Kingella kingae Virulence Factors and Insights into Pathogenicity

Porsch, Eric A.

doi:10.3390/microorganisms10050997

Microorganisms

2022

DOI: 10.3390/microorganisms10050997

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Kingella kingae Virulence Factors and Insights into Pathogenicity

Eric A. Porsch

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 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… Show more

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Cited by 3 publications

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“…Advances in the culture methods and especially the increasing use of molecular detection methods have resulted in recognition of the bacterium as the prime etiology of hematogenous septic arthritis, osteomyelitis, spondylodiscitis, and tenosynovitis in children aged 6–48 months ( 8 ). Intensive research conducted over the last two decades has identified a wide range of bacterial surface factors that play crucial roles in the transition from the colonized oropharyngeal surfaces to the invasion of the skeletal system tissues ( 20 ).…”

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Editorial: An update on pediatric skeletal system infections

Yagupsky

Ceroni²

2023

Front. Pediatr.

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Editorial on the Research Topic An Update on Pediatric Skeletal System InfectionsOsteoarticular infections (OAIs) in pediatric patients are medical emergencies that require early diagnosis and adequate treatment to avoid severe septic complications, prolonged morbidity, and long-term functional disability (1). Although traumatic inoculation of bacteria into the joint space and bones or dissemination from a contiguous soft tissue focus may occur, in most cases, pathogens reach the skeletal tissues through the hematogenous route (2). Because the incidence of bacteremia is elevated in immunologically naïve young children, the incidence of septic arthritis and osteomyelitis is higher in early childhood (1).Early diagnosis of skeletal infections, identification of their etiologic agent, and prompt administration of adequate antimicrobial therapy are cornerstones of managing the disease, avoiding clinical deterioration, and preventing permanent orthopedic sequelae (3). Traditionally, culture isolation of the etiologic agent, its identification, and determination of its antibiotic susceptibility was performed by conventional methods. However, causative organisms may be present in the specimen at low concentrations, difficult to isolate, and/or children may have been empirically administered antibiotics before cultures were obtained. Consequently, many pediatric joint and bone infections remained bacteriologically unconfirmed (4). Because the microbiology laboratory results are obtained with a 2-3-day delay and the danger of administering an inappropriate or poorly efficient antibiotic, the initial therapy of bone and joint infections usually consists of wide-spectrum antimicrobial drugs, including those that provide appropriate coverage of Staphylococcus aureus (3). To ensure therapeutic success, antibiotics are administered through the intravenous route in the early phase and switched to oral therapy after body temperature has normalized for 24 h, local findings and motion have improved, and C-reactive protein (CRP) levels have decreased (1).Technological progress has revolutionized the epidemiology, diagnosis, and management of pediatric OAI in recent decades, as summarized in Table 1.The present Special Issue provides an update on managing these skeletal system infections in children and the areas of controversy and current research to improve the diagnosis, shorten the duration of intravenous therapy, and reduce hospitalization length.The article by Porsch et al. summarizes our current knowledge of the virulence factors of Kingella kingae. Advances in the culture methods and especially the increasing use of molecular detection methods have resulted in recognition of the bacterium as the prime etiology of hematogenous septic arthritis, osteomyelitis, spondylodiscitis, and tenosynovitis in children aged 6-48 months (8). Intensive research conducted over the last two decades has

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Editorial: An update on pediatric skeletal system infections

Yagupsky

Ceroni²

2023

Front. Pediatr.

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“…This Special Issue, “ Kingella kingae : Virulence Factors, Clinical Disease, and Diagnostics”, gathers five papers by an international group of renowned researchers who provide a timely update on this intriguing human pathogen and its diseases. The review article by Porsch [ 17 ] summarizes our current knowledge on the wide array of K. kingae ’s constituents, which similar to other pathogens of respiratory origin, are responsible for the adherence of the bacterium to the oropharyngeal epithelium. Additional virulence factors facilitate bloodstream invasion and seeding to remote sites and ensure the survival of the organism in the skeletal system and endocardial tissues.…”

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Kingella kingae Reveals Its Secrets

Yagupsky

2022

Microorganisms

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Chimeric vaccine design against the conserved TonB-dependent receptor-like β-barrel domain from the outer membrane tbpA and hpuB proteins of Kingella kingae ATCC 23330

Mashraqi,

Alzamami,

Alturki

et al. 2023

Front. Mol. Biosci.

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Kingella kingae is a Gram-negative bacterium that primarily causes pediatric infections such as septicemia, endocarditis, and osteoarticular infections. Its virulence is attributed to the outer membrane proteins having implications in bacterial adhesion, invasion, nutrition, and host tissue damage. TonB-dependent receptors (TBDRs) play an important role in nutrition and were previously implicated as vaccine targets in other bacteria. Therefore, we targeted the conserved β-barrel TBDR domain of these proteins for designing a vaccine construct that could elicit humoral and cellular immune responses. We used bioinformatic tools to mine TBDR-containing proteins from K. kingae ATCC 23330 and then predict B- and T-cell epitopes from their conserved β-barrel TDR domain. A chimeric vaccine construct was designed using three antigenic epitopes, covering >98% of the world population and capable of inciting humoral and adaptive immune responses. The final construct elicited a robust immune response. Docking and dynamics simulation showed good binding affinity of the vaccine construct to various receptors of the immune system. Additionally, the vaccine was predicted to be safe and non-allergenic, making it a promising candidate for further development. In conclusion, our study demonstrates the potential of immunoinformatics approaches in designing chimeric vaccines against K. kingae infections. The chimeric vaccine we designed can serve as a blueprint for future experimental studies to develop an effective vaccine against this pathogen, which can serve as a potential strategy to prevent K. kingae infections.

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Kingella kingae Virulence Factors and Insights into Pathogenicity

Cited by 3 publications

References 32 publications

Editorial: An update on pediatric skeletal system infections

Editorial: An update on pediatric skeletal system infections

Kingella kingae Reveals Its Secrets

Chimeric vaccine design against the conserved TonB-dependent receptor-like β-barrel domain from the outer membrane tbpA and hpuB proteins of Kingella kingae ATCC 23330

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