KINGELLA

                                            Compiled by: Zenisha Acharya

                                            Central Department of Microbiology

                                            Tribhuvan University, Kirtipur

       Kingella kingae is a species of Gram-negative facultative anaerobic β-hemolytic coccobacilli.

       In the 1960s Elizabeth O. King, working at the U.S. Centers for Disease Control (CDC) in Atlanta, GA, described a novel bacterial species isolated from human respiratory secretions, blood, and bone and joint exudates.

       The organism, initially assigned to the genus Moraxella and designated Moraxella kingii in honor of King’s seminal research, was later placed in a separate genus and renamed Kingella kingae.

            Taxonomy

       The genus Kingella belongs to the Neisseriaceae family in the beta subclass of the Proteobacteria and comprises four recognized species:

  • K. denitrificans, which has been implicated in cases of bacteremia, endocarditis, pleural empyema, pediatric vaginitis, chorioamnionitis, and granulomatous disease in AIDS patients.

    K. oralis, which is a commensal dweller of the human buccal cavity and is associated with dental plaque and periodontitis.

    K. potus, a zoonotic organism recovered from an infected bite

    Although K. kingae’s taxonomic place remained uncertain for many years, subsequent analysis of its biochemical profile and fatty acid composition and genotypic studies have led to the conclusion that K. kingae constitutes a separate species, only distantly linked to other Neisseriaceae.

kingella kingae

       Scientific classification

       Domain:          Bacteria

       Phylum:          Proteobacteria

       Class:              Betaproteobacteria

       Order:              Neisseriales

       Family:           Neisseriaceae

       Genus:             Kingella

       Species:            K. kingae

       Binomial name

       Kingella kingae

 

Identification
Kingella kingae appears as pairs or chains of 4 to 8 plump (0.6 to 1by 1 to 3) micrometer coccobacilli.

Kingella kingae cells tend to resist decolorization, and thus the organism may be erroneously identified as Gram positive, but electron microscopic examination discloses a characteristic Gram-negative cell wall structure.

The bacterium is beta-hemolytic, non-motile, and non-spore forming, exhibits negative catalase, urease, and indole tests with rare exceptions, has oxidase activity.

Produces acid from glucose and usually from maltose, hydrolyzes indoxyl phosphate and L-prolyl-beta-naphthylamide, and exhibits positive alkaline and acid phosphatase reactions.

Basic Characteristics         Properties (Kingella kingae)
10% Bile                               Negative (-ve)
Capsule                                 Positive   (+ve)
Catalase                                Negative (-ve)
Citrate                                   Negative (-ve)
Coagulase                             Negative (-ve)
Gas                                        Negative (-ve)
Gelatin Hydrolysis               Negative (-ve)
Gram Staining                      Gram-negative
H2S                                       Variable
Hemolysis                             Positive (+ve)
Indole                                   Negative (-ve)
Motility                                Negative (-ve)
6% NaCl                               Negative (-ve)
Nitrate Reduction                 Negative (-ve)
Nitrite Reduction                 Negative (-ve)
OF                                         Fermentative
Oxidase                                 Positive (+ve)
Shape                                    Coccobacilli (0.6 to 1
μm by 1 to 3 μm)
Spore                                    Negative (-ve)
Urease                                   Negative (-ve)

DNase                                   Negative (-ve)
Fructose                                Negative (-ve)
Galactose                              Negative (-ve)
Glucose                                 Positive (+ve)
Glycerol                                Negative (-ve)
Inositol                                 Negative (-ve)
Lactose                                 Negative (-ve)
Maltose                                 Positive (+ve)
Mannitol                               Negative (-ve)
Mannose                               Negative (-ve)
Raffinose                              Negative (-ve)
Rhamnose                             Negative (-ve)
Salicin                                  Negative (-ve)
Sorbitol                                 Negative (-ve)
Starch                                   Negative (-ve)
Sucrose                                 Negative (-ve)
Trehalose                              Negative (-ve)
Xylose                                  Negative (-ve)

Culture
K kingae is a facultative anaerobic bacterium that grows on conventional Trypticase-soy agar supplemented with 5% hemoglobin (blood agar medium), chocolate agar, Columbia-based blood agar, and GC-based media.
Similar to the case for other Neisseriaceae, most K. kingae strains can be recovered on Thayer Martin medium but do not develop on MacConkey or Krigler agar.
Many isolates show poor growth on the cation-supplemented Mueller-Hinton medium used to determine the antibiotic susceptibility of the species.
Similar to the case for other bacteria that inhabit the respiratory tract, growth is improved in a 5% CO2 atmosphere, but only a minute proportion of isolates are strictly capnophilic.
Growth on solid media is characterized by marked pitting of the agar surface, which is best seen after removal of the colony.

