Exploring the role of bacterial endosymbionts in modulation of innate immune responses during infection by Rhizopus microsporus.

Itabangi, Herbert (2019). Exploring the role of bacterial endosymbionts in modulation of innate immune responses during infection by Rhizopus microsporus. University of Birmingham. Ph.D.

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Abstract

Mucormycosis is a life-threatening mold infection with overall mortality rates of 50%, yet fatality levels reach 100% in patients with disseminated disease, prolonged neutropenia, or brain involvement. The disease is caused by a group of filamentous fungi, the mucorales and particularly targets patients with immunosuppression due to diabetic ketoacidosis (DKA), iron overload, severe trauma, neutropenia, corticosteroid treatment, or organ transplantation.

These predisposing conditions are linked to defects in key aspects of the innate immunity, particularly defects in phagocytic effector functions by macrophages and neutrophils, suggesting phagocytic activity is crucial to disease control. Yet, we currently have a very limited understanding of the interaction between mucormycete infecting spores and phagocytes.

In this thesis, we show that the early events during phagocyte- spore interaction may determine infection by R. microsporus. We report that spore metabolism modulates macrophage effector functions including phagocytic uptake of spores, phagosome acidification following uptake and cytoskeletal organisation via a secreted factor.

We also demonstrate the secreted factor is not produced by R. microsporus but a bacterial endosymbiont Ralstonia pickettii. This is a close relative of Paraburkholderia species belonging to the family Bukholderiaceace that produce rhizo-toxins already characterised and implicated in plant pathology but not yet in human disease. However, although the secreted compound here shares chemical and functional attributes with the rhizo-toxins, it is not a rhizo-toxin.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):