Evaluating the contribution of a metal independent aldolase to resisting nutritional immunity

The sequestration of essential nutrients from pathogens is a key component in the vertebrate immune response. One aspect of this defense, known as nutritional immunity, is the sequestration of the essential metals manganese and zinc. An important component of this defense is the metal binding host protein calprotectin, which inactivates metal- dependent bacterial enzymes. The ability of Staphylococcus aureus to cause infection suggests that it has mechanisms that enable it to minimize the impact of nutrient metal limitation. The consumption of glucose is critical to the ability of S. aureus to overcome nitrosative stress. Yet at the same time several of the primary glycolytic enzymes utilized by S. aureus are predicted to be dependent on a metal for function, including a putatively zinc-dependent aldolase. S. aureus possesses an additional metal-independent aldolase, which is regulated by the two-component regulator ArlRS. This two-component system has previously been linked to the ability of S. aureus to resist calprotectin-imposed metal limitation. In light of these observations, we evaluated if the metal-independent aldolase contributes to the ability of S. aureus grow in metal restricted environments. These data show that when the metal-independent aldolase is impaired, S. aureus shows greater sensitivity to metal limitation. This is alleviated upon addition of manganese, but not zinc. Increasing manganese limitation by ablating manganese transport exacerbates the phenotype of the aldolase mutant. In addition, the availability of an alternative carbon source can reduce calprotectin sensitivity, provided its entry point in glycolysis is below the metal-dependent blockage. This suggests that a blockage at the aldolase step in glycolysis is important for S. aureus to resolve, either through the use of a metal-independent isozyme or other carbon sources, in order to resist calprotectin-induced metal limitation.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Bastille, Talina S.

Contributors dc:contributor

• Kehl-Fie, Thomas
• Slauch, James
• Metcalf, William

• staphylococcus aureus, nutritional immunity

Statement dc:rights

• Copyright 2019 Talina Bastille

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/106407

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/106407