Kingella kingae strains produce three different colony types that are associated with the degree of pilus expression:
a spreading corroding morphology distinguished by a small central colony encircled by a wide fringe,
a non-spreading /non corroding type consisting of a flat colony surrounded by a narrow fringe, and a dome-shaped colony with no noticeable fringe.
The first two morphologies are associated with the presence of long fimbriae, whereas strains growing as domed colonies are non piliated.
The ability to produce the spreading-corroding type of morphology can be irreversibly lost after repeated subculture.

Cultural characteristics on 5% sheep blood agar(35 degree c/5%co2)
K kingae : small, with a small zone of beta hemolysis; may pit agar
K denitrificans :
small, non-hemolytic; frequently pits agar; can grow on a N gonorrhoeae selective 

agar( e.g. Thyer martin agar)

                                                                                           

VIRULENCE FACTORS

Pili:
The expression of pili in K. kingae appears to be finely regulated by three genes (54 gene, pilS, and pilR)
Pili are essential for the adherence of the bacterium to the respiratory epithelium and synovial layer.

Polysaccharide Capsule
Synthesis of polysaccharide capsules is a convergent evolutionary strategy shared by many important human pathogens that colonize the upper respiratory tract.
Capsules are lipid-anchored, outer-membrane-associated, and surface-exposed structures that confer protection from phagocytosis and complement-mediated killing. Capsules are crucial virulence factors that enable bacterial survival on the mucosal surfaces by thwarting the host's defensive response.

Exopolysaccharides and Biofilm Production
Protects the organism from the deleterious effects of the immune response, desiccation, and antimicrobial drugs. K. kingae exopolysaccharides facilitate colonization of the pharyngeal epithelium by inhibiting biofilm production by other organisms competing for the same niche. It is also plausible that these exopolysaccharides play a role in the regulation of the periodic release of K. kingae cells from the biofilm matrix, enabling dissemination of the bacterium by droplet transmission.

RTX Toxin
Kingella kingae RTX toxin is a 100-kDa protein that appears to be secreted in the extracellular environment in a soluble form, as well as a component of outer membrane vesicles (OMVs) that are internalized by host's cells.

Mostly all the invasive K. kingae isolates studied so far produce RTX toxin, whereas it is  absent in the less virulent K. denitrificans and K. oralis, suggesting that this bacterial constituent is universally conserved in K. kingae because it improves colonization fitness by disrupting the oropharyngeal epithelium. Also RTX toxin enable survival of K. kingae in the bloodstream and invasion of the skeletal system tissues and therefore have a disease-promoting effect.

PATHOGENESIS OF DISEASE:
Transmission
:  spread person-to-person through respiratory secretions and saliva. Transmission is more likely in child care settings because young children are more likely to harbor the bacteria.
Incubation period:  People can spread K kingae if the bacteria are present in their respiratory secretions. Children younger than four years are more likely to carry the bacteria without symptoms (colonized) and have higher numbers of bacteria than older children and adults. Older children and adults are usually colonized for only a short period.

The pathogenesis of disease caused by K. kingae is believed to begin with colonization of the posterior pharynx. The process of colonization involves adherence to respiratory epithelial cells, which is mediated in vitro at least in part by type IV pili that are composed primarily of a major pilin subunit called PilA1.

