Impact of manganese on biofilm formation and cell morphology of Candida parapsilosis clinical isolates with different biofilm forming abilities

Abstract

The commensal species Candida parapsilosis is an emerging human pathogen that has the ability to form biofilms. In this study, we explored the impact of the divalent cations cobalt (Co2+), copper (Cu2+), iron (Fe3+), manganese (Mn2+), nickel (Ni2+) and zinc (Zn2+) on biofilm formation of clinical isolates of C. parapsilosis with no, low and high biofilm forming abilities at 30 and 37°C. All strains besides one isolate showed a concentration-dependent enhancement of biofilm formation at 30°C in the presence of Mn2+ with a maximum at 2 mM. The biofilm forming ability of no and low biofilm forming isolates was >2-fold enhanced in the presence of 2 mM Mn2+, while the effect in high biofilm forming isolate was significantly less pronounced. Of note, cells in the biofilms of no and low biofilm forming strains differentiated into yeast and pseudohyphal cells similar in morphology to high biofilm formers. The biofilm transcriptional activator BCR1 has a dual developmental role in the absence and presence of 2 mM Mn2+ as it promoted biofilm formation of no biofilm forming strains, and, surprisingly, suppressed cells of no biofilm forming strains to develop into pseudohyphae and/or hyphae. Thus, environmental conditions can significantly affect the amount of biofilm formation and cell morphology of C. parapsilosis with Mn2+ to overcome developmental blocks to trigger biofilm formation and to partially relieve BCR1 suppressed cell differentiation.

The oral cavity promotes virulence of Candida parapsilosis sensu stricto via up-regulation of BCR1

“…This finding demonstrates the ability of BCR1 to respond to signals from the environment. In agreement with the findings of Shafeeq et al [37], and under our experimental conditions, the basal transcriptional activity of BCR1 was shown to be higher in those isolates that recovered under conditions of gingivoperiodontal disease. This condition is characterized by the imbalance of the colonizing microbiota, with a periodontopathogen predominance of the red and orange