Interactions of the emerging fungus
Candida auris
with
Acanthamoeba castellanii
reveal phenotypic changes with direct implications on the response to stress and virulence
Authors: Valente Michele Ramos , Martins Alcântara Lucas , Cintra Deborah Santos , Mendoza Susana Ruiz , Medeiros Elisa Gonçalves , Gomes Kamilla Xavier , Honorato Leandro , Almeida Marcos de Abreu , Vieira Carmen Baur , Nosanchuk Joshua Daniel , Sgarbi Diana Bridon da Graça , Pinto Marcia Ribeiro , Nimrichter Leonardo , Guimarães Allan Jefferson 
Published: December 2024

Candida auris
is an emerging fungal pathogen notable for its resistance to multiple antifungals and ability to survive in various environments. Understanding the interactions between
C. auris
and environmental protozoa, such as
Acanthamoeba castellanii,
could provide insights into fungal adaptability and pathogenicity. Two
C. auris
isolates (MMC1 and MMC2) were co-cultured with
A. castellanii
to examine interaction dynamics, survival, stress responses, growth, virulence, biofilm formation, and antifungal susceptibility. The association
of C. auris-A. castellanii
varied with a multiplicity of infection (MOI), with MMC2 exhibiting higher association rates at increased MOI than MMC1. Both isolates survived distinctly within
A. castellanii
, as the MMC1 showed an initial decline and subsequent increase in viability, while MMC2 maintained higher viability for up to 24 h, decreasing afterward. Both isolates exhibited accelerated growth when recovered from
A. castellanii
. The MMC2 isolate displayed increased resistance to oxidative, osmotic, and thermal stresses upon interaction with
A. castellanii
, whereas MMC1 showed limited changes. Exposure to
A. castellanii
also influenced the expression of virulence factors differently, with MMC1 increasing phospholipase and peptidase, while MMC2 upregulated phytase, esterase, hemolysin, and siderophores. Upon contact with
A. castellanii
, MMC2 enhanced biofilm formation, unlike MMC1. Both isolates increased ergosterol upon interactions, enhancing susceptibility to amphotericin B. However, both isolates were more tolerant to itraconazole and caspofungin, particularly MMC2, which showed differential expression of ergosterol biosynthesis enzymes and increased cell wall polysaccharides. This study reveals that interactions with
A. castellanii
modulate
C. auris
physiology and virulence, contributing to its environmental adaptability and resistance to antifungals.

IMPORTANCE

Candida auris
has emerged as a critical public health concern due to its resistance to multiple antifungal drugs and ability to survive on surfaces under harsh conditions, mainly due to biofilm formation. The precise origin of this emerging pathogen still awaits elucidation, but interactions with environmental protozoa may have helped
C. auris
to develop such virulence and resistance traits. In this work, we precisely characterize the interactions of
C. auris
with the free-living amoeba
Acanthamoeba castellanii
and how these protozoa may alter the fungal behavior in terms of virulence, thermotolerance, biofilm formation capacity, and drug resistance. It may be essential to understand the various interactions
C. auris
could perform in the environment, directly impacting the outcome of human infections under the One Health approach.