The PilA1 protein shares homology with the major pilin subunit in type IV pili expressed by other bacterial pathogens, including Pseudomonas aeruginosa PilA, N meningitidis PilE, and Neisseria gonorrhoeae PilE. In addition, K. kingae pili contain 2 minor pilus-associated proteins referred to as PilC1 and PilC2, which seem to play complementary roles and influence the efficiency of adherence to respiratory epithelial cells. After colonization of the posterior pharynx, K. kingae   invade the epithelium to enter the bloodstream.

K. kingae produces a potent extracellular toxin that belongs to the RTX family of toxins and is capable of lysing epithelial, synovial, and macrophage cells. This toxin facilitate disruption of the respiratory epithelium.
Once in the bloodstream, it evade a variety of host defense mechanisms. It produce an extracellular polysaccharide capsule that facilitates resistance to serum-killing activity and opsonophagocytosis.

CLINICAL PRESENTATION OF K kingae INFECTIONS:
Invasive K. kingae disease usually affects previously healthy children aged less than 4 years, whereas older children and adults frequently having predisposing conditions such as failure to thrive , congenital heart disease, prolonged corticosteroid therapy, primary immunodeficiency, hematological malignancies, liver cirrhosis, end-stage renal disease, sickle cell anemia, diabetes mellitus, cardiac valve pathology, systemic lupus erythematosus, rheumatoid arthritis, renal transplants , solid tumors, or AIDS

Skeletal System Infections
K kingae septic arthritis generally involves large joints such as the knee, hip, ankle, or shoulder. K kingae osteomyelitis usually affects the long bones, involvement of the calcaneus, talus, sternum, or clavicle occur.

Bacteremia
K kingae bacteremia without evidence of endocarditis has been observed primarily in children. The duration of symptoms before diagnosis ranges from 1 to 7 days, and the mean maximal fever is 39.0°C

Endocarditis
K kingae is included in the HACEK (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) group of organisms that is collectively responsible for up to 5% of cases of bacterial endocarditis.

In contrast to other K kingae infections, endocarditis has been diagnosed primarily in older children and adults. In approximately one-half of patients the infection affects a native valve. A predisposing cardiac malformation or rheumatic heart disease is observed.

Typically, the left side of the heart is involved, usually the mitral valve. In general, fever and acute phase reactants are more elevated in patients with endocarditis.
Despite the remarkable susceptibility of K kingae to antibiotics, cardiac failure, septic shock, mycotic aneurisms, pulmonary infarctions, meningitis, cerebrovascular accidents, and other life threatening complications are common, and the overall mortality rate is 16%.

Lower Respiratory Tract Infections
K kingae has been isolated from the blood or pleural fluid of previously healthy and immunocompromised adult and pediatric patients with
epiglottitis, laryngotracheobronchitis, pneumonia, or pyothorax, which suggests that the organism may cause lower respiratory tract infections.

Soft Tissue Infections
:
A diversity of soft tissue infections, including cellulitis , tenosynovitis and dactylitis, bursitis, and subcutaneous, intramuscular abscesses is caused by bacteria.

Occult Bacteremia:

Isolation of Kingella kingae from the blood without evidence of endocarditis or another nidus of infection has been reported repeatedly in children and exceptionally in adults and this syndrome represents the second most frequent expression of K. kingae disease in pediatric patients.

Mild to moderate fever is usually recorded, and the mean leukocyte count frequently is less than 15* 10^9 /liter

Ocular Infections:

palpebral abscess, keratitis, corneal ulcer, endophthalmitis, orbital cellulitis and periorbital cellulitis are common infection.

Other Infections:
Anecdotal cases of K. kingae pericarditis, peritonitis, urinary tract infection, and apthous-stomatitis have been also reported in adult patients.


EPIDEMIOLOGY OF INVASIVE K. KINGAE DISEASE:

K kingae colonizes the human tonsills and is rarely isolated from the nasopharynx.
Colonization does not usually start before the age of 6 months. The carriage rate gradually increases thereafter, reaching a prevalence rate of 9-12% in the second year of life, declines in older children, and is close to nil in adults.The colonized pharyngeal surfaces are the source of infectious fomites that disseminate the organism between young family members and playmates. Carriage and transmission are enhanced in daycare center attendance among whom clusters of invasive K. kingae disease have been reported, especially in the context of a concomitant upper respiratory viral infection or stomatitis.  It is plausible that increased drooling induced by buccal ulcers facilitates the dissemination of the bacterium among young children with poor hygienic habitat.

