Capnocytophaga

Capnocytophaga
Scientific classification
Domain:	Bacteria
Phylum:	Bacteroidota
Class:	Flavobacteriia
Order:	Flavobacteriales
Family:	Flavobacteriaceae
Genus:	Capnocytophaga; Brenner et al. 1990
Species
	C. canimorsus ; C. cynodegmi ; C. gingivalis ; C. granulosa ; C. haemolytica ; C. leadbetteri ; C. ochracea ; C. sputigena Contents Taxonomy ; Bacteriological isolation and identification ; Pathogenicity ; Resistance to antibiotics ; The CfxA group of beta-lactamases ; The CSP-1 beta- lactamase ; The beta- lactamases CepA/CblA ; Other acquired resistance ; Treatment of infections ; References ; Further reading ;

Last updated March 31, 2023

Capnocytophaga is a genus of Gram-negative bacteria. Normally found in the oropharyngeal tract of mammals, they are involved in the pathogenesis of some animal bite wounds and periodontal diseases.^[2]

Taxonomy

The term Capnocytophaga comes from "capno-" for its dependence on CO₂ and "cytophaga" for its flexibility and mobility shift (gliding motility). It belongs to the family Flavobacteriaceae, order Flavobacteriales. This genus includes eight different species: C. ochracea, C. gingivalis, C. granulosa, C. haemolytica, C. sputigena, C. leadbetteri (isolated oral cavity of humans), C. canimorsus, and C. cynodegmi (isolated from the oral cavity of animals). Many strains have also been described whose classification remains uncertain.

Bacteriological isolation and identification

Capnocytophaga spp. are fusiform Gram-negative bacilli, and are part of the oral commensal flora. Microscopic observation revealed a high degree of polymorphism, with a variation in the size and appearance depending on the strain and culture conditions. This polymorphism is also reflected in the observation of colonies (orange-pigmented colonies, spreading on agar, etc.). Capnocytophaga spp. are capnophilic bacteria; they can live only in environments where the concentration of carbon dioxide is greater than that of the atmosphere (at least 5% CO₂). They can also grow anaerobically. They require enriched media, type blood agar, incubated at 37 °C. The isolation of strains of Capnocytophaga from polymicrobial samples is also possible on selective media containing antibiotics.^[3]^[4]

The identification is carried out through various biochemical tests, used for the identification of Gram-negative bacterial species, and rapid determination of enzymatic reactions. The diagnosis is delayed because of the slow and difficult growth of Capnocytophaga (48 to 72 hours). The molecular techniques (16S rDNA PCR and sequencing), and mass spectrometry appear as attractive methods for reliable identification to the genus. The identification at the species level remains difficult when a single method is used.

Pathogenicity

Capnocytophaga is a commensal genus considered as an opportunistic pathogen. These bacteria are involved in different types of infections, the severity of which depends on the immune status of the patient. In the literature, cases were reported in immunocompromised and immunocompetent patients. In immunocompetent patients, these bacteria belong to the oral bacterial community responsible for periodontal infections affecting and destroying the supporting tissues of teeth (periodontal tissue). Capnocytophaga strains are often isolated from periodontal pockets, but also from apical and periodontal abscesses, in association with other bacterial periodontal species. This condition increases alveolar bone loss, attachment loss, tooth mobility, and finally tooth loss.^[5] It can cause other diseases widely reported in the literature, such as bacteremia (potentially complicated by septic shock), infections of the musculoskeletal system (osteomyelitis, arthritis), lung (empyema, lung abscess), digestive (peritonitis), maternal-fetal (ovarian abscess, chorioamnionitis), eye (conjunctivitis), heart (endocarditis) or brain (meningitis). Capnocytophaga is clinically important in pediatric oncology and hematology,^[6]> especially when patients are in aplasia.^[7]C. canimorsus and C. cynodegmi are commonly transmitted by dog bites and known to cause sepsis, potentially complicated by thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, in immunocompromised patients^[8]

