LRMoore, Univ of Southern Maine

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A Microbial Biorealm page on the genus LRMoore, Univ of Southern Maine

Classification

Higher order taxa

Bacteria; Bacteroidetes; Flavobacteriia; Flavobacteriales; Flavobacteriaceae; Capnocytophaga [Use NCBI link to find]

Species

NCBI: Taxonomy

'Capnocytophaga canimorsus'

Description and significance

Capnocytophaga canimorsus is a capnophilic (carbon dioxide loving), facultative anaerobic rod shaped Gram-negative1 nonsporeforming bacterium.6 C. canimorsus is a zoonotic agent (causes interspecies infection) that has been isolated from humans following bite wounds, licks, scratches, and general exposure to dogs5, a lesser degree in cats, and rarely rabbits.1 The bacterium was first isolated in 1976 from a human following a dog bite and was initially named CDC group dysgenic fermenter DF-2 until 1989 it was given its current name.1,6 Millions of people worldwide suffer from animal bites. It has been estimated that out of the 50% of Americans who will be bitten by an animal in their lifetime, 90% of the bites will be inflicted by both dogs and cats.1

C. canimorsus has been documented to cause wound and systemic infection in humans. Although between the years 1976-2010 only 200 cases of Capnocytophaga infection were reported, severe clinical symptoms span a wide range including, but not limited to, septicemia, meningitis, osteomylitis, peritonitis, and endocarditis.1 If exposed to the bacterium, immunocompromised, asplenic, alcoholic, aged, and chronically diseased individuals are at higher risk of contracting infection even though infection has been observed in healthy individuals.1 Exposure and identification of C. canimorsus has proven difficult due to its fastidious nature, but recent PCR-restriction fragment length polymorphism (PCR-RFLP) species specific methods have detected the commensal bacterium in the oral flora of 74% of dogs.2

According to a 2011-2012 American Pet Products Association survey there are 78.2 million dogs and 86.4 million cats owned in the United States alone which does not account for strays or shelter animals.3 The sheer number of dogs and cats warrants the study and characterization of C. canimorsus and other potential zoonotic microbes that make their home living commensally on household pets.

Genome structure

The genome of C. canimorsus Cc5, a strain isolated from a human sepsis patient, consists of a single circular replicon of 2,571,406 base pair, a guanine and cytosine content of 36.11%, and 2,405 coding sequences.4 The genome contains 46 tRNAs, three sets of rRNA, an RNase P, two tmRNAs, a TPP riboswitch, an SRP, a CRISPR region, and 206 lipoprotein genes.4

Cell and colony structure

C. canimorsus are Gram-negative fusiform or filamentous rods1 measuring 0.45-0.6 µm in diameter and 2.5-5.7 µm in length8. In blood media, longer rods, curved filaments, spindle shaped, and coccoid forms have also been observed. Colonies range from pink to yellow, are initially pin-point in size (less than 0.5 mm in diameter) and are either convex or flat.1 Flat colonies tend to be irregularly shaped while convex colonies have a narrow and flat edge. After 48 hours of incubation the colonies grow larger (3.5 mm in diameter) and are raised displaying a shiny spreading edge as well as finger-like projections for gliding motility. The bacteria have no flagella6, motors, or pili and their movement has been called surface translocation.8

Metabolism

Successful isolation of C. canimorsus is facilitated by specialized culture on heart infusion agar supplemented with 5% rabbit or sheep blood and incubation in a candle extinction jar (CO2).6 The bacterium requires high levels of iron in the culture media1 and although not obligately microaerophilic, thrives in a CO2-rich environment.6 Poor growth was recorded on routine screening media including Tryptic soy agar, Tryptic soy blood agar, LB agar8, MacConkey agar6, and triple sugar iron agar6. The anticoagulant polyanethole-sulfonate which is commonly used in automatic blood culture systems inhibits the growth of C. canimorsus.1

Biochemical testing showed C. canimorsus to differ from other Capnocytophaga species because it tested positive for oxidase and catalase1, and esculin reactions.8 C. canimorsus also tested positive for arginine dihydrolase, ơ-nitrophenyl-β-Ɗ-galactopyranoside, and alkaline phosphatase.1,6 Acid production without gas was recorded from the breakdown of the fermentable substrates Ɗ-glucose, lactose, and maltose. Other fermentable sources include dextrin, Ɗ-galactose, glycogen, Ɗ-mannose, and starch. Acid production was negative when grown in the presence of inulin, raffinose, melibiose, and sucrose. Variable reactions were observed for nitrate reduction, esculing hydrolysis, and acid production from cellibiose and fructose.

