General | Carbohydrate O/F | Substrate utilisation | Enzymes | Metabolites | Antibiotics

Overview


  • Citrobacter freundii is a Gram-negative, non-spore-forming, aerobic, motile, rod-shaped bacterium. It has been detected in at least 19 gut microbiome compilation studies or metastudies. The DNA G+C content is 50-51%. Citrobacter freundii is probably a common, although minor, coloniser of the gut. (Farmer1985; Monteverde1944; Young1971; Friederiksen2005Bergey)



  • This organism has been recovered from human faeces (high load in several ulcerative colitis patients), sewage, animals and clinical sources (blood, wound, urine - CCUG). The risk classification (www.baua.de) for this organism is 2, i.e., risk of individual infection, but low risk of spread. It is an opportunistic pathogen. Is a known gut commensal. Robust growth can have negative consequences for gut health.

  • QUIRKS
  • In 6% of Europeans (unseenbio.com), i.e., a minor coloniser.

  • GENERAL CHARACTERISTICS (Farmer1985); (Monteverde1944); (Young1971); (Friederiksen2005Bergey);
    Character Response
  • ±
  • Strain-dependent hydrolysis or digestion:
  • arginine;
  • H+
  • Acid from carbohydrates usually produced:
  • arabinose; L-arabinose; glucose; mannose; rhamnose; xylose; lactose; maltose; mucate; melibiose; trehalose; glycerol; mannitol; sorbitol; 5-ketogluconate;
  • Substrates assimilated or utilised:
  • N-acetylglucosamine; L-arabinose; cellubiose; fructose; fucose; galactose; gluconate; gentiobiose; glucose; glycerol; lactose; maltose; maltotriose; mannitol; mannose; melibiose; rhamnose; ribose; raffinose; sorbitol; sorbose; sucrose; trehalose; xylose; alanine; D-alanine; δ-aminovalerate; aspartate; glutamate; proline; serine; tyrosine; acetate; aconitate; citrate; fumarate; DL-glycerate; 3-hydroxybutyrate; 3-hydroxybenzoate; 2-ketogluconate; 5-ketogluconate; DL-lactate; L-malate; mucate; phenylpropionate; saccharate; succinate; L-tartrate; meso-tartrate; methyl-β-glucoside; methyl-α-galactoside; methyl-β-galactoside; glutamine; D-glucuronate; D-malate; m-coumarate; gentisate; tricarballylate;
  • ±
  • Strain-dependent substrate utilisation:
  • dulcitol; ethanolamine; inositol; D-lyxose; methyl-α-glucoside; 2-ketoglutarate; phenylacetate; maltitol; lactulose; palatinose; putrescine;
  • Active enzymes:
  • catalase; β-galactosidase;
  • ±
  • Strain-dependent active enzymes:
  • urease;

  • SPECIAL FEATURES (Farmer1985); (Arens1997); (Monteverde1944); (Young1971); (Friederiksen2005Bergey);
    Character Response
  • Metabolites produced:
  • H₂S;
  • Metabolites not produced:
  • indole;
  • Methyl red test:
  • active
  • VP test:
  • activity is variable
  • ONPG test:
  • active
  • KCN growth:
  • growth observed
  • NO3➔NO2:
  • reduced
  • Pigments:
  • not produced

  • RESPONSE TO ANTIBIOTICS (Arens1997); (Friederiksen2005Bergey); (Kumar1978); (Citron1997);
    Class Active Resistant
  • Penicillins:
  • amoxicillin-clavulanic acid; doripenem; ertapenem; imipenem; meropenem; piperacillin; piperacillin-tazobactam; ticarcillin;
  • amoxicillin; ampicillin; ampicillin-sulbactam; cloxacillin; methicillin; oxacillin; penicillin; penicillin G; ticarcillin-clavulanic acid;
  • Cephalosporins:
  • cefazolin; cefepime; cefotetan; ceftazidime; moxalactam;
  • cefaclor; cefadroxil; cefalexin; cefixime; cefpodoxime; cefprozil; ceftizoxime; cefuroxime; cephalothin;
  • Macrolides:
  • erythromycin;
  • Tetracyclines:
  • tigecycline;
  • tetracycline;
  • Quinolines:
  • ciprofloxacin; clinafloxacin; gatifloxacin; levofloxacin; moxifloxacin; ofloxacin; pefloxacin; sparfloxacin; trovafloxacin;
  • Aminoglycosides:
  • amikacin; gentamicin; kanamycin; neomycin; netilmycin; streptomycin;
  • Heterocycles:
  • chloramphenicol; fosfomycin; nitrofurantoin; sulfamethoxazole;
  • fusidic-acid; trimethoprim; trimethoprim-sulfamethoxazole;
  • Vancomycins:
  • vancomycin;
  • Miscellaneous antibiotics:
  • polymyxin B;
  • clindamycin; lincomycin;

