Cooperative Evolutionary Strategy between the Bacteriome and Mycobiome

Abstract

Nonhealing chronic wounds are all unique in origin and circumstance, and attempting to isolate a single etiology for the failure of a wound to heal is daunting. Wounds represent complex systems of multispecies fungal and bacterial biofilms. The survival strategies of interactive microbial communities have led to cooperative evolutionary strategies that culminate in biofilm formation. In microbial dysbiosis, biofilms are beneficial to both bacterial and fungal communities but detrimental to the host. Fungi benefit by a surge in their virulence factors, while bacteria become tolerant to antibacterials as a consequence of living under the protective umbrella of the biofilm matrix. This interkingdom cooperation negatively impacts the host, as the fungi and bacteria produce extracellular enzymes that inflict tissue damage, leading to an increase in proinflammatory cytokines, which results in oxidative damage and apoptotic cell death.

FIG 1

Interkingdom cooperation between fungi and bacteria. Chronic wounds are complex systems of multispecies fungal and bacterial biofilms. These biofilms provide a protected milieu for microbes living in close proximity. Fungal cells form the biofilm core while bacteria associate around the periphery of the cells. The fungal hyphae and microbial-secreted enzymes/metabolites facilitate invasion of the skin epidermis/dermis leading to host tissue damage and inflammatory response manifested by an increase in proinflammatory cytokine production (panel A). Panel B shows disruption of the biofilm matrix by zymolase thereby unmasking the microbes. Consequently, treatment with antifungal agents (e.g., echinocandins) and antibiotics leads to microbial cell death (gray/black color) and a decrease in the production of proinflammatory cytokines. IFN-γ, gamma interferon; TNF-α, tumor necrosis factor alpha; IL-6, -17, and -23, interleukins 6, 17, and 23, respectively.