Micafungin-Induced Cell Wall Damage Stimulates Morphological Changes Consistent with Microcycle Conidiation in Aspergillus nidulans.

Samantha Reese,Cynthia Chelius,Wayne Riekhof,Mark R Marten,Steven D Harris

doi:10.3390/jof7070525

Abstract

Fungal cell wall receptors relay messages about the state of the cell wall to the nucleus through the Cell Wall Integrity Signaling (CWIS) pathway. The ultimate role of the CWIS pathway is to coordinate repair of cell wall damage and to restore normal hyphal growth. Echinocandins such as micafungin represent a class of antifungals that trigger cell wall damage by affecting synthesis of β-glucans. To obtain a better understanding of the dynamics of the CWIS response and its multiple effects, we have coupled dynamic transcriptome analysis with morphological studies of Aspergillus nidulans hyphae in responds to micafungin. Our results reveal that expression of the master regulator of asexual development, BrlA, is induced by micafungin exposure. Further study showed that micafungin elicits morphological changes consistent with microcycle conidiation and that this effect is abolished in the absence of MpkA. Our results suggest that microcycle conidiation may be a general response to cell wall perturbation which in some cases would enable fungi to tolerate or survive otherwise lethal damage.

Highlights

The cell wall is an important feature of filamentous fungi, where it is responsible for the protection of hyphal integrity and the maintenance of hyphal morphology [1]
Our results suggest that the response to cell wall damage is attenuated in ∆mpkA mutants and reveal specific classes of genes whose expression is dependent upon MpkA
We show that morphological changes consistent with microcycle conidiation are triggered by exposure to micafungin, thereby raising the possibility that microcycle conidiation might be a critical feature of the response to anti-fungal drugs

Summary

Introduction

The cell wall is an important feature of filamentous fungi, where it is responsible for the protection of hyphal integrity and the maintenance of hyphal morphology [1]. Damage to the cell wall poses a serious threat to cell viability To mitigate this possibility, fungi employ cell surface sensors that detect damage to the cell wall and activate a suite of mechanisms that repair the damage and enable the resumption of normal growth [1]. Fungi employ cell surface sensors that detect damage to the cell wall and activate a suite of mechanisms that repair the damage and enable the resumption of normal growth [1] This response is known as the Cell Wall Integrity Signaling (CWIS) pathway [2]. This pathway is found in many fungal species and key signaling features includes the Rho. In Aspergillus nidulans, the pathway is conserved and terminates with the MAP kinase MpkA [3]

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