  • N/A

  • With the abuse of antibiotics, C. freundii has become resistant to common antibiotics, causing great challenges to the clinical treatment of infections. Genes, such as parC, parE, and gyrA, were detected in the genome, showing resistance to fluoroquinolones; the _-lactamase gene ampC, the MATE family of multidrug resistance (MDR) efflux pumps, and multidrug major facilitator super family (MFS) genes were also found in the genome. [PMID: 26893430]

  • GutFeeling KnowledgeBase COMMENTS [Website]

    Citrobacter freundii is a Gram-negative, aerobic, and short-rod bacterium and is commonly present in the gut microbiota in humans and other animals. It is an opportunistic pathogen that causes diarrhea, septicemia, meningitis, and urinary tract infections, especially in immunocompromised people. P10159 strain was isolated from the urine samples from a patient with esophageal carcinoma in China. [PMID: 26893430]

  • Finegold, S. M., Howard, R. A., & Vera, L. S. (1974). Effect of diet on human intestinal fecal flora: comparison of Japanese and American diets. Am. J. Clin. Nutr, 27, 1456–1469.


  • Details


    GENERAL
    Lineage Physiology General Growth Tolerances Hydrol./digest./degr.
    Phylum:  Proteobacteria Class:  Gammaproteobacteria Order:  Enterobacterales Family:  Enterobacteriaceae Genus:  Citrobacter Gram stain:  neg O2 Relation.:  aerobic Spore:  No spore Motility:  Swimming Morphology:  Rod Pigment:  neg
    Health:   Negative
    Source:  human faeces (high load in several ulcerative colitis patients), sewage, animals and clinical sources (blood, wound, urine - CCUG)
    DNA G+C(%):  50-51
    Urea:  neg Gelatin:  neg Arginine:  d DNA:  neg

    CARBOHYDRATE ACID FORMATION
    Monosaccharide O/F Oligosaccharide O/F Polysaccharide O/F Polyol O/F Other O/F
    Arabinose:  + L-Arabinose:  + Glucose:  + Mannose:  + Rhamnose:  + Xylose:  + Cellubiose:  vr Lactose:  + Maltose:  + Melibiose:  + Sucrose:  vr Trehalose:  + Aesculin:  neg Adonitol:  neg D-Arabitol:  neg L-Arabitol:  neg Dulcitol:  vr Erythritol:  neg Glycerol:  + Inositol:  vr Mannitol:  + Sorbitol:  + 5-Ketogluconate:  + Me-α-D-Glc:  neg Salicin:  neg

    SUBSTRATE ASSIMILATION & UTILISATION
    Monosaccharide util/assim Oligosaccharide util/assim Other carboh. util/assim Amino acid util/assim Organic acid util/assim
    L-Arabinose:  + Fructose:  + Fucose:  + Galactose:  + Glucose:  + D-Lyxose:  d Mannose:  + Rhamnose:  + Ribose:  + Sorbose:  + D-Tagatose:  neg Xylose:  + Cellubiose:  + Gentiobiose:  + Lactose:  + Maltose:  + Maltotriose:  + Melezitose:  neg Melibiose:  + Raffinose:  + Sucrose:  + D-Turanose:  neg Trehalose:  + N_Acetyl_glucosamine:  + Adonitol:  neg D-Arabitol:  neg L-Arabitol:  neg Dulcitol:  d Erythritol:  neg Aesculin:  neg Ethanolamine:  d Gluconate:  + Glycerol:  + Inositol:  d Mannitol:  + Me-α-D-Glc:  d Sorbitol:  + Xylitol:  neg Ala:  + D-Ala:  + 4-Aminobutyrate:  vr 5-Aminovalerate:  d(+) Asp:  + Betaine:  neg Glu:  + Histamine:  neg His:  neg Pro:  + Ser:  + Trigonelline:  neg Tryptamine:  neg Trp:  neg Tyr:  d(+) Acetate:  d(+) Aconitate:  cis(+) trans(neg) Benzoate:  neg Caprate:  neg Caprylate:  neg Citrate:  + Fumarate:  + Glutarate:  neg DL-Glycerate:  + 3-Hydroxybutyrate:  + 3-Hydroxybenzoate:  + 4-Hydroxybenzoate:  neg Itaconate:  neg 2-Ketogluconate:  + 5-Ketogluconate:  + DL-Lactate:  + L-Malate:  + Malonate:  neg Mucate:  + Phenylacetate:  d Phenylpropionate:  d(+) Propionate:  vr Quinate:  neg Saccharate:  + Succinate:  + D-Tartrate:  neg L-Tartrate:  d(+)

