Multilocus Sequence Typing and rtxA Toxin Gene Sequencing Analysis of Kingella kingae Isolates Demonstrates Genetic Diversity and International Clones

Basmaci, Romain; Yagupsky, Pablo; Ilharreborde, Brice; Guyot, Kathleen; Porat, Nurith; Chomton, Marilyn; Thiberge, Jean‐Michel; Mazda, Keyvan; Bingen, Édouard; Bonacorsi, Stéphane; Bidet, Philippe

doi:10.1371/journal.pone.0038078

Cited by 48 publications

(87 citation statements)

References 20 publications

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“…All K. kingae clinical strains possess the rtxA toxin gene, making this gene a relevant target to diagnose K. kingae infection by PCR. However, there is a polymorphism of the rtxA gene, which encodes the RTX toxin [48], and a few studies have demonstrated that the most virulent strains of the species harbored a 33-bp duplication or triplication in their rtxA sequence, suggesting that this genetic trait could represent a genetic determinant of virulence [48,49]. Finally, Bendaoud et al reported that K. kingae forms biofilms in a microtiter plate assay [50].…”

Section: Rtx Toxin Productionmentioning

confidence: 99%

“…On this subject, a recent study demonstrated that five clones of K. kingae (B, H, K, N and P) were responsible for the majority of the invasive infections, exhibiting genetic stability, long-term persistence and wide geographic dispersal [20]. Recently, an animal model has been developed and may contribute to the discrimination between highand low-virulence clones in the future, and would point to clones to be further investigated in order to identify genetic determinants of virulence [49]. …”

Section: Future Perspectivementioning

confidence: 99%

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30 Years of Study of Kingella Kingae : Post Tenebras , Lux

et al. 2013

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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

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Section: Rtx Toxin Productionmentioning

confidence: 99%

Section: Future Perspectivementioning

confidence: 99%

30 Years of Study of Kingella Kingae : Post Tenebras , Lux

et al. 2013

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“…Recent studies have revealed that K. kingae organisms display remarkable genomic variability [40,41] and profound strain-to-strain differences in terms of invasive capability [42,43]. Characterization of isolates by PFGE and multilocus sequence typing demonstrated that some clones are frequently isolated from healthy carriers but are seldom if ever detected in patients with invasive diseases, whereas others are common etiology of clinical infections and show significant association with syndromes such as bacteremia, skeletal system infections, or endocarditis [42,43].…”

Section: From Colonization To Clinical Diseasementioning

confidence: 99%

Respiratory Colonization by Kingella kingae, Person-to-Person Transmission, and Pathogenesis of Invasive Infection

Yagupsky¹

2013

TOIDJ

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Increasing recognition of Kingella kingae as an important pathogen of early childhood in recent years has elicited interest in the study of the asymptomatic carriage of the organism, its dissemination in the human population, and the role played by colonization of the upper respiratory tract in the pathogenesis of K. kingae invasion of the skeletal system and the endocardium.Research has revealed that K. kingae is a frequent component of the normal oropharyngeal microbiota, disclosed the subtle molecular mechanisms responsible for adherence of the bacterium to the pharyngeal mucosa, and revealed the presence of a potent RTX toxin, probably implicated in breaching the epithelial barrier, survival of the organism in the bloodstream, and damage to bone and joint tissues. Epidemiological studies have shown that carriage of K. kingae peaks in 6-30 month-old children, coinciding with the age of increased susceptibility to invasive disease, and daycare-center attendance represent a significant risk factor for pharyngeal colonization. The organism is transmitted from person-toperson by close contact between family members, playmaytes, and day-care center attendees. Carriage is characterized by frequent turnover of colonizing strains, similar to what has been described in other pathogens of respiratory origin.

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“…Genetic typing of K. kingae isolates was recently performed with different molecular methods, including multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), singlelocus polymorphisms of the rtxA gene encoding the RTX toxin (13,14), and the por gene that encodes the bacterial porin (15). The typing results revealed noticeable genomic heterogeneity in the species.…”

mentioning

confidence: 99%

“…The typing results revealed noticeable genomic heterogeneity in the species. To date, 40 MLST sequence types (STs) and 73 PFGE clones have been identified, as well as 18 rtxA and 12 different por alleles (13)(14)(15)(16)(17)(18). Remarkable congruence has been observed between the results obtained using different typing methods (16,18).…”

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Major Intercontinentally Distributed Sequence Types of Kingella kingae and Development of a Rapid Molecular Typing Tool

et al. 2014

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f Although Kingella kingae is the most common etiology of osteoarticular infections in young children, is a frequent cause of bacteremia in those younger than 4 years, and has been involved in clusters of invasive infections among daycare center attendees, the population structure of the species has not been systematically studied. Using multilocus sequence typing, we investigated the genetic diversity of the largest intercontinental collection of K. kingae strains to date. To facilitate typing of bacterial isolates, we developed a novel genotyping tool that targets the DNA uptake sequence (DUS). Among 324 strains isolated from asymptomatic carriers and patients from Israel, Europe, North America, and Australia with various invasive forms of the disease from 1960 to 2013, we identified 64 sequence types (STs) and 12 ST complexes (STcs). Five predominant STcs, comprising 72.2% of all strains, were distributed intercontinentally. ST-6 was the most frequent, showing a worldwide distribution, and appeared genotypically isolated by exhibiting few neighboring STs, suggesting an optimal fitness. ST-14 and ST-23 appeared to be the oldest groups of bacteria, while ST-25 probably emerged more recently from the highly evolutive ST-23. Using the DUS typing method, randomly chosen isolates were correctly classified to one of the major STcs. The comprehensive description of K. kingae evolution would help to detect new emerging clones and decipher virulence and fitness mechanisms. The rapid and reproducible DUS typing method may serve in the initial investigation of K. kingae outbreaks.

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Multilocus Sequence Typing and rtxA Toxin Gene Sequencing Analysis of Kingella kingae Isolates Demonstrates Genetic Diversity and International Clones

Cited by 48 publications

References 20 publications

30 Years of Study of Kingella Kingae : Post Tenebras , Lux

30 Years of Study of Kingella Kingae : Post Tenebras , Lux

Respiratory Colonization by Kingella kingae, Person-to-Person Transmission, and Pathogenesis of Invasive Infection

Major Intercontinentally Distributed Sequence Types of Kingella kingae and Development of a Rapid Molecular Typing Tool

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