Online Archive of University of Virginia Scholarship
Zinc (II) Capture and Tolerance in Neisseria Gonorrhoeae13 views
Author
Liyayi, Ian, Microbiology - School of Medicine, University of Virginia0000-0002-1713-123X
Advisors
Criss, Alison, MD-MICR Microbiology, University of Virginia
Abstract
Zinc (II) (Zn) is an essential cofactor required by nearly half of all enzymes in both human and bacterial proteomes. During infection, mammalian hosts restrict Zn availability by inducing metal import and deploying metal sequestering proteins in a process termed nutritional immunity. Neisseria gonorrhoeae (Gc) subverts host-imposed zinc restriction by producing outer membrane transporters that pirate Zn from the human Zn-sequestering proteins calprotectin and psoriasin. While the transcriptome of Zn-limited Gc has been defined, many gene products that enable survival in Zn-limited niches remain uncharacterized. In this thesis, I characterized ngo1049, which encodes a DUF4198 family protein subsequently named Zcp (Zn capture protein). Zcp is a Zn-binding periplasmic homodimer that is highly produced in Zn-limited Gc. Zcp enhances the growth and infectivity of Gc during zinc restriction. In the periplasm, Zcp interacts with extracytoplasmic clients and promotes envelope integrity. This work defines DUF4198 proteins as metal-buffering substrate-binding proteins that help subvert host-imposed nutritional immunity. Because the host exploits also Zn toxicity to curb bacterial survival, I interrogated how Gc contends with Zn intoxication. Gc tolerates submillimolar Zn concentrations, and this level varies among strains, suggesting diversity in metal detoxification systems. Deletion of the copper efflux protein CopA or the manganese efflux protein MntX altered Zn tolerance, indicating complexities of metal homeostasis in Gc that remain to be fully uncovered. Together, this work provides new knowledge into mechanisms of metal homeostasis and identifies targets for future investigation. Understanding how pathogens maintain metal homeostasis within the host could uncover new antimicrobial targets and guide vaccine development.
Liyayi, Ian. Zinc (II) Capture and Tolerance in Neisseria Gonorrhoeae. University of Virginia, Microbiology - School of Medicine, PHD (Doctor of Philosophy), 2026-02-11, https://doi.org/10.18130/was7-dg73.
