Investigating the factors determining Aspergillus fumigatus virulence and the variations of virulence between clinical isolates

Abstract

Aspergillus fumigatus is a leading cause of mortality in immunocompromised patients. The most common cause of death from A. fumigatus is Invasive Aspergillosis (IA), which starts off as a respiratory disease. IA prevalence has been rising in recent years because of the advent of organ and bone marrow transplantation, which requires immunosuppressive drugs. Previous studies on A. fumigatus virulence have so far failed to ascertain the factors in determining the differences in virulence levels between isolates. It is also unknown why some strains only cause colonising infection, while other strains cause invasive infection. To determine the factors affecting the virulence levels of A. fumigatus, and the causes thereof, 15 clinical isolates were obtained from Westmead Hospital, of which 10 were colonising and 5 were invasive. A variety of phenotypic tests were carried out, such as conidial size measurements, resistance to Reactive Oxygen Species (ROS) acute exposure, proteolysis and urea hydrolysis. These were compared to virulence results, obtained through mortality counts in the insect model Tenebrio molitor. Results indicated that conidial sizes and proteolysis seemed to have little effect on virulence. Also, the most virulent strains appeared to be the colonising isolates. While resistance to ROS acute exposure was lower in invasive isolates, this mirrors previous findings that toxigenic A. fumigatus strains are more affected by ROS exposure, inducing the secretion of toxins, including those responsible for tissue and bloodstream invasion. Urea hydrolysis was also found to be higher in invasive isolates, indicating an improved ability to survive in acidic lung mucosa, and an ability to encourage adaptive immune responses which overlook fungal infections. The results of this study contribute to the increasing knowledge of factors affecting A. fumigatus virulence.

Date of Award	2018
Original language	English