    ENZYME ACTIVITY
    Enzymes: General Enzymes: Carbohydrate Enzymes: Protein Enzymes: Arylamidases Enzymes: Esters/fats
    Oxidase:  neg Catalase:  + Urease:  d Ac-β-glcamnd:  neg α-Galactosidase:  vr β-Galactosidase:  + α-Glucosidase:  neg β-Glucosidase:  neg β-Glucuronidase:  neg LysDC:  neg OrnDC:  neg Phe deaminase:  neg DNAse:  neg Lipase:  neg

    METABOLITES - PRODUCTION & USE
    Fuel Usable Metabolites Metabolites Released Special Products Compounds Produced

    H2S:  + Indole:  d(neg) Pigment:  neg

    ANTIBIOTICS ℞
    Penicillins & Penems (μg/mL) Cephalosporins (μg/mL) Aminoglycosides (μg/mL) Macrolides (μg/mL) Quinolones (μg/mL)
    amoxicillin:  Res
    Augmentin:  S(MIC50): 8, MIC90: 16, RNG: (4–16)
    ampicillin:  R(8)
    amp-sulb:  Res
    aztreonam:  Var(MIC50): >0.12, MIC90: >16, RNG: (0.12->16)
    cloxacillin:  Res
    methicillin:  Res
    oxacillin:  Res
    penicillin:  R(1024)
    penicillin_G:  Res
    piperacillin:  Var(MIC50): 2, MIC90: 32, S(16)
    piper-taz:  S(≤1/4)
    ticarcillin:  Var(MIC50): 2, MIC90: 128, S
    tica-clav:  R(MIC50): >32, MIC90: >32, RNG: (>32)
    doripenem:  Sens
    ertapenem:  S(MIC50): 0.008, MIC90: 0.25, RNG: (0.008-4)
    imipenem:  S(MIC50): 0.5, MIC90: 2, S(4)
    meropenem:  S(MIC50): 0.016, MIC90: 0.031, RNG: (0.016-0.031)
    cefaclor:  R(MIC50): 32, MIC90: >64, RNG: (8->64)
    cefadroxil:  Res
    cefalexin:  R(>128)
    cefazolin:  S(8,vr)
    cefdinir:  Var(MIC50): 1, MIC90: 128, RNG: (0.125->128)
    cefepime:  S(8,vr)
    cefixime:  R, MIC90: R, RNG: (0.12->4)
    cefoperazone:  Var(MIC50): 0.5, MIC90: 128, RNG: (0.06->128)
    cefotaxime:  Var(MIC50): 0.06, MIC90: 32, Var(8)
    cefotetan:  S(MIC50): 0.5, MIC90: 0.5, RNG: (0.5)
    cefoxitin:  Var(MIC50): 2, MIC90: 64, RNG: (1–64)
    cefpodoxime:  Res
    cefprozil:  R(MIC50): 64, MIC90: >64, RNG: (8->64)
    ceftazidime:  S(≤0.5/≤0.5)
    ceftizoxime:  Res
    cefuroxime:  R(8)
    cephalothin:  Res
    moxalactam:  S(0.25/0.5)
    amikacin:  S(MIC50): 2, MIC90: 8, RNG: (0.5-32)
    gentamicin:  S(MIC50): 0.5, MIC90: 0.5, RNG: (0.5)
    kanamycin:  S(30)
    neomycin:  S(10)
    netilmycin:  S(MIC50): -, MIC90: 1
    streptomycin:  S(25)
    tobramycin:  Var(MIC50): 4, MIC90: 32
    erythromycin:  R(10)
    ciprofloxacin:  S(MIC50): 0.015, MIC90: 0.015, RNG: (0.015–0.06)
    clinafloxacin:  S(MIC50): 0.008, MIC90: 0.06, RNG: (0.008-0.06)
    gatifloxacin:  S(MIC50): 0.03, MIC90: 1, RNG: (0.03->4)
    levofloxacin:  S(MIC50): 0.015, MIC90: 0.015, RNG: (0.015–0.03)
    moxifloxacin:  S(MIC50): 0.12, MIC90: 4, RNG: (0.03->16)
    nalidixic-acid:  Var(MIC50): 4, MIC90: 16, RNG: (4->32)
    ofloxacin:  S(MIC50): 0.25, MIC90: 4, S(2)
    pefloxacin:  Sens
    sparfloxacin:  S(MIC50): 0.12, MIC90: 1, RNG: (0.06-1)
    trovafloxacin:  S(MIC50): 0.06, MIC90: 4, RNG: (<0.008->16)
    Tetracyclines (μg/mL) Vancomycin Class (μg/mL) Polypep/ketides (μg/mL) Heterocycles (μg/mL) Other (μg/mL)
    minocycline:  Var(MIC50): >2, MIC90: >8, RNG: (0.5->8)
    tetracycline:  Res
    tigecycline:  S(MIC50): 0.25, MIC90: 0.5, RNG: (0.25-4)
    vancomycin:  Res
    chloramphenicol:  Sens
    fosfomycin:  Sens
    nitrofurantoin:  S(32)
    sulfamethoxazole:  S(200)
    trimethoprim:  R(19.5)
    SXT:  Res
    co-trimoxazole:  Var(MIC50): 2, MIC90: 38
    clindamycin:  Res
    lincomycin:  Res
    polymyxin_B:  Sens
    fusidic-acid:  Res

