Article 30 years of study of Kingella kingae: post tenebras, lux CERONI, Dimitri, et al. Abstract Kingella kingae is a Gram-negative bacterium that is today recognized as the major cause of joint and bone infections in young children. This microorganism is a member of the normal flora of the oropharynx, and the carriage rate among children under 4 years of age is approximately 10%. K. kingae is transmitted from child to child through close personal contact. Key virulence factors of K. kingae include expression of type IV pili, Knh-mediated adhesive activity and production of a potent RTX toxin. The clinical presentation of K. kingae invasive infection is often subtle and may be associated to mild-to-moderate biologic inflammatory responses, highlighting the importance a high index of suspicion. Molecular diagnosis of K. kingae infections by nucleic acid amplification techniques enables identification of this fastidious microorganism. Invasive infections typically respond favorably to medical treatment, with the exception of cases of endocarditis, which may require urgent valve replacement. Reference CERONI, Dimitri, et al. 30 years of study of Kingella kingae: post tenebras, lux. Future Microbiology, 2013, vol. 8, no. 2, p. 233-45 DOI : 10.2217/fmb.12.144 PMID : 23374128 Available at: http://archive-ouverte.unige.ch/unige:33314 Disclaimer: layout of this document may differ from the published version. 1 / 1 For reprint orders, please contact: [email protected] Review 30 years of study of Kingella Microbiology Future kingae: post tenebras, lux Dimitri Ceroni*1, Victor Dubois-Ferrière1, Abdessalam Cherkaoui2, Léopold Lamah1, Gesuele Renzi2, Pierre Lascombes1, Belaieff Wilson1 & Jacques Schrenzel2,3 1Paediatric Orthopaedic Service, University of Geneva Hospitals, 6 Rue Willy-Donzé, 1211 Geneva 14, Switzerland 2Clinical Microbiology Laboratory, Service of Infectious Diseases, University of Geneva Hospitals, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland 3Genomic Research Laboratory, Service of Infectious Diseases, University of Geneva Hospitals, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland *Author for correspondence: [email protected] Kingella kingae is a Gram-negative bacterium that is today recognized as the major cause of joint and bone infections in young children. This microorganism is a member of the normal flora of the oropharynx, and the carriage rate among children under 4 years of age is approximately 10%. K. kingae is transmitted from child to child through close personal contact. Key virulence factors of K. kingae include expression of type IV pili, Knh-mediated adhesive activity and production of a potent RTX toxin. The clinical presentation of K. kingae invasive infection is often subtle and may be associated to mild-to-moderate biologic inflammatory responses, highlighting the importance a high index of suspicion. Molecular diagnosis of K. kingae infections by nucleic acid amplification techniques enables identification of this fastidious microorganism. Invasive infections typically respond favorably to medical treatment, with the exception of cases of endocarditis, which may require urgent valve replacement. Historical review the family Neisseriaceae; it has since been known Kingella kingae is a species of gram-negative as K. kingae [7,8]. In the same year, two additional aerobic coccobacilli, which belongs to the family species, Kingella oralis and Kingella denitrificans, Neisseriaceae. This organism was initially referred were added to the Kingella genus [9]. Finally, in to as Moraxella new species 1 [1,2] or group M 2005, Lawson et al. reported the isolation and organisms [1,3]. The first description of the characterization of a hitherto-unknown Gram- bacterium, later to become known as K. kingae, negative, rod-shaped Neisseria-like organism was made in the 1960s by Elizabeth King, an from an infected wound resulting from a bite American bacteriologist of the US CDC. In from a kinkajou [10]. Based on both phenotypic 1968, Henriksen and Bovre formally described and phylogenetic evidence, it was proposed the new Moraxella species, analyzing nine strains that the unknown organism be classified as (including two obtained from Elisabeth King) a new species, Kingella potus. Currently, the that had been isolated from blood, joint fluid, Kingella genus therefore consists of four species: bone, nose and throat [4]. All isolates were K. kingae, K. denitrificans, K. potus and K. oralis. characterized by b-hemolysis, acid production from glucose and maltose and a lack of catalase Microbiologic features activity [4]. The authors distinguished this new Bacterial characteristics microorganism from all other known Moraxella K. kingae is a coccoid, medium-sized rectilinear species, and