Serial Systemic Candida albicans Infection Highlighted by Proteomics.

Glaucia Sayuri Arita,Eduardo Jorge Pilau,Terezinha Inez Estivalet Svidzinski,Karina Mayumi Sakita,Daniella Renata Faria,Paula Aline Zanetti Campanerut-Sá,Luciana Dias Ghiraldi-Lopes,Jean Eduardo Meneguello,Érika Seki Kioshima,Patrícia De Souza Bonfim-Mendonça

doi:10.3389/fcimb.2019.00230

Glaucia Sayuri Arita, Eduardo Jorge Pilau + Show 8 more

Open Access

https://doi.org/10.3389/fcimb.2019.00230

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Abstract

Candida albicans is the major pathogen isolated from nosocomial bloodstream infections, leading to higher mortality rates. Thus, due to its clinical relevance, studies aiming to understand host–pathogen interactions in C. albicans infection are necessary. Therefore, we performed proteomic analysis using a murine model of serial systemic infection by C. albicans to evaluate possible changes in the protein profile of the pathogen over time. Firstly, we observed a reduction in the median survival time of infected animals with increasing passage number, suggesting a higher pathogenicity acquired during repeated infections. By LC-MS/MS, it was possible to obtain protein profiles from the wild-type strain (WT) and compare them to proteins extracted from Candida cells recovered from infected tissues during passages one, three, and four (P1, P3, and P4). We obtained 56, 29, and 97 proteins in P1, P3, P4, respectively, all varying in abundance. Regarding biological processes, the majority of proteins were related to carbohydrate metabolism, stress responses and amino acid metabolism. The proteins were also categorized according to their potential role in virulence traits, such as biofilm production, yeast-to-hyphae transition, phenotypic switching, proteins related to stress responses, and uncharacterized proteins. Therefore, serial infection in combination with proteomic approach enabled us to deepen the existing knowledge about host-pathogen interactions.

Highlights

Candida spp. is one of the most common agents of nosocomial bloodstream infections worldwide, leading to high morbidity and mortality rates
The first step was to evaluate if serial infection, as represented in Figure 1A, could influence survival time in a murine model of systemic candidiasis
After adjusting the significance for multiple comparisons between each passage and the wild-type strain (WT), the median survival time was 10 days for the animals infected with the WT and P1 and 7 days for those infected with P2 (p = 0.3728 and p = 0.0472, respectively)

Summary

Introduction

Candida spp. is one of the most common agents of nosocomial bloodstream infections worldwide, leading to high morbidity and mortality rates. Some of the main risk factors associated with candidemia are the use of antimicrobial agents, corticosteroid usage, chemotherapy, hematological malignancies, central venous catheter usage, gastrointestinal surgery, parenteral nutrition, and hospitalization in the Intensive Care Unit (ICU), which facilitates dissemination of Candida among patients (Pfaller and Diekema, 2007). The risk of cross-transmission between healthcare workers’ hands and ICU surfaces by strains with greater expression of virulence factors has been previously described (Sakita et al, 2017). After serial passages through the kidney, strains were recovered with higher phenotypic variability (Lüttich et al, 2013); no overall virulence trend was observed. Other authors recovered a mutant defective in oxidative phosphorylation, but it was more resistant to phagocytosis and killing by neutrophils and macrophages after the fifth passage, demonstrating how C. albicans behaved in the infection (Cheng et al, 2007)

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