K.…”

Section: Introductionmentioning

confidence: 99%

Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization

et al. 2023

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The human gut microbiota can restrict the growth of pathogens to prevent them from colonizing the intestine (‘colonization resistance’). However, antibiotic treatment can kill members of the gut microbiota (‘gut commensals’) and reduce competition for nutrients, making these nutrients available to support the growth of pathogens. This disturbance can lead to the growth and expansion of pathogens within the intestine (including antibiotic-resistant pathogens), where these pathogens can exploit the absence of competitors and the nutrient-enriched gut environment. In this review, we discuss nutrient competition between the gut microbiota and pathogens. We also provide an overview of how nutrient competition can be harnessed to support the design of next-generation microbiome therapeutics to restrict the growth of pathogens and prevent the development of invasive infections.

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“…Hudson and colleagues demonstrated that K. pneumoniae was also able to utilize mucin-derived fucose to support its growth in the mouse intestine [88]. They found that a K.…”

Section: Introductionmentioning

confidence: 99%

Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization

et al. 2023

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“…Nevertheless, the importance of ecological diversity and complexity is observed for both pathogens. We anticipate that the importance of ecological diversity and the principle of nutrient blocking will apply generally, given the widespread evidence that nutrient competition is important for diverse species in the microbiome, including many other pathogens (9,(47)(48)(49)(50)(51)(52)(53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

Microbiome diversity protects against pathogens by nutrient blocking

Spragge,

Bakkeren,

Jahn

et al. 2023

Science

105

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The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonization of two major bacterial pathogens, both in vitro and in gnotobiotic mice. Whereas single species alone had negligible effects, colonization resistance greatly increased with community diversity. Moreover, this community-level resistance rested critically upon certain species being present. We explained these ecological patterns through the collective ability of resistant communities to consume nutrients that overlap with those used by the pathogen. Furthermore, we applied our findings to successfully predict communities that resist a novel target strain. Our work provides a reason why microbiome diversity is beneficial and suggests a route for the rational design of pathogen-resistant communities.

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“…Consequently, the World Health Organization has designated development of novel anti-Klebsiella control strategies an urgent global priority [2]. Many existing antimicrobials target or alter cellular metabolic processes, and recent works have highlighted a role for metabolism in K. pneumoniae virulence [3,4], supporting these processes as prime targets for novel therapeutics. For example, production of the GltA citrate synthase appears to facilitate liver and spleen infections in mouse models [5], while a psicose sugar utilization locus has been associated with lung infection [6].…”

Section: Introductionmentioning

confidence: 99%

A validated pangenome-scale metabolic model for the Klebsiella pneumoniae species complex

Cooper,

Vezina,

Hawkey

et al. 2024

Microbial Genomics

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The Klebsiella pneumoniae species complex (KpSC) is a major source of nosocomial infections globally with high rates of resistance to antimicrobials. Consequently, there is growing interest in understanding virulence factors and their association with cellular metabolic processes for developing novel anti-KpSC therapeutics. Phenotypic assays have revealed metabolic diversity within the KpSC, but metabolism research has been neglected due to experiments being difficult and cost-intensive. Genome-scale metabolic models (GSMMs) represent a rapid and scalable in silico approach for exploring metabolic diversity, which compile genomic and biochemical data to reconstruct the metabolic network of an organism. Here we use a diverse collection of 507 KpSC isolates, including representatives of globally distributed clinically relevant lineages, to construct the most comprehensive KpSC pan-metabolic model to date, KpSC pan v2. Candidate metabolic reactions were identified using gene orthology to known metabolic genes, prior to manual curation via extensive literature and database searches. The final model comprised a total of 3550 reactions, 2403 genes and can simulate growth on 360 unique substrates. We used KpSC pan v2 as a reference to derive strain-specific GSMMs for all 507 KpSC isolates, and compared these to GSMMs generated using a prior KpSC pan-reference (KpSC pan v1) and two single-strain references. We show that KpSC pan v2 includes a greater proportion of accessory reactions (8.8 %) than KpSC pan v1 (2.5 %). GSMMs derived from KpSC pan v2 also generate more accurate growth predictions, with high median accuracies of 95.4 % (aerobic, n=37 isolates) and 78.8 % (anaerobic, n=36 isolates) for 124 matched carbon substrates. KpSC pan v2 is freely available at https://github.com/kelwyres/KpSC-pan-metabolic-model, representing a valuable resource for the scientific community, both as a source of curated metabolic information and as a reference to derive accurate strain-specific GSMMs. The latter can be used to investigate the relationship between KpSC metabolism and traits of interest, such as reservoirs, epidemiology, drug resistance or virulence, and ultimately to inform novel KpSC control strategies.

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Klebsiella pneumoniae l- Fucose Metabolism Promotes Gastrointestinal Colonization and Modulates Its Virulence Determinants

Cited by 36 publications

References 84 publications

Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization

Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization

Microbiome diversity protects against pathogens by nutrient blocking

A validated pangenome-scale metabolic model for the Klebsiella pneumoniae species complex

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