Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 15367

Special Issue Editors


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Guest Editor
Clinical Microbiology Laboratory, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva 8410500, Israel
Interests: pediatric infectious diseases; Kingella kingae infections; human brucellosis
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Guest Editor
Hôpital Robert-Debré, Paris, France
Interests: Kingella kingae; genomics; molecular detection; invasive diseases

Special Issue Information

Dear Colleagues,

During the three decades following the first description of Kingella kingae, the organism was considered an exceptional cause of human infection, usually associated with bacterial endocarditis in adult patients. The serendipitous discovery that inoculation of skeletal system exudates into blood culture vials enhanced the recovery of this fastidious organism led to the recognition that K. kingae was an important invasive pathogen of early childhood. The development and implementation of nucleic acid amplification tests further improved its laboratory detection and established K. kingae as the prime etiology of septic arthritis, osteomyelitis, intervertebral disk infections, and hematogenous tenosynovitis in children aged 6-48 months. Recent studies revealed a wide array of K. kingae virulence factors that facilitate oropharyngeal colonization, invasion of the bloodstream, and dissemination to skeletal tissues and the endocardium.

This Special Issue of Microorganisms aims to present a collection of articles that provide a current update of the research in the K. kingae field. Manuscripts covering all aspects of research relating to K. kingae are welcome, including the bacterium's biology and its pathogenesis, epidemiology, clinical disease, and diagnostics.

Prof. Dr. Pablo Yagupsky
Prof. Dr. Stephane Bonacorsi
Guest Editors

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Keywords

  • Kingella kingae
  • genomics
  • virulence factors
  • colonization
  • invasive infections
  • children
  • culture
  • molecular detection methods

Published Papers (8 papers)

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Editorial

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3 pages, 193 KiB  
Editorial
Kingella kingae Reveals Its Secrets
by Pablo Yagupsky
Microorganisms 2022, 10(7), 1261; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10071261 - 21 Jun 2022
Cited by 2 | Viewed by 1114
Abstract
Sixty years ago, Elizabeth O [...] Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)

