Capnocytophaga canimorsus

Capnocytophaga canimorsus is a fastidious, slow-growing, Gram-negative rod of the genus Capnocytophaga. It is a commensal bacterium in the normal gingival flora of canine and feline species. Transmission may occur through bites, licks, or even close proximity with animals. C. canimorsus generally has low virulence in healthy individuals, but has been observed to cause severe illness in persons with pre-existing conditions. The pathogenesis of C. canimorsus is still largely unknown, but increased clinical diagnoses have fostered an interest in the bacillus. Treatment with antibiotics is effective in most cases, but the most important yet basic diagnostic tool available to clinicians remains the knowledge of recent exposure to canines or felines. Capnocytophaga canimorsus was first observed in 1976 by Bobo and Newton. The pair isolated a previously unknown Gram-negative bacterium from a patient presenting with meningitis in addition to sepsis. The patient had been previously exposed to two canine bites on two consecutive days from two different dogs. Noting the coincidence between the timing of the bites with the onset of symptoms, Butler et al. analyzed 17 similar cases of patients presenting with either sepsis or meningitis from 1961-1975. The cases had been sent to the CDC for examination due to the presence of an unknown Gram-negative bacillus isolated from infected individuals. Butler notified the CDC of the high incidence of dog bites in connection with the infections. The CDC could not identify the organism, so they applied the name CDC group DF-2. DF-2 stands for dysgonic fermenter, meaning that the bacterium is a slow-growing, fermentative bacillus. In 1989, while analyzing the properties of the unknown bacterium, Weaver et al. noted many similarities to bacteria of the genus Capnocytophaga. Later that same year, Brenner et al. proposed the name Capnocytophaga canimorsus after examining the morphology, G+C% content, and motility of the species. In the United States, 50% of Americans will be bitten by dogs during the course of their lifetimes; 1 million Americans are bitten by dogs annually. Cases of human infection following exposure to C. canimorsus have been observed worldwide. Cases have been reported in the United States, Canada, Europe, Australia and S. Africa. Symptoms may appear within 2–3 days after exposure, or up to 4 weeks later. Middle-aged and elderly persons are at greater risk for contraction of disease; more than 60% of sufferers are 50 years of age or older. In addition, individuals who spend a greater portion of their time with canines and felines are also at higher risk. This includes veterinarians, breeders, pet owners, and keepers. Having certain pre-existing medical conditions exacerbates the risk. Chance of infection by any bacterial species after dog bites varies between 3 and 20%; for cats, it may be as high as 50%. C. canimorsus is a fastidious, Gram-negative, fermentative, nonspore-forming rod. Bacilli are usually 1-3 μm in length. After growth on agar plates, longer rods tend to have a curved shape. The bacteria do not have flagella, but move with a gliding motion, although this can be difficult to see. C. canimorsus requires the right medium for growth. The bacterium cultures well on blood agar plates (heart infusion agar with 5% sheep or rabbit blood) and chocolate agar plates. Colonies may not be visible for up to 48 hours due to slow growth. At 18 hours, colonies are usually less than 0.5 mm in diameter, and are spotty and convex. At 24 hours, colonies may be up to 1 mm in diameter. After 48 hours, colonies are narrow, flat, and smooth, with spreading edges. At this time, colonies may appear to be purple, pink, or yellow, but once they are scraped from the agar plate, they are always yellow in appearance. The genome of C. canimorsus strain Cc5 consists of a single circular chromosome of 2,571,406 bp with a G+C content of 36.11%, and it encodes 2,405 open reading frames. The Cc5 genome contains 46 tRNAs, three sets of rRNA, an RNase P, two tmRNAs, a TPP riboswitch, and a signal recognition particle, and it contains one CRISPR region. It does not encode any type III, IV, or VI secretion systems, which are commonly linked to pathogenesis. The annotated genome sequence of Cc5 was deposited in GenBank under accession number CP002113. Members of the genus Capnocytophaga are found in the oral cavities of humans and animals. Most of these species are not found in humans. C. canimorsus is a commensal bacterium found in dogs and cats; it is not a member of the normal microbiota of humans. About 26% of dogs carry these commensal bacteria in their mouths. C. canimorsus rarely causes disease symptoms in animals. One case of C. canimorsus isolated from a dog bite wound on a small dog's head has been reported; the bacteria were localized to the wound and the dog did not present with bacteremia. A few cases of infection have been reported in rabbits after being bitten by dogs. Clinical manifestations of C. canimorsus in rabbits causes a range of symptoms, including disseminated intravascular coagulation, cellular necrosis (tissue death), low blood pressure, gangrene, and kidney failure. In addition to those at higher risk of developing complications from C. canimorsus due to greater contact with felines and canines, certain pre-existing conditions place individuals in a critically high-risk category. Among these are those who have undergone a splenectomy, alcoholics, and individuals with immunosuppression due to the use of steroids such as glucocorticoids. Individuals with β-thalassemia and smokers are also listed as high-risk. These individuals, like asplenics and alcoholics, have increased levels of alimentary iron in their bloodstream. C. canimorsus requires large amounts of iron to grow, so these conditions are optimal for the bacillus. Of the cases presented in literature, 33% occurred in asplenic individuals, who have decreased IgM and IgG production. They also have delayed macrophage assembly and produce less tuftsin. Tuftsin is responsible for the stimulation of phagocytosis, so its decrease in the presence of bacterial infection poses a problem. A functional spleen is important for the removal of pathogens. Because this particular pathogen seems to flourish in asplenic patients, both IgM antibodies and tuftsin may be critical in the process of marking this bacterium for destruction by phagocytosis. Asplenics often have double the amount of healthy iron in their bloodstreams, and are 60 times more at risk of developing fatal clinical manifestations of the bacterium. Individuals with asplenia often experience symptom onset within a day of exposure. The infection rapidly progresses toward multiple organ system failures and finally death. The mortality rate in individuals with asplenia is much higher than any other at risk-category for C. canimorsus infections.