    References


    SPECIFIC REFERENCES FOR CITROBACTER FREUNDII
  • Farmer1985 - Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens.
  • Arens1997 - Differentiation and susceptibility of Citrobacter isolates from patients in a university hospital.
  • Monteverde1944 - A New Type of the Salmonella Genus.
  • Young1971 - Levinea, a New Genus of the Family Enterobacteriaceae.
  • Friederiksen2005Bergey - Bergey's manual of systematic bacteriology. Vol. 2, The Gammaproteobacteria Part B. Family Enterobacteriaceae, Genus X. Citrobacter
  • Kumar1978 - Enterobacteria of emerging pathogenic significance from clinical cases in man and animals and detection of toads and wall lizards as their reservoirs.
  • Gao2020 - Functional Microbiomics Reveals Alterations of the Gut Microbiome and Host Co-Metabolism in Patients With Alcoholic Hepatitis
  • Adams2011 - Gastrointestinal flora and gastrointestinal status in children with autism - comparisons to typical children and correlation with autism severity
  • Gryp2020 - Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients
  • Citron1997 - Comparative in vitro activities of trovafloxacin (CP-99,219) against 221 aerobic and 217 anaerobic bacteria isolated from patients with intra-abdominal infections.
  • ...............................
  • GUT MICROBIOME COMPILATIONS AND METASTUDIES FOR CITROBACTER FREUNDII
  • Almeida2019 - A new genomic blueprint of the human gut microbiota.
  • Benno1984 - The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants.
  • Benno1986 - Comparison of the fecal microflora in rural Japanese and urban Canadians.
  • Benno1989 - Comparison of fecal microflora of elderly persons in rural and urban areas of Japan.
  • Byrd2020 - Stability and dynamics of the human gut microbiome and its association with systemic immune traits.
  • Chen2020 - Structural and Functional Characterization of the Gut Microbiota in Elderly Women With Migraine
  • Chen2020a - Featured Gut Microbiomes Associated With the Progression of Chronic Hepatitis B Disease
  • Dubinkina2017 - Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease
  • Finegold1977 - Fecal microbial flora in Seventh Day Adventist populations and control subjects.
  • Forster2019 - A human gut bacterial genome and culture collection for improved metagenomic analyses.
  • Hu2019 - The Gut Microbiome Signatures Discriminate Healthy From Pulmonary Tuberculosis Patients
  • Jie2017 - The gut microbiome in atherosclerotic cardiovascular disease
  • King2019 - Baseline human gut microbiota profile in healthy people and standard reporting template.
  • Lagier2016 - Culture of previously uncultured members of the human gut microbiota by culturomics.
  • New2022 - Collective effects of human genomic variation on microbiome function.
  • Pfleiderer2013 - Culturomics identified 11 new bacterial species from a single anorexia nervosa stool sample.
  • RajilicStojanovic2014 - The first 1000 cultured species of the human gastrointestinal microbiota.
  • Wang2020a - Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents
  • Zou2019 - 1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses.
  • ...............................
  • GENERAL REFERENCES FOR CITROBACTER FREUNDII
  • CCUG - Culture Collection University of Gothenburg - Entire Collection
  • Alkhalil2017 - Bacterial involvements in ulcerative colitis: molecular and microbiological studies