Pathogenic determinants of Kingella kingae disease

Abstract

Kingella kingae is an emerging pediatric pathogen and is increasingly recognized as a leading etiology of septic arthritis, osteomyelitis, and bacteremia and an occasional cause of endocarditis in young children. The pathogenesis of K. kingae disease begins with colonization of the upper respiratory tract followed by breach of the respiratory epithelial barrier and hematogenous spread to distant sites of infection, primarily the joints, bones, and endocardium. As recognition of K. kingae as a pathogen has increased, interest in defining the molecular determinants of K. kingae pathogenicity has grown. This effort has identified numerous bacterial surface factors that likely play key roles in the pathogenic process of K. kingae disease, including type IV pili and the Knh trimeric autotransporter (adherence to the host), a potent RTX-family toxin (epithelial barrier breach), and multiple surface polysaccharides (complement and neutrophil resistance). Herein, we review the current state of knowledge of each of these factors, providing insights into potential approaches to the prevention and/or treatment of K. kingae disease.

Acquisition, co-option, and duplication of thertxtoxin system and the emergence of virulence inKingella

“…K. kingae isolates contain either one or two copies of rtxCrtxAtolC . 7,10,13 To date, little is known about the genomics of K. negevensis due to both a lack of available isolates and a lack of whole genome sequencing. 41 To determine how many RTX loci are present in K. negevensis , we performed Oxford Nanopore Technologies (ONT) MinION sequencing on a collection of 12 isolates (Table S1).…”

“…1,2 Recent studies have identified five major virulence determinants that are conserved across this species: type IV pili, a trimeric autotransporter adhesin called Knh, a polysaccharide capsule, an exopolysaccharide, and a broadly active RTX cytotoxin called RtxA. 7 The lipopolysaccharide-associated exopolysaccharide and the RtxA toxin are found only in pathogenic Kingella species. 11,47 In this study, we reconstructed the evolutionary history of rtxA in the pathogenic Kingella species based on a large collection of isolates from both invasive disease and oropharyngeal carriage.…”

“…6 The development of invasive disease by K. kingae is facilitated by several virulence factors, including an RTX family toxin, type IV pili, an autotransporter adhesin, a lipopolysaccharide-associated exopolysaccharide, and a polysaccharide capsule. 7 Together, these factors are thought to allow K. kingae to adhere to and lyse host cells, resist complement-mediated killing and neutrophil phagocytosis in the bloodstream, and subvert neutrophil killing at the site of disease. Of the five species that comprise the Kingella genus, only K. kingae and K. negevensis have been repeatedly associated with invasive disease in immunocompetent individuals.…”

“…10 In at least one strain (KWG-1), there are two copies of both rtxA and tolC , with the second copy of these genes downstream of rtxB and rtxD . 7,10,13 The impact of this duplication on virulence and pathogenicity is unknown.…”

Infective Endocarditis Due to Kingella kingae

“…Afterward, a breach in the epithelial barrier is required to allow the organism to enter the bloodstream where dissemination to distant sites can take place. Several pathogenic characteristics of K. kingae such as pili, exotoxin, polysaccharide capsule, and galactan exopolysaccharide seem to be essential for the bacteria to survive in the intravascular compartment as well as in various body sites such as endocardium [ 21 ], and these are detailed hereafter.…”