Capnocytophaga

Taxonomy

The genus Capnocytophaga consists of fermentative capnophilic bacteria that morphologically appear as fusiform thin to slender gram-negative bacilli with tapered ends. The genus currently consists of nine species— C. canimorsus, C. canis, C. cynodegmi, C. gingivalis, C. granulosa, C. haemolytica, C. leadbetteri, C. ochracea, C. sputigena —that can be subdivided into two major groups associated with the oral microbiota of humans and animals. A tenth and eleventh reputed species, C. stomatis and C. endodontalis, have been recovered from animals and human infections and a periapical abscess, respectively. All validated species or taxa are recognized human pathogens or implicated in causing disease. Phylogenetically, the genus Capnocytophaga resides in the family Flavobacteriaceae. The complete genomes of six different Capnocytophaga spp. have been sequenced more recently.

Pathogenesis and Clinical Manifestations

Few studies have focused on which virulence factors are important in oral-associated Capnocytophaga infections. Oral-associated Capnocytophaga organisms produce a number of cell-bound or extracellular factors that may promote progression of periodontitis by enhancing the growth of bacteria in plaques and subgingival pockets or by evading host immune responses. Such factors include immunoglobulin A1 (IgA1) protease, phospholipase A ₂ , aminopeptidases, and type IX secretion system as well as the ability to form biofilms and chemotaxis-guided (gliding) motility.

Progress has been made in understanding potential pathogenicity mechanisms functional in zoonosis-associated invasive infections typified by fulminant C. canimorsus septicemia. These mechanisms can be broadly categorized into four areas: (1) failure of C. canimorsus to trigger innate immune responses based on resistance to complement-mediated lysis and evasion of phagocytosis by macrophages; (2) inability of Toll-like receptor 4 to respond to C. canimorsus with activation of proinflammatory responses including generation of tumor necrosis factor, cytokines (interleukin-6), chemokines (interleukin-8), and nitric oxide ; (3) expression of cell surface lipoproteins (polysaccharide utilization loci) and sialidase, which deglycosylate host glycoproteins (including human IgG), leading to bacterial growth and persistence in vivo; and (4) a modified lipid A and lipopolysaccharide architecture that may affect endotoxicity and binding to human myeloid differentiation factor 2.

More recent studies indicate that only a subset of C. canimorsus strains may be highly pathogenic for humans. Of nine known capsular serotypes of C. canimorsus, serotypes A, B, and C predominate, causing almost 90% of human infections. In contrast, these serotypes are found at a much lower frequency (7.6%) in the oral microbiota of dogs. This fact may help account for the relatively low frequency of C. canimorsus infections in people after dog bites.

Human Capnocytophaga infections can be broken down into five major categories: (1) septicemia, (2) diseases of the central nervous system (CNS), (3) eye infections, (4) illnesses associated with pregnancy, and (5) miscellaneous complications including infections of bone and tissue. Although most Capnocytophaga infections occur in individuals with impaired immune function or with significant underlying disease, infections in healthy individuals have been well documented.