Ecology

C. canimorsus grows in the oral flora of 26-74% of canines, 18-57% of felines, and rarely rabbits.7

Pathology

The oral flora of dogs is a highly competitive feeding ground for approximately 500 different bacterial strains.9 C. canimorsus is resistant to phagocytosis and killing by macrophages and blocks the killing of unrelated bacteria by macrophages. The bacterium exhibits robust growth when in contact with mammalian cells.10

Due to sialidase and the polysaccharide utilization loci PCL5-encoded Gpd complex, C. canimorsus has been shown to sustain growth by evading host phagocytic cells and capturing amino-sugars off of their surfaces. Sialidase passes through the bacterium’s cytoplasmic membrane via the Sec pathway, crosses the outer membrane and remains attached. Although the mechanism of action is still being studied it has been shown that the Gpd genes associated with the complex consist of a specific outer membrane porin, a starch-binding protein, glycan binding proteins, and an endo-β-Ɲ-acetylglucosaminidase. The surface localized complex allows C. canimorsus to feed on glycan chains from the glycoproteins exposed on the surface of host epithelial cells and macrophages without adhering to them.10 The complex initiates a deglycosylation process for C. canimorsus metabolism. Sialidase might have evolved as a metabolic fitness factor contributing to commensalism in the canine and feline oral flora, but when the bacterium is exposed to a new host, the complex contributes to pathogenesis.5

Clinical Symptoms and Treatment

Systemic symptoms arise 5-7 days prior to a dog bite.1 Initial symptoms range from localized cellulitis, pain, purulent discharge, lymphangitis, and regional lymphadenopathy. Septicemia symptoms include chills, mylagia, vomiting, diarrhea, dyspnea, abdominal pain, malaise, mental confusion, and headache. Immunocompromised individuals exposed to the bacterium are more susceptible than healthy persons to sepsis, meningitis, osteomylitis, peritonitis, endocarditis, pneumonia, purulent arthritis, disseminated intravascular coagulation, and fulminant purpura.1

Medications that have been successful in vitro include penicillins, erythromycin, clindamycin, doxycycline, rifampin, quinolones, carbapenems, vancomycin, and third - generation cephalosporins, and amoxicillin/clavulanic acid because some beta-lactamase-producing strains have been isolated.7

References

1.Wim Gaastra, Len J.A. Lipman. Review Capnocytophaga canimorsus. Elsevier, Veterinary Microbiology 140 (2010) 339-346 [doi:10.1016/j.vetmic.2009.01.040]

2. Michio Suzuki, Masanobu Kimura, Koichi Imaoka, Akio Yamada. Prevalence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in dogs and cats determined by using a newly established species-specific PCR. Veterinary Microbiology Volume 144 Issues 1-2, 29 July 2010, Pages 172-176. [doi:10.1128/JCM.01246-09]

3. http://www.americanpetproducts.org/press_industrytrends.asp; Copyright 1998-2012 American Pet Products Association Inc.

4. Pablo Manfred, Marco Pagni, Guy R. Cornelis. Complete Genome Sequence of the Dog Commensal and Humane Pathogenic Capnocytophaga canimorsus Strain 5. Journal of Bacteriology October 2011 vol. 193 no. 19 5558-5559. [doi:10.1128/JB.05853-11.]

5. Francesco Renzi, Pablo Manfredi, Manuela Mally, Suzette Moes, Paul Jeno , Guy R. Cornelis. The N-glycan Glycoprotein Deglycosylation Complex(Gpd) from Capnocytophaga canimorsus Deglycosylates Human IgG. PLoS Pathog 7(6): e1002118. [doi:10.1371/journal.ppat.1002118]

6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC267282/pdf/jcm00062-0015.pdf Don J. Brenner, Dannie G. Hollis, G. Richard Fanning, and Robert E. Weaver. Capnocytophaga canimorsus sp. nov. (Formerly CDC Group DF-2), a Cause of Septicemia following Dog Bite, and C. cynodegmi sp. nov., a Cause of Localized Wound Infection following Dog Bite. Journal of Clinical Microbiology Vol. 27, No. 2, Feb. 1989, p. 231-235, 0095-1137/89/020231-05.

7. J. Scott Weese and Martha B. Fulford. Bacterial Diseases. Companion Animal Zoonoses. Published Online: 10 December 2010. [doi: 10.1002/9780470958957]

8. S.K. Dilegge, V.P. Edgcomb, E.R. Leadbetter, Presence of the oral bacterium Capnocytophaga canimorsus in the tooth plaque of canines, Elseiver, Veterinary Microbiology 149 (2011) 437-445 [doi:10.1016/j.vetmic.2010.12.010]

9. Manuela mally, Hwain Shin, Cécile Paroz, Regine Landmann, and Guy R. Cornelis. Capnocytophaga canimorsus A Human Pathogen Feeding at the Surface of Epithelial Cells and Phagocytes. PLoS Pathog 4(9) 2008 e1000164 [doi:10.1371/journal.ppat.1000164]

10. Hwain Shin, Manuela Mally, Salome Meyer, Chantal Fiechter, Cécile Paroz, Ulrich Zaehringer, Guy R. Cornelis. Resistance of Capnocytophaga canimorsus to Killing by Human Complement and Polymorphonuclear Leukocytes. Infect. Immun. June 2009 vol. 77 no. 6 2262-2271[doi: 10.1128/IAI.01324-08]

Edited by student of Dr. Lisa R. Moore, University of Southern Maine, Department of Biological Sciences, http://www.usm.maine.edu/bio