Research

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13 pages, 1170 KiB  
Article
Osteoarticular Infections in Children: Accurately Distinguishing between MSSA and Kingella kingae
by Benoit Coulin, Giacomo DeMarco, Oscar Vazquez, Vasiliki Spyropoulou, Nathaly Gavira, Tanguy Vendeuvre, Anne Tabard-Fougère, Romain Dayer, Christina Steiger and Dimitri Ceroni
Microorganisms 2023, 11(1), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11010011 - 20 Dec 2022
Cited by 5 | Viewed by 1582
Abstract
Introduction: Osteoarticular infections (OAIs) constitute serious paediatric conditions that may cause severe complications. Identifying the causative organism is one of the mainstays of the care process, since its detection will confirm the diagnosis, enable adjustments to antibiotic therapy and thus optimize outcomes. Two [...] Read more.
Introduction: Osteoarticular infections (OAIs) constitute serious paediatric conditions that may cause severe complications. Identifying the causative organism is one of the mainstays of the care process, since its detection will confirm the diagnosis, enable adjustments to antibiotic therapy and thus optimize outcomes. Two bacteria account for the majority of OAIs before 16 years of age: Staphylococcus aureus is known for affecting the older child, whereas Kingella kingae affects infants and children younger than 4 years old. We aimed to better define clinical characteristic and biological criteria for prompt diagnosis and discrimination between these two OAI. Materials and methods: We retrospectively studied 335 children, gathering 100 K. kingae and 116 S. aureus bacteriologically proven OAIs. Age, gender, temperature at admission, involved bone or joint, and laboratory data including bacterial cultures were collected for analysis. Comparisons between patients with OAI due to K. kingae and those with OAI due to S. aureus were performed using the Mann–Whitney and Kruskal–Wallis tests. Six cut-off discrimination criteria (age, admission’s T°, WBC, CRP, ESR and platelet count) were defined, and their respective ability to differentiate between OAI patients due to K. kingae versus those with S. aureus was assessed by nonparametric receiver operating characteristic (ROC) curves. Results: Univariate analysis demonstrated significant differences between the two populations for age of patients, temperature at admission, CRP, ESR, WBC, and platelet count. AUC assessed by ROC curves demonstrated an exquisite ability to discriminate between the two populations for age of the patients; whereas AUC for CRP (0.79), temperature at admission (0.76), and platelet count (0.76) indicated a fair accuracy to discriminate between the two populations. Accuracy to discriminate between the two subgroups of patients was considered as poor for WBC (AUC = 0.62), and failed for ESR (AUC = 0.58). On the basis of our results, the best model to predict K. kingae OAI included of the following cut-offs for each parameter: age < 43 months, temperature at admission < 37.9 °C, CRP < 32.5 mg/L, and platelet count > 361,500/mm3. Conclusions: OAI caused by K. kingae affects primarily infants and toddlers aged less than 4 years, whereas most of the children with OAI due to MSSA were aged 4 years and more. Considering our experience on the ground, only three variables were very suggestive of an OAI caused by K. kingae, i.e., age of less than 4 years, platelet count > 400,000, and a CRP level below 32.5 mg/L, whereas WBC and ESR were relatively of limited use in clinical practice. Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)
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7 pages, 496 KiB  
Communication
Distinguishing Kingella kingae from Pyogenic Acute Septic Arthritis in Young Portuguese Children
by Catarina Gouveia, Ana Subtil, Susana Norte, Joana Arcangelo, Madalena Almeida Santos, Rita Corte-Real, Maria João Simões, Helena Canhão and Delfin Tavares
Microorganisms 2022, 10(6), 1233; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10061233 - 16 Jun 2022
Cited by 5 | Viewed by 1376
Abstract
(1) Background: We aim to identify clinical and laboratorial parameters to distinguish Kingella kingae from pyogenic septic arthritis (SA). (2) Methods: A longitudinal, observational, single-centre study of children < 5 years old with microbiological positive SA admitted to a paediatric hospital [...] Read more.
(1) Background: We aim to identify clinical and laboratorial parameters to distinguish Kingella kingae from pyogenic septic arthritis (SA). (2) Methods: A longitudinal, observational, single-centre study of children < 5 years old with microbiological positive SA admitted to a paediatric hospital from 2013–2020 was performed. Clinical and laboratorial data at admission and at 48 h, as well as on treatment and evolution, were obtained. (3) Results: We found a total of 75 children, 44 with K. kingae and 31 with pyogenic infections (mostly MSSA, S. pneumoniae and S. pyogenes). K. kingae affected younger children with low or absent fever, low inflammatory markers and a favourable prognosis. In the univariate analyses, fever, septic look, CRP and ESR at admission and CRP at 48 h were significantly lower in K. kingae SA. In the multivariate analyses, age > 6 months ≤ 2 years, apyrexy and CRP ≤ 100 mg/L were significative, with an overall predictive positive value of 86.5%, and 88.4% for K. kingae. For this model, ROC curves were capable of differentiating (AUC 0.861, 95% CI 0.767–0.955) K. kingae SA from typical pathogens. (4) Conclusions: Age > 6 months ≤ 2 years, apyrexy and PCR ≤ 100 mg/L were the main predictive factors to distinguish K. kingae from pyogenic SA < 5 years. These data need to be validated in a larger study. Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)
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Review

