Virulence Properties of Kingella kingae That Facilitate Evasion of Host Immunity Kevin Antonio Hernandez

Format:

Book

Thesis/Dissertation

Author/Creator:

Hernandez, Kevin Antonio, author.

Contributor:

University of Pennsylvania. Cell and Molecular Biology., degree granting institution.

Language:

English

Subjects (All):

Microbiology.

Cellular biology.

Immunology.

0410.

0379.

0982.

Local Subjects:

Microbiology.

Cellular biology.

Immunology.

0410.

0379.

0982.

Physical Description:

1 electronic resource (133 pages)

Contained In:

Dissertations Abstracts International 86-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2025

Language Note:

English

Summary:

Kingella kingae is a gram-negative bacterium that has emerged as a leading cause of invasive disease in children aged between 6 months and 4 years. K. kingae initiates infection by colonizing the oropharynx and then breaches the oropharyngeal epithelium, enters the bloodstream, and disseminates to distant sites, causing osteomyelitis, septic arthritis, and endocarditis. To survive in the bloodstream and disseminate, K. kingae must overcome innate immune mechanisms.Earlier work established that the K. kingae capsule and exopolysaccharide promote resistance to complement-mediated serum resistance. However, eliminating these polysaccharides only partially reduces K. kingae survival in human serum, suggesting other factors contribute to serum resistance. Using flow cytometry, we found that K. kingae binds human factor H (fH), a negative regulator of the alternative complement pathway. Binding of human fH was associated with resistance to rat complement-mediated killing and enhanced virulence in the juvenile rat model of K. kingae disease, demonstrating the importance of fH binding in K. kingae pathogenesis. We discovered that the outer membrane protein, KK02920, is essential for fH binding, serum resistance, and enhanced virulence in juvenile rats.The K. kingae population contains four capsule types (types a, b, c, and d), with type a and type b accounting for over 95% of invasive disease isolates. However, it is unknown whether capsule type dictates virulence. Using isogenic derivatives of K. kingae, we found that capsule type is a major determinant of virulence in infant rats, with capsule type a and type b contributing to greater virulence compared to capsule type c and type d. Additional work revealed that antibodies generated against specific capsule types were protective against K. kingae invasive disease in juvenile rats.This work demonstrates the importance of a complement-regulator binding protein as a major mechanism of serum resistance in an encapsulated organism, highlights that K. kingae capsule type is a major determinant of virulence, and suggests that the K. kingae capsule may serve as an effective vaccine antigen to protect against K. kingae invasive disease

Notes:

Source: Dissertations Abstracts International, Volume: 86-12, Section: B.

Advisors: St. Geme, Joseph W., III Committee members: Shin, Sunny; Zhu, Jun Jay; Silverman, Michael A.; Zackular, Joseph P.

Ph.D. University of Pennsylvania 2025

Local Notes:

School code: 0175

ISBN:

9798280759497

Access Restriction:

Restricted for use by site license