Investigating the impact of polymicrobial interactions on fungal pathogenicity

Within the human body, microorganisms reside as part of a complex and varied ecosystem, where they rarely exist in isolation. Bacteria and fungi have co-evolved to develop elaborate and intricate relationships, utilising both physical and chemical communication mechanisms. Mucorales are filamentous fungi that are the causative agents of mucormycosis in immunocompromised individuals. Key to the pathogenesis is the ability to germinate and penetrate the surrounding tissues, leading to angioinvasion, vessel thrombosis, and tissue necrosis. It is currently unknown whether Mucorales participate in polymicrobial relationships, and if so, how this affects the pathogenesis. This project analyses the relationship between Mucorales and the microorganisms they may encounter. Here we show that Pseudomonas aeruginosa culture supernatants and live bacteria inhibit Rhizopus microsporus germination through the sequestration of iron. Therefore, treatment of P. aeruginosa in a patient could result in the release of this inhibition, leaving the patient more susceptible to an underlying fungal infection. However, P. aeruginosa responds to the presence of R. microsporus by enhancing siderophore production, which increases host mortality in a zebrafish co-infection model. This project highlights the complex competition between these organisms and the possible enhanced disease pathology when R. microsporus and P. aeruginosa meet in a host

Pseudomonas aeruginosa inhibits Rhizopus microsporus germination through sequestration of free environmental iron

Rhizopus spp are the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infection. Key to pathogenesis is the ability of fungal spores to swell, germinate, and penetrate surrounding tissues. Antibiotic treatment in at-risk patients increases the probability of the patient developing mucormycosis, suggesting that bacteria have the potential to control the growth of the fungus. However, research into polymicrobial relationships involving Rhizopus spp has not been extensively explored. Here we show that co-culturing Rhizopus microsporus and Pseudomonas aeruginosa results in the inhibition of spore germination. This inhibition was mediated via the secretion of bacterial siderophores, which induced iron stress on the fungus. Addition of P. aeruginosa siderophores to R. microsporus spores in the zebrafish larval model of infection resulted in inhibition of fungal germination and reduced host mortality. Therefore, during infection antibacterial treatment may relieve bacterial imposed nutrient restriction resulting in secondary fungal infections