Investigating Antifungal Susceptibility in Candida Species With MALDI-TOF MS-Based Assays.

Margot Delavy,Andrea R Dos Santos,Clara M Heiman,Alix T Coste

doi:10.3389/fcimb.2019.00019

Abstract

Half of invasive fungal infections lead to death. Amongst pathogenic fungi, the most widespread species belong to the Candida genus and vary in their susceptibility to antifungal drugs. The emergence of antifungal resistance has become a major clinical problem. Therefore, the definition of susceptibility patterns is crucial for the survival of patients and the monitoring of resistance epidemiology. Although, most routinely used methods of AntiFungal Susceptibility Testing (AFST) have reached their limits, the rediscovery of Matrix Associated Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) in the field of mycology provides a promising alternative for the study of antifungal resistance. MALDI-TOF MS is already used in mycology for fungal identification, which permits to highlight inherent antifungal resistance. However, the main concern of clinicians is the rise of acquired antifungal resistance and the time needed for their detection. For this purpose, MALDI-TOF MS has been shown to be an accurate tool for AFST, presenting numerous advantages in comparison to commonly used techniques. Finally, MALDI-TOF MS could be used directly to detect resistance mechanisms through typing. Consequently, MALDI-TOF MS offers new perspectives in the context of healthcare associated outbreaks of emerging multi-drug resistant fungi, such as C. auris. As a proof of concept, we will illustrate the current and future benefits in using and adapting MALDI-TOF MS-based assays to define the susceptibility pattern of C. auris, by species identification, AFST, and typing.

Highlights

Fungal infections range from harmless superficial infections to invasive illnesses causing generalized sepsis and often leading to death (Brown et al, 2012)
In 2009, Marinach et al developed a first MALDI-TOF MSbased assay to discriminate fluconazole-resistant C. albicans strains from susceptible ones
Their method is based on the determination of the minimal profile change concentration (MPCC) for a given strain, a new alternative endpoint to the classical minimum inhibitory concentration (MIC)

Summary

INTRODUCTION

Fungal infections range from harmless superficial infections to invasive illnesses causing generalized sepsis and often leading to death (Brown et al, 2012). Invasive fungal infections are of great concern for clinicians because of the high mortality rate, which reaches up to 50% of patients (Brown et al, 2012). Most of these infections are caused by opportunistic pathogens that take advantage of immunosuppression (HIV/AIDS or cancer patients), even though they are commensal in healthy individuals (Brown et al, 2012). We will illustrate how Matrix Associated Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) could be a promising alternative to the routine methods

Treatment of Fungal Infections and Emergence of Antifungal Resistance

Findings

Current Routine AFST Methods