Cefepime and Amoxicillin Increase Metabolism and Enhance Caspofungin Tolerance of Candida albicans Biofilms.

Rossana De Aguiar Cordeiro,Jonathas Sales De Oliveira,José Júlio Costa Sidrim,Patrícia Bruna Leite Mendes,Ana Raquel Colares De Andrade,Reginaldo Gonçalves Lima-Neto,Marcos Fábio Gadelha Rocha,Débora Castelo Brancode Souza Collares Maia,Raimunda Nogueira Brilhante,Vandbergue Santos Pereira,Lucas Pereira De Alencar,Antonio Jose De Jesus Evangelista,Rosana Serpa

doi:10.3389/fmicb.2019.01337

Abstract

It is well known that prolonged antibiotic therapy alters the mucosal microbiota composition, increasing the risk of invasive fungal infection (IFI) in immunocompromised patients. The present study investigated the direct effect of β-lactam antibiotics cefepime (CEF) and amoxicillin (AMOX) on biofilm production by Candida albicans ATCC 10231. Antibacterials at the peak plasmatic concentration of each drug were tested against biofilms grown on polystyrene surfaces. Biofilms were evaluated for biomass production, metabolic activity, carbohydrate and protein contents, proteolytic activity, ultrastructure, and tolerance to antifungals. CEF and AMOX enhanced biofilm production by C. albicans ATCC 10231, stimulating biomass production, metabolic activity, viable cell counts, and proteolytic activity, as well as increased biovolume and thickness of these structures. Nevertheless, AMOX induced more significant changes in C. albicans biofilms than CEF. In addition, it was shown that AMOX increased the amount of chitin in these biofilms, making them more tolerant to caspofungin. Finally, it was seen that, in response to AMOX, C. albicans biofilms produce Hsp70 – a protein with chaperone function related to stressful conditions. These results may have a direct impact on the pathophysiology of opportunistic IFIs in patients at risk.

Highlights

Invasive fungal infections (IFIs) are a serious public health problem worldwide, as they result in approximately 90% mortality in immunocompromised patients, such as severe neutropenic transplant patients using high doses of corticoids and HIV-positive individuals (Hahn-Ast et al, 2010; Mariette et al, 2017)
The biofilms of C. albicans ATCC 10231 were formed in 96-well flat bottom microtiter plates with an initial inoculum of approximately 3 × 106 cells/ml in RPMI-1640 medium supplemented with CEF or AMOX
AMOX increased the amount of chitin in C. albicans ATCC 10231 biofilms after 48 h of maturation (Figure 1D) (P < 0.05)

Summary

Introduction

Invasive fungal infections (IFIs) are a serious public health problem worldwide, as they result in approximately 90% mortality in immunocompromised patients, such as severe neutropenic transplant patients using high doses of corticoids and HIV-positive individuals (Hahn-Ast et al, 2010; Mariette et al, 2017). Such infections are usually aggravated when biofilm-forming pathogens are involved (Vogel et al, 2013; Johnson et al, 2016). Antibiotic therapy is a determining risk factor for the development of IFI in immunocompromised patients (Bongomin et al, 2017)

Methods

Results

Conclusion