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7 pages, 248 KiB  
Review
Kingella kingae Virulence Factors and Insights into Pathogenicity
by Eric A. Porsch
Microorganisms 2022, 10(5), 997; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10050997 - 10 May 2022
Cited by 4 | Viewed by 1554
Abstract
The emergence of Kingella kingae as an important etiology of pediatric osteoarticular infections over the past three decades has led to significant research efforts focused on understanding the pathogenicity of this fastidious Gram-negative bacterium. This work has uncovered multiple virulence factors that likely [...] Read more.
The emergence of Kingella kingae as an important etiology of pediatric osteoarticular infections over the past three decades has led to significant research efforts focused on understanding the pathogenicity of this fastidious Gram-negative bacterium. This work has uncovered multiple virulence factors that likely play key roles in the ability of the organism to colonize the upper respiratory tract, breach the epithelial barrier, and disseminate to distal sites of infection. Herein the current body of knowledge about K. kingae virulence factors is reviewed in the context of K. kingae disease pathogenesis. The work summarized here has identified multiple targets for therapeutic intervention as well as potential vaccine antigens. Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)
16 pages, 1930 KiB  
Review
Pharyngeal Colonization by Kingella kingae, Transmission, and Pathogenesis of Invasive Infections: A Narrative Review
by Pablo Yagupsky
Microorganisms 2022, 10(3), 637; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10030637 - 17 Mar 2022
Cited by 5 | Viewed by 1796
Abstract
With the appreciation of Kingella kingae as a prime etiology of osteoarticular infections in young children, there is an increasing interest in the pathogenesis of these diseases. The medical literature on K. kingae’s colonization and carriage was thoroughly reviewed. Kingella kingae colonizes [...] Read more.
With the appreciation of Kingella kingae as a prime etiology of osteoarticular infections in young children, there is an increasing interest in the pathogenesis of these diseases. The medical literature on K. kingae’s colonization and carriage was thoroughly reviewed. Kingella kingae colonizes the oropharynx after the second life semester, and its prevalence reaches 10% between the ages of 12 and 24 months, declining thereafter as children reach immunological maturity. Kingella kingae colonization is characterized by the periodic substitution of carried organisms by new strains. Whereas some strains frequently colonize asymptomatic children but are rarely isolated from diseased individuals, others are responsible for most invasive infections worldwide, indicating enhanced virulence. The colonized oropharyngeal mucosa is the source of child-to-child transmission, and daycare attendance is associated with a high carriage rate and increased risk of invasive disease. Kingella kingae elaborates a potent repeat-in-toxin (RTXA) that lyses epithelial, phagocytic, and synovial cells. This toxin breaches the epithelial barrier, facilitating bloodstream invasion and survival and the colonization of deep body tissues. Kingella kingae colonization and carriage play a crucial role in the person-to-person transmission of the bacterium, its dissemination in the community, and the pathogenesis of invasive infections. Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)
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52 pages, 4486 KiB  
Review
Kingella kingae RtxA Cytotoxin in the Context of Other RTX Toxins
by Katerina Filipi, Waheed Ur Rahman, Adriana Osickova and Radim Osicka
Microorganisms 2022, 10(3), 518; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10030518 - 27 Feb 2022
Cited by 6 | Viewed by 2712
Abstract
The Gram-negative bacterium Kingella kingae is part of the commensal oropharyngeal flora of young children. As detection methods have improved, K. kingae has been increasingly recognized as an emerging invasive pathogen that frequently causes skeletal system infections, bacteremia, and severe forms of infective [...] Read more.
The Gram-negative bacterium Kingella kingae is part of the commensal oropharyngeal flora of young children. As detection methods have improved, K. kingae has been increasingly recognized as an emerging invasive pathogen that frequently causes skeletal system infections, bacteremia, and severe forms of infective endocarditis. K. kingae secretes an RtxA cytotoxin, which is involved in the development of clinical infection and belongs to an ever-growing family of cytolytic RTX (Repeats in ToXin) toxins secreted by Gram-negative pathogens. All RTX cytolysins share several characteristic structural features: (i) a hydrophobic pore-forming domain in the N-terminal part of the molecule; (ii) an acylated segment where the activation of the inactive protoxin to the toxin occurs by a co-expressed toxin-activating acyltransferase; (iii) a typical calcium-binding RTX domain in the C-terminal portion of the molecule with the characteristic glycine- and aspartate-rich nonapeptide repeats; and (iv) a C-proximal secretion signal recognized by the type I secretion system. RTX toxins, including RtxA from K. kingae, have been shown to act as highly efficient ‘contact weapons’ that penetrate and permeabilize host cell membranes and thus contribute to the pathogenesis of bacterial infections. RtxA was discovered relatively recently and the knowledge of its biological role remains limited. This review describes the structure and function of RtxA in the context of the most studied RTX toxins, the knowledge of which may contribute to a better understanding of the action of RtxA in the pathogenesis of K. kingae infections. Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)
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12 pages, 304 KiB  
Review
Kingella kingae Osteoarticular Infections Approached through the Prism of the Pediatric Orthopedist
by Giacomo DeMarco, Moez Chargui, Benoit Coulin, Benoit Borner, Christina Steiger, Romain Dayer and Dimitri Ceroni
Microorganisms 2022, 10(1), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010025 - 24 Dec 2021
Cited by 12 | Viewed by 2659
Abstract
Nowadays, Kingella kingae (K. kingae) is considered as the main bacterial cause of osteoarticular infections (OAI) in children aged less than 48 months. Next to classical acute hematogenous osteomyelitis and septic arthritis, invasive K. kingae infections can also give rise to [...] Read more.
Nowadays, Kingella kingae (K. kingae) is considered as the main bacterial cause of osteoarticular infections (OAI) in children aged less than 48 months. Next to classical acute hematogenous osteomyelitis and septic arthritis, invasive K. kingae infections can also give rise to atypical osteoarticular infections, such as cellulitis, pyomyositis, bursitis, or tendon sheath infections. Clinically, K. kingae OAI are usually characterized by a mild clinical presentation and by a modest biologic inflammatory response to infection. Most of the time, children with skeletal system infections due to K. kingae would not require invasive surgical procedures, except maybe for excluding pyogenic germs’ implication. In addition, K. kingae’s OAI respond well even to short antibiotics treatments, and, therefore, the management of these infections requires only short hospitalization, and most of the patients can then be treated safely as outpatients. Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)