Invasive K. kingae diseases are almost limited to young children.
Over 95% of cases occur below the age of 5 years and an annual incidence rate of 9.4/100,000 infections has been reported in this population group, although because of the suboptimal culture detection of the organism.
Kingella kingae infections are exceptional in the first 6 months of age suggesting that maternal antibodies confer protection against both colonization and disease in early infancy. Most affected young patients are otherwise healthy, whereas older children and adults often have immunosuppressing conditions, malignancy, or antecedent cardiac valve pathology. Although the carriage rate remains remarkably constant along the year, invasive K. kingae infections are most common during late fall and early winter, coinciding with the seasonal increase of viral upper respiratory infection.


DIAGNOSIS
Diagnosis of K kingae infection may be challenging due to the fastidious nature of the organism in culture. Evaluation of cardiac, bone, joint tissue, or fluid by PCR is a useful tool for the diagnosis of some cases of K kingae infection.
Sample: depends on the site of infection
Blood, pleural fluid, bone aspirate
Direct detection method:
Gram’s stain: other than this method there is no direct detection methods for this bacteria
kingella stain as short plump, coccobacilli with squared-off ends that may forms chains.
Transportation:
inoculated swabs should be kept at room temperature in Amies or similar transport medium and promptly sent to the laboratory for further processing

Cultivation
Trypticase-soy agar supplemented with 5% hemoglobin (blood agar medium), chocolate agar, Columbia-based blood agar, and GC-based media.
Most K. kingae strains can be recovered on Thayer Martin medium
cultural characteristics and biochemical properties: as mentioned earlier

NOTE: K denitrificans may be mistaken for N. gonorrhoeae when isolated from Modified Thyer-Martin agar. Nitrate reduction test is key for differentiating K denitrificans from N gonorrhoeae, which is nitrate negative.

Detection by Molecular Methods:
In recent years, novel molecular detection assays have enabled diagnosis of K. kingae infections in patients for whom cultures of joint exudates on routine media does not reveal the presence of the bacterium.
The PCR-based strategy has been also implemented in investigations of K. kingae’s carriage and the relationship between respiratory colonization and clinical disease.

The RTX toxin is produced by all K. kingae strains examined so far, the encoding RTX locus genes appear to be appropriate targets for detecting the organism in the blood, synovial fluid, and solid tissues, as well as in upper respiratory tract specimens.

Serodiagnosis
This technique is generally not used for laboratory diagnosis of infection caused by K kingae.

PREVENTION:
Since this organism does not posses threat for human health, there are no such recommended vaccination or prophylaxis protocols.
Good hand washing and respiratory etiquette are important. Cleaning of toys, tables, and other surfaces that could be contaminated with respiratory secretions can help prevent the spread of Kingella kingae and other germs. During outbreaks in child care centers, antibiotics can be used to reduce the number of children who are colonized with Kingella kingae and prevent additional infections. If prescribed antibiotics, take them as directed.

TREATMENT

Antibiotic Susceptibility K kingae is almost always highly susceptible to penicillins and cephalosporins, although -lactamase production has been reported in rare isolates.

With few exceptions, K kingae is also susceptible to aminoglycosides, macrolides, trimethoprim, sulfamethoxazole, tetracyclines, chloramphenicol, and fluoroquinolones.

The empirical drug therapy for skeletal infections in children usually consists of intravenous administration of oxacillin/nafcillin or a second or third-generation cephalosporin while pending culture results.

In areas in which community-associated methicillin-resistant Staphylococcus aureus is prevalent, a combination of a beta-lactam antibiotic and vancomycin is recommended.

REFERENCES

https://www.ndhealth.gov/Disease/Documents/faqs/Kingella.pdf

file:///C:/Users/default.DESKTOP-S673BEP/Documents/medical/Bailey_&_Scott_s_Diagnostic_Microbiology_12th_Edition(1).pdf

https://cmr.asm.org/content/cmr/28/1/54.full.pdf

 

 

 

 

 

 

 

 

 

 

 

 

 


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