What’s for dinner? How Citrobacter rodentium’s metabolism helps it thrive in the competitive gut

Liang, Q

doi:10.1016/j.mib.2021.06.004

Cited by 13 publications

(10 citation statements)

References 48 publications

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“…The intersection of metabolism and virulence in microbial pathogens is gaining attention in the quest to define the molecular mechanisms responsible for causing disease [ 33 ]. In particular, bacterial glycerol metabolism and the associated physiological landscape can influence disease pathogenesis [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick

et al. 2022

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We have identified GpsA, a predicted glycerol-3-phosphate dehydrogenase, as a virulence factor in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi: GpsA is essential for murine infection and crucial for persistence of the spirochete in the tick. B. burgdorferi has a limited biosynthetic and metabolic capacity; the linchpin connecting central carbohydrate and lipid metabolism is at the interconversion of glycerol-3-phosphate and dihydroxyacetone phosphate, catalyzed by GpsA and another glycerol-3-phosphate dehydrogenase, GlpD. Using a broad metabolomics approach, we found that GpsA serves as a dominant regulator of NADH and glycerol-3-phosphate levels in vitro, metabolic intermediates that reflect the cellular redox potential and serve as a precursor for lipid and lipoprotein biosynthesis, respectively. Additionally, GpsA was required for survival under nutrient stress, regulated overall reductase activity and controlled B. burgdorferi morphology in vitro. Furthermore, during in vitro nutrient stress, both glycerol and N-acetylglucosamine were bactericidal to B. burgdorferi in a GlpD-dependent manner. This study is also the first to identify a suppressor mutation in B. burgdorferi: a glpD deletion restored the wild-type phenotype to the pleiotropic gpsA mutant, including murine infectivity by needle inoculation at high doses, survival under nutrient stress, morphological changes and the metabolic imbalance of NADH and glycerol-3-phosphate. These results illustrate how basic metabolic functions that are dispensable for in vitro growth can be essential for in vivo infectivity of B. burgdorferi and may serve as attractive therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick

et al. 2022

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“…breve (Xiao et al, 2020). Probiotics have a significant ability to degrade host mucin, release monosaccharides or amino acids, and provide nutrients for other resident bacteria (Liang & Vallance, 2021). At the same time, mucus-degrading bacteria produce SCFA with a range of functions in the host.…”

Section: Discussionmentioning

confidence: 99%

Isolation and identification of mucin-degrading bacteria originated from human faeces and their potential probiotic efficacy according to host–microbiome enterotype

Zhou

et al. 2022

Journal of Applied Microbiology

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Aim: Mucin-degrading bacteria are known to be beneficial for gut health. We aimed to isolate human-derived mucin-degrading bacteria and identify potential probiotic characteristics and their effects on the bacterial community and short-chain fatty acid (SCFA) production according to three different enterotypes of the host. Methods and Results: Bacteria with mucin decomposition ability from human faeces were isolated and identified by 16S rRNA sequencing and MALDI-TOF. Heat resistance, acid resistance, antibiotic resistance, and antibacterial activity were analysed in the selected bacteria. Their adhesion capability to the Caco-2 cell was determined by scanning electron microscopy. Their ability to alter the bacterial community and SCFA production of the isolated bacteria was investigated in three enterotypes.The three isolated strains were Bifidobacterium(Bif.) animalis SPM01 (CP001606.1, 99%), Bif. longum SPM02 (NR_043437.1, 99%), and Limosilactobacillus(L.) reuteri SPM03 (CP000705.1, 99%) deposited in Korean Collection for Type Culture (KCTC-18958P). Among them, Bif. animalis exhibited the highest mucin degrading ability.They exhibited strong resistance to acidic conditions, moderate resistance to heat, and the ability to adhere tightly to Caco-2 cells. Three isolated mucin-degrading bacteria incubation increased Lactobacillus in the faecal bacteria from Bacteroides and Prevotella enterotypes. However, only L. reuteri elevated Lactobacillus in the faecal bacteria from the Ruminococcus enterotype. B. longum and B. animalis increased the αdiversity in the Ruminococcus enterotype, while their incubation with other intestinal types decreased the αdiversity. Bifidobacterium animalis and L. reuteri increased the butyric acid level in faecal bacteria from the Prevotella enterotype, and L. reuteri elevated the acetic acid level in those from the Ruminococcus enterotype.However, the overall SCFA changes were minimal. Conclusions:The isolated mucin-degrading bacteria act as probiotics and modulate gut microbiota and SCFA production differently according to the host′s enterotypes.

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“…Interestingly, the Δ cpxRA mutant had an increased lag phase when grown in the presence of oxidative stress in LB while growth was abolished in SCF with H 2 O 2 (Figure 5A and B). As detailed thoroughly in recent reviews, it is understood that C. rodentium utilizes aerobic respiration to outcompete host microbiota during colonization (6, 51, 52). A previous study found that deletion of the cydAB genes in C. rodentium , which are required for aerobic respiration, resulted in a severe reduction of growth in vivo (53).…”

Section: Discussionmentioning

confidence: 99%

Simulated colonic fluid replicates the in vivo growth capabilities of Citrobacter rodentium cpxRA mutants and uncovers additive effects of Cpx regulated genes on fitness

Gilliland¹,

Gavino

Gruenheid

et al. 2022

Preprint

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Citrobacter rodentium is an attaching and effacing (A/E) pathogen used to model enteropathogenic and enterohemorrhagic Escherichia coli infections in mice. During colonization, C. rodentium must adapt to stresses in the gastrointestinal tract such as antimicrobial peptides, pH changes, and bile salts. The Cpx envelope stress response (ESR) is a two-component system used by some bacteria to remediate stress by modulating gene expression and is necessary for C. rodentium pathogenesis in mice. Here, we utilized simulated colonic fluid (SCF) to mimic the gastrointestinal environment which we show strongly induces the Cpx ESR and highlights a fitness defect specific to the ΔcpxRA mutant. While investigating genes in the Cpx regulon that may contribute to C. rodentium pathogenesis, we found that the absence of the Cpx ESR resulted in higher expression of the LEE master regulator, ler, and the genes yebE, ygiB, bssR, and htpX relied on CpxRA for proper expression. We then determined that CpxRA and select gene mutants were essential for proper growth in SCF when in the presence of extraneous stressors and in competition. Although none of the Cpx-regulated gene mutants exhibited marked virulence phenotypes in vivo, the ΔcpxRA mutant had reduced colonization and attenuated virulence, as previously determined, which replicated the in vitro growth phenotypes specific to SCF. Overall, these results indicate that the ΔcpxRA virulence defect is not due to any single Cpx regulon gene examined. Instead, attenuation may be the result of defective growth in the colonic environment resulting from the collective impact of multiple Cpx-regulated genes.

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What’s for dinner? How Citrobacter rodentium’s metabolism helps it thrive in the competitive gut

Cited by 13 publications

References 48 publications

The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick

The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick

Isolation and identification of mucin-degrading bacteria originated from human faeces and their potential probiotic efficacy according to host–microbiome enterotype

Simulated colonic fluid replicates the in vivo growth capabilities of Citrobacter rodentium cpxRA mutants and uncovers additive effects of Cpx regulated genes on fitness

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