named it Moraxella kingii in honor rod, appearing as pairs or short chains of short of Elisabeth King [4]. A further taxonomic bacilli with tapered ends [4,11]. K. kingae is an b modification was made in 1974, when the isolate aerobic and facultative, anaerobic -hemolytic Keywords was renamed Moraxella kingae [5]. This change bacterium that is Gram negative, with some to the feminine gender reflected the naming of tendency to resist decolorization [6]. The isolate n bacteremia n colonization the organism after the female scientist. Although is nonmobile and has no endospores; contrary n endocarditis n invasive infections n Kingella kingae Kingella organisms shared several characteristics to the initial assumption, a recent paper suggests n oropharyngeal carriage with Moraxella species, DNA homology studies that K. kingae elaborates a surface-associated n osteoarticular infection n PCR assays n RTX toxin revealed sufficient differences to suggest the polysaccharide capsule [12]. On the basis of studies need for a separate genus [6]. The final change in by Henriksen and Bovre [13], many characteristics nomenclature was thus made in 1976, when the of K. kingae have been recognized; for example, organism was assigned to the genus Kingella in K. kingae is oxidase positive and exhibits negative part of 10.2217/FMB.12.144 © 2013 Future Medicine Ltd Future Microbiol. (2013) 8(2), 233–245 ISSN 1746-0913 233 Review Ceroni, Dubois-Ferrière, Cherkaoui et al. catalase, urease and indole reaction. It produces strains circulate within the pediatric population, acid from glucose and maltose, but not from a small subset is responsible for most clinical other sugars, hydrolyzes indoxyl phosphate and infections, and only a few exhibit significant l-propyl-b-naphthylamide and, finally, shows associations with particular clinical diseases positive alkaline and acid phosphatase reactions [20]. A recent study demonstrated that only five [4,11,13,14]. K. kingae grows on trypticase soy strains (B, H, K, N and P) caused 72.9% of all agar with added hemoglobin (blood agar) and invasive infections [19,20]. Clone K exhibits an chocolate agar, but fails to grow on MacConkey optimal balance between transmissibility and or Krigler media [15]. A selective medium invasiveness, and it is significantly associated consisting of blood agar with 2 µg/ml of added with bacteremia. Clone N shows remarkable tis- vancomycin has been developed to inhibit the sue invasiveness and it is responsible for arthri- growth of competing Gram-positive flora and tis and osteomyelitis. The genome from septic facilitate recognition of K. kingae in respiratory arthritis strains has been recently sequenced; specimens [16]. A CO2-enriched atmosphere K. kingae strain PYKK081 is recognized to enhances growth [11], but only a small proportion cause infections of the skeletal system in young of strains is truly capnophilic (requires CO2 for children [25], but may also be responsible for its growth) [17]. K. kingae is relatively fastidious infective endocarditis in children and adults. in its growth requirements. It is an aerobe that K. kingae strain 11220434 is another strain that grows optimally at 33–37°C. Growth at room is responsible for acute arthritis [26]. Finally, temperature (20°C) is slight. Growth is adequate clone P organisms are strongly associated with on both nutrient and blood agar, and this bacterial endocarditis [20]. organism has no requirement for X (hemin) and V (nicotinamide adenine dinucleotide) factors. Oropharyngeal carriage of K. kingae Normal oropharyngeal flora Member of the HACEK group The normal flora of the oropharynx contains a K. kingae is the fifth member of the HACEK large number of regular bacterial inhabitants. group. The acronym HACEK refers to a The most important group of microorganisms grouping of Gram-negative bacilli that forms a native to this body niche are the a-hemolytic normal part of the human flora: Haemophilus streptococci. This group includes Streptococcus species, Aggregatibacter actinomycetemcomitans, mitis, Streptococcus mutans, Streptococcus milleri Cardiobacterium hominis, Eikenella corrodens and Streptococcus salivarius. It is believed that and Kingella species. All of these Gram-negative these bacteria act as antagonists against invasion bacteria are part of the normal oropharyngeal by pathogenic streptococci. Additionally, cultures flora, which grow slowly, prefer a carbon dioxide- from this region usually show large numbers of enriched atmosphere and share an enhanced diphtheroids, Moraxella (formerly Branhamella) capacity to produce endocarditis, especially catarrhalis, Neisseria species and HACEK in children and young adults. Based on large organisms, such as Kingella. Invasive infections reviews,