Capnocytophaga canimorsus resists phagocytosis by macrophages and blocks the ability of macrophages to kill other bacteria

Meyer, Salome; Shin, Hwain; Cornelis, Guy R.

doi:10.1016/j.imbio.2008.07.019

Cited by 25 publications

(23 citation statements)

References 14 publications

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“…It was shown that human macrophages incubated with C. canimorsus failed to produce tumor necrosis factor alpha, interleukin-1␣ (IL-1␣), IL-6, Il-8, and gamma interferon; that TLR-4 could not be activated by the reference strain; and that even tumor necrosis factor alpha release by another pathogen, Yersinia enterocolitica, was impaired by live C. canimorsus (21). The resistance to phagocytosis of C. canimorsus by macrophages and the blocking of the ability of macrophages to kill other bacteria also were demonstrated by the same group of investigators (17), as well as its resistance to killing by complement and polymorphonuclear leukocytes (22). However, C. canimorsus sepsis is characterized by extensive signs of inflammation, and alternative virulence mechanisms should be present.…”

Section: Discussionmentioning

confidence: 84%

Molecular Characterization of Capnocytophaga canimorsus and Other Canine Capnocytophaga spp. and Assessment by PCR of Their Frequencies in Dogs

et al. 2009

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Capnocytophaga canimorsus can be a virulent pathogen, whereas C. cynodegmi is of low virulence. Heterogeneity within these species, their frequency in dogs, and pathogenicity factors are largely unknown. Strains from blood cultures from patients presumptively identified as C. canimorsus (n ‫؍‬ 25) and as C. cynodegmi by rrs analysis (n ‫؍‬ 4), blood cultures from dogs (n ‫؍‬ 8), blood cultures from cats (n ‫؍‬ 2), and cultures from swabs from dog mouths (n ‫؍‬ 53) were analyzed. PCR-restriction fragment length polymorphism (PCR-RFLP), a species-specific PCR on rpoB, and rrs sequencing were used. All 29 strains from human blood cultures could be grouped into three PCR-RFLP types. One included the C. canimorsus type strain, and the other types were closely related. Two canine strains were C. canimorsus and grouped into the least common RLFP pattern group. Five were C. cynodegmi and clustered with the reference strain. One canine and both feline strains were distinct. Four human strains that presumptively had been identified as C. cynodegmi by RNA gene sequence analysis clustered with the C. canimorsus strains by both PCR-RFLP and the sequence-specific PCR of the rpoB gene. C. canimorsus DNA was present in 73% (range, 61 to 85%) of dogs' mouths, and C. cynodegmi DNA was present in 96% (range, 94 to 100%) of dogs' mouths. As defined by rpoB PCR-RFLP and by PCRs using specific primers, all strains from human blood were C. canimorsus. The sequencing of rrs genes suggested the presence of different gene copies in a few strains, indicating that the method is less appropriate for species identification. Both species are present in the majority of dogs. Additional Capnocytophaga species occur in dogs' and cats' mouths.

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Section: Discussionmentioning

confidence: 84%

Molecular Characterization of Capnocytophaga canimorsus and Other Canine Capnocytophaga spp. and Assessment by PCR of Their Frequencies in Dogs

et al. 2009

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“…Recent observations help understanding the infectiveness of C. canimorsus for humans. C. canimorsus manifest some resistance to phagocytosis by human polymorphonuclear leukocytes and detection by macrophages1213, which results in a lack of release of pro-inflammatory cytokines14. Like many Gram-negative pathogens, C. canimorsus resist the bactericidal activity of 10% human or rabbit serum1315 but they are nevertheless killed by undiluted fresh serum or blood1617.…”

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confidence: 99%

Evidence for a LOS and a capsular polysaccharide in Capnocytophaga canimorsus

Renzi

Ittig

Sadovskaya

et al. 2016

Sci Rep

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Capnocytophaga canimorsus is a dog’s and cat’s oral commensal which can cause fatal human infections upon bites or scratches. Infections mainly start with flu-like symptoms but can rapidly evolve in fatal septicaemia with a mortality as high as 40%. Here we present the discovery of a polysaccharide capsule (CPS) at the surface of C. canimorsus 5 (Cc5), a strain isolated from a fulminant septicaemia. We provide genetic and chemical data showing that this capsule is related to the lipooligosaccharide (LOS) and probably composed of the same polysaccharide units. A CPS was also found in nine out of nine other strains of C. canimorsus. In addition, the genomes of three of these strains, sequenced previously, contain genes similar to those encoding CPS biosynthesis in Cc5. Thus, the presence of a CPS is likely to be a common property of C. canimorsus. The CPS and not the LOS confers protection against the bactericidal effect of human serum and phagocytosis by macrophages. An antiserum raised against the capsule increased the killing of C. canimorsus by human serum thus showing that anti-capsule antibodies have a protective role. These findings provide a new major element in the understanding of the pathogenesis of C. canimorsus.

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“…In addition, live Cc5 cells downregulate the expression of Toll-like receptor 4 and dephosphorylate p38 mitogen-activated protein kinase (31). C. canimorsus cells also resist phagocytosis by a murine macrophage cell line, and some strains, like Cc5, even block the killing of unrelated preys like Escherichia coli by macrophages (23).…”

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confidence: 99%

Resistance ofCapnocytophaga canimorsusto Killing by Human Complement and Polymorphonuclear Leukocytes

et al. 2009

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Capnocytophaga canimorsus is a bacterium of the canine oral flora known since 1976 to cause rare but severe septicemia and peripheral gangrene in patients that have been in contact with a dog. It was recently shown that these bacteria do not elicit an inflammatory response (H. Shin, M. Mally, M. Kuhn, C. Paroz, and G. R. Cornelis, J. Infect. Dis. 195:375-386, 2007). Here, we analyze their sensitivity to the innate immune system. Bacteria from the archetype strain Cc5 were highly resistant to killing by complement. There was little membrane attack complex (MAC) deposition in spite of C3b deposition. Cc5 bacteria were as resistant to phagocytosis by human polymorphonuclear leukocytes (PMNs) as Yersinia enterocolitica MRS40, endowed with an antiphagocytic type III secretion system. We isolated Y1C12, a transposon mutant that is hypersensitive to killing by complement via the antibody-dependent classical pathway. The mutation inactivated a putative glycosyltransferase gene, suggesting that the Y1C12 mutant was affected at the level of a capsular polysaccharide or lipopolysaccharide (LPS) structure. Cc5 appeared to have several polysaccharidic structures, one being altered in Y1C12. The structure missing in Y1C12 could be purified by classical LPS purification procedures and labeled by tritiated palmitate, indicating that it is more likely to be an LPS structure than a capsule. Y1C12 bacteria were also more sensitive to phagocytosis by PMNs than wild-type bacteria. In conclusion, a polysaccharide structure, likely an LPS, protects C. canimorsus from deposition of the complement MAC and from efficient phagocytosis by PMNs.

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Capnocytophaga canimorsus resists phagocytosis by macrophages and blocks the ability of macrophages to kill other bacteria

Cited by 25 publications

References 14 publications

Molecular Characterization of Capnocytophaga canimorsus and Other Canine Capnocytophaga spp. and Assessment by PCR of Their Frequencies in Dogs

Molecular Characterization of Capnocytophaga canimorsus and Other Canine Capnocytophaga spp. and Assessment by PCR of Their Frequencies in Dogs

Evidence for a LOS and a capsular polysaccharide in Capnocytophaga canimorsus

Resistance ofCapnocytophaga canimorsusto Killing by Human Complement and Polymorphonuclear Leukocytes

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