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

Abstract

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.

Effect of quorum sensing and quenching molecules on inter-kingdom biofilm formation by Penicillium expansum and bacteria

“…These results emphasize the protection and biotic support that the fungal hyphae confer towards this bacterium. Analysing the effect of A. calcoaceticus on P. expansum biofilm formation, an inhibition was detected towards the fungus, especially at 24 and 48 h. Similar results were observed in other studies where bacteria inhibited fungal spore germination and hyphal growth (Mowat et al 2010;Afonso et al 2019;Kousser et al 2019;Nogueira et al 2019). With the removal of planktonic cells and the renewal of the medium, viability and fungal growth increased over time as seen by the increase in biofilm mass.…”

Isolated Cerebral Mucormycosis in Immunocompetent Adults who Inject Drugs: Case Reports and Systematic Review of the Literature

“…This predilection for the basal ganglia has been hypothesized to be due to the high iron content of this tissue, as germination of Rhizopus spp. spores requires free iron [ 50 , 56 ]. Brain abscesses due to Listeria monocytogenes , another organism that requires iron for virulence, are also commonly found in the basal ganglia [ 57 , 58 ].…”

Tornadic shear stress induces a transient, calcineurin-dependent hyper-virulent phenotype in Mucorales molds

“…Cross-kingdom interactions of pathogens have been increasingly recognized as key virulence determinants shaping the outcomes of life-threatening infectious diseases (54–55). Direct physical interaction, inter-kingdom signaling, altered immunopathology, and competition for nutrients or trace elements are considered to play a driving role in the mutual modulation of bacterial and fungal virulence (54, 56). Interestingly, preliminary results of R. arrhizus and Staphylococcus aureus co-infection studies in our fruit fly model suggest that TSC-induced hyper-virulence rather increases in a mixed infection setting (Wurster et al, unpublished data), highlighting a need to obtain a more refined understanding of the influence of shear forces on the complex inter-dependencies in polymicrobial infections.…”