Other

9 pages, 457 KiB  
Perspective
Kingella kingae and Viral Infections
by Romain Basmaci, Philippe Bidet and Stéphane Bonacorsi
Microorganisms 2022, 10(2), 230; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10020230 - 21 Jan 2022
Cited by 3 | Viewed by 1538
Abstract
Kingella kingae (K. kingae) is an oropharyngeal commensal agent of toddlers and the primary cause of osteoarticular infections in 6–23-month-old children. Knowing that the oropharynx of young children is the reservoir and the portal of entry of K. kingae, these [...] Read more.
Kingella kingae (K. kingae) is an oropharyngeal commensal agent of toddlers and the primary cause of osteoarticular infections in 6–23-month-old children. Knowing that the oropharynx of young children is the reservoir and the portal of entry of K. kingae, these results suggested that a viral infection may promote K. kingae infection. In this narrative review, we report the current knowledge of the concomitance between K. kingae and viral infections. This hypothesis was first suggested because some authors described that symptoms of viral infections were frequently concomitant with K. kingae infection. Second, specific viral syndromes, such as hand, foot and mouth disease or stomatitis, have been described in children experiencing a K. kingae infection. Moreover, some clusters of K. kingae infection occurring in daycare centers were preceded by viral outbreaks. Third, the major viruses identified in patients during K. kingae infection were human rhinovirus or coxsackievirus, which both belong to the Picornaviridae family and are known to facilitate bacterial infections. Finally, a temporal association was observed between human rhinovirus circulation and K. kingae infection. Although highly probable, the role of viral infection in the K. kingae pathophysiology remains unclear and is based on case description or temporal association. Molecular studies are needed. Full article
(This article belongs to the Special Issue Kingella kingae: Virulence Factors, Clinical Disease, and Diagnostics)
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