Structural and functional coordination of minor pilins and pilc adhesins governs type iv pilus activity in the pediatric pathogen <em>kingella kingae</em> Taylor Yount

Format:

Book

Thesis/Dissertation

Author/Creator:

Yount, Taylor, author.

Contributor:

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

Language:

English

Subjects (All):

Microbiology.

Biology.

Biochemistry.

Pediatrics.

0410.

0487.

0767.

0306.

Local Subjects:

Microbiology.

Biology.

Biochemistry.

Pediatrics.

0410.

0487.

0767.

0306.

Genre:

Academic theses

Physical Description:

1 online resource (177 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

Kingella kingae is an emerging pediatric pathogen and a leading cause of osteoarticular infections in young children. K. kingae relies on proteinaceous surface fibers called type IV pili (T4P) to initiate colonization of the oropharyngeal epithelium, the first step in the pathogenesis of disease. T4P are important virulence factors that mediate adherence, twitching motility, and DNA uptake, and are produced by many bacterial pathogens, including Neisseria spp., Vibrio cholerae, and Pseudomonas aeruginosa, among others. K. kingae T4P consist of many monomeric proteins called pilins and two large pilus-associated proteins called PilC1 and PilC2, which belong to the PilC/PilY family of adhesins. This dissertation investigates how major pilin molecules, minor pilins, and the PilC proteins coordinate pilus assembly and function to promote interaction with host tissues and virulence. Using a combination of bacterial genetics, biochemical assays, functional assays, and in silico structural modeling, this work dissects the roles of core and non- core minor pilins, elucidates the interactions of minor pilins with the PilC adhesins, and maps functional domains of the PilC proteins required for pilus-mediated phenotypes. The results demonstrated that five core minor pilins (FimT, PilV, PilW, PilX, and PilE) form a multi-protein complex essential for T4P-dependent adherence, twitching motility, and natural transformation, suggesting that they provide a conserved scaffold for PilC family protein incorporation into the pilus fiber. Structural modeling and site-directed mutagenesis established that conserved C-terminal tails of both PilC1 and PilC2 bind to PilX within the core minor pilin complex through -strand augmentation, an anchoring mechanism that appears to be conserved across PilC/PilY family proteins in T4P-expressing organisms. Furthermore, the adhesive activity of PilC1 and PilC2 localizes to their N-terminal domains, which bind to a variety of different cell types and likely mediate the broad tissue tropism observed for K. kingae. Together, these findings establish a model where a conserved C-terminal anchoring mechanism attaches PilC/PilY adhesins to the pilus fiber via the core minor pilin complex, enabling stabilization of T4P architecture and promoting function. This work advances our understanding of T4P-mediated virulence and identifies conserved protein-protein interfaces that may represent targets for anti-adhesion therapeutics against T4P-expressing pathogens.

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Brodsky, Igor E.; Geme, Joseph W. St., III Committee members: Pohlschröder, Mecky; Zhu, Jun Jay; Zackular, Joseph P.

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247972730

Access Restriction:

Restricted for use by site license