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

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.

Discovery of Novel Resistance Mechanisms of Vibrio parahaemolyticus Biofilm against Aminoglycoside Antibiotics

“…In addition, the average thickness of the V. parahaemolyticus biofilm was significantly correlated with the BIC for amikacin ( p < 0.05). Cordeiro et al demonstrated the enhanced antibiotic resistance of microbial cells after the treatment of Candida albicans with the β-lactam antibiotics cefepime and amoxicillin, and concluded that antibiotics stimulated biomass production and increased the biological volume and average thickness of these structures [ 31 ].…”

Rapid Detection of Echinocandins Resistance by MALDI-TOF MS in Candida parapsilosis Complex

“…Incidence of invasive fungal infections (IFIs) has tragically increased during the last twenty years, despite advances in methods of diagnosis [1,2]. Candida-related IFIs are linked to elevated morbidity and mortality, as well as a high cost of healthcare [1,2].…”

“…Incidence of invasive fungal infections (IFIs) has tragically increased during the last twenty years, despite advances in methods of diagnosis [1,2]. Candida-related IFIs are linked to elevated morbidity and mortality, as well as a high cost of healthcare [1,2]. Candida albicans is still the major species related to candidemia wide world; however, the diversity of other Candida species differs according geographical location.…”

Interactions between Candida albicans and the resident microbiota

“…The β-lactam antibiotics, such as cefepime, amoxicillin, and vancomycin, can stimulate the in vitro planktonic growth of C. albicans in 96-well plates and in vivo virulence tested with Caenorhabditis elegans infection model ( Aguiar Cordeiro et al, 2018 ). Cefepime and amoxicillin also directly stimulate C. albicans metabolism and biofilm formation in 96-well plates, thereby enhancing antifungal tolerance ( Cordeiro et al, 2019 ). Gut bacteria treated with β-lactam antibiotics released significant amounts of peptidoglycan fragments, a procedure so called “a peptidoglycan storm” ( Tan et al, 2021 ), which strongly stimulated hyphal formation in C. albicans in vitro and in vivo ( Xu et al, 2008 ; Tan et al, 2021 ).…”