Resistance to antibiotics

Capnocytophaga spp. are usually susceptible to antibiotics, but the emergence of beta-lactam-resistant strains has been observed as early as 1980. Genes for antibiotic resistance have gradually spread among other pathogenic bacterial species by horizontal gene transfer.^[9] Susceptibility to various beta-lactam antibiotics has been described as variable depending on the strain of Capnocytophaga.^[10] This resistance is often linked to the production of beta- lactamases. Most beta-lactamases identified in Bacteroides, Prevotella, and Capnocytophaga belong to the Ambler class A. Several beta-lactamases encoded by the chromosome or a plasmid and associated with mobile genetic elements have been described in Capnocytophaga spp. The most common are: CfxA, CfxA2, CepA, CblA, and/or CSP-1.^[10]^[11]^[4]

The CfxA group of beta-lactamases

Capnocytophaga spp. can be resistant to third-generation cephalosporins, but remain susceptible to imipenem, cefoxitin, and amoxicillin combined with clavulanic acid.^[10] Although resistant strains are most frequently isolated in oral cavities, their prevalence is worrying, (Jolivet-Gougeon et al., 2008; Sixou et al., 2006). The CfxA broad spectrum beta- lactamases (CfxA, CfxA2 and CfxA3) belong to the group 2e of Bush classification. This class includes beta-lactamase enzymes with significant activity against cephalosporins and monobactams, rather than penicillins. Following the characterization of CfxA beta- lactamase in B. vulgatus and CfxA2 beta-lactamase in P. intermedia (nucleotide Genbank under accession number AF118110), a new group 2e of Bush classification named CfxA3 (nucleotide GenBank under accession number AF472622) has been characterized in C. ochracea E201 (Jolivet-Gougeon et al. 2004). The cfxA3 gene has 99% identity with cfxA of B. vulgatus and cfxA2 of P. intermedia. The analysis of the 966 bp nucleotide sequence showed that the gene encoding beta-lactamase CfxA3 in C. ochracea E201 differs from cfxA gene of B. vulgatus by substitution of two amino acids (K272E and Y239D) and from cfxA2 gene of P. intermedia by a substitution of one amino acid (Y239D). CfxA3 was different from CfxA2 because of an aspartic acid in place of tyrosine (at position 239) and from CfxA because of a glutamic acid instead of a lysine (at position 272).

The CSP-1 beta- lactamase

In 2005, Handal et al. (2005b) identified a novel Ambler class A beta-lactamase called CSP-1 from a NOR C. sputigena strain, resistant to amoxicillin and first and second generation cephalosporins. The new beta- lactamase had 32% homology with CfxA, 41% with CblA and 38% with CepA. CSP-1 is encoded by the blaCSP -1 gene (GenBank nucleotide sequence under accession number GQ217533). The GC content (38%) of this gene, its genetic environment, the lack of conjugal transfer and its detection in two reference strains suggest that it is an intrinsic resistance gene located on chromosome.^[4]

The beta- lactamases CepA/CblA

CepA (Chromosomal cephalosporinase from Bacteroides fragilis belonging to Ambler class A) is an endogenous cephalosporinase A described in Bacteroides fragilis. This beta- lactamase is ubiquitous, but frequently inactive. CepA is encoded by the cepA gene, most frequently vertically transferred (Boente et al. 2010). CblA (Chromosomal beta-lactamase from Bacteroides uniformis belonging to Ambler class A) is a specific endogenous cephalosporinase described in B. uniformis, susceptible to clavulanic acid. The homology is 43% between protein sequences CepA and CblA and 51% between nucleotide sequences. A comparison with protein sequence alignment by cepA with other beta- lactamases reveals the conservation of at least four common elements of Ambler class A.^[12]

Other acquired resistance

According to studies, different sensitivities were reported for macrolides, rifampin, quinolones, metronidazole, vancomycin, and aminoglycosides, but the mechanism involved is not precisely described.^[9]

Treatment of infections

The high frequency of strains producing beta-lactamase limit the use of single beta-lactam antibiotics as first-line treatment, which underlies the need to test the in vitro susceptibility of clinical isolates. Many antimicrobial treatments were used despite a lack of randomized trials and guidelines relating to the duration of treatment according to infected sites. The imipenem/cilastatin, clindamycin, or combinations containing an inhibitor of beta-lactamases (i.e. Augmentin, Unasyn) are always effective and their use can be recommended.^[9]^[13] For Capnocytophaga canimorsus , the drug of choice is penicillin G, given with or without a beta-lactamase inhibitor depending on resistance.^[14]

Related Research Articles

Beta-lactamases, (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

β-lactam antibiotics are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and carbacephems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds. The first β-lactam antibiotic discovered, penicillin, was isolated from a strain of Penicillium rubens.

Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

Clavulanic acid is a β-lactam drug that functions as a mechanism-based β-lactamase inhibitor. While not effective by itself as an antibiotic, when combined with penicillin-group antibiotics, it can overcome antibiotic resistance in bacteria that secrete β-lactamase, which otherwise inactivates most penicillins.

Moraxella catarrhalis is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the infection of the host cell by sticking to the host cell using trimeric autotransporter adhesins.

Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Imipenem</span> Chemical compound

Imipenem is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus play a key role in the treatment of infections not readily treated with other antibiotics.

Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

<span class="mw-page-title-main">Sultamicillin</span> Chemical compound

Sultamicillin, sold under the brand name Unasyn among others, is an oral form of the penicillin antibiotic combination ampicillin/sulbactam. It is used for the treatment of bacterial infections of the upper and lower respiratory tract, the kidneys and urinary tract, skin and soft tissues, among other organs. It contains esterified ampicillin and sulbactam.

Bacteroides fragilis is an anaerobic, Gram-negative, pleomorphic to rod-shaped bacterium. It is part of the normal microbiota of the human colon and is generally commensal, but can cause infection if displaced into the bloodstream or surrounding tissue following surgery, disease, or trauma.

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, but can cause illness in humans. 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, even grave, 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.

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.

Enterobacter cloacae is a clinically significant Gram-negative, facultatively-anaerobic, rod-shaped bacterium.

<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

Well studied Periodontal pathogens are bacteria that have been shown to significantly contribute to periodontitis.

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Anaerobic infections are caused by anaerobic bacteria. Obligately anaerobic bacteria do not grow on solid media in room air ; facultatively anaerobic bacteria can grow in the presence or absence of air. Microaerophilic bacteria do not grow at all aerobically or grow poorly, but grow better under 10% carbon dioxide or anaerobically. Anaerobic bacteria can be divided into strict anaerobes that can not grow in the presence of more than 0.5% oxygen and moderate anaerobic bacteria that are able of growing between 2 and 8% oxygen. Anaerobic bacteria usually do not possess catalase, but some can generate superoxide dismutase which protects them from oxygen.

<span class="mw-page-title-main">Antibiotic resistance in gonorrhea</span>

Neisseria gonorrhoeae, the bacterium that causes the sexually transmitted infection gonorrhea, has developed antibiotic resistance to many antibiotics. The bacteria was first identified in 1879.

References

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↑ Ehrmann E, Jolivet-Gougeon A, Bonnaure-Mallet M, Fosse T (October 2013). "Antibiotic content of selective culture media for isolation of Capnocytophaga species from oral polymicrobial samples". Letters in Applied Microbiology. 57 (4): 303–9. doi:10.1111/lam.12112. PMID 23725093. S2CID 206168867.
1 2 3 Guillon H, Eb F, Mammeri H (May 2010). "Characterization of CSP-1, a novel extended-spectrum beta-lactamase produced by a clinical isolate of Capnocytophaga sputigena". Antimicrobial Agents and Chemotherapy. 54 (5): 2231–4. doi:10.1128/AAC.00791-09. PMC 2863690 . PMID 20308380.
↑ McGuire, Michael K.; Nunn, Martha E. (1996). "Prognosis Versus Actual Outcome. III. The Effectiveness of Clinical Parameters in Accurately Predicting Tooth Survival". Journal of Periodontology. 67 (7): 666–674. doi:10.1902/jop.1996.67.7.666. PMID 8832477.
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↑ Sixou JL, Aubry-Leuliette A, De Medeiros-Battista O, Lejeune S, Jolivet-Gougeon A, Solhi-Pinsard H, Gandemer V, Barbosa-Rogier M, Bonnaure-Mallet M (March 2006). "Capnocytophaga in the dental plaque of immunocompromised children with cancer". International Journal of Paediatric Dentistry. 16 (2): 75–80. doi:10.1111/j.1365-263X.2006.00697.x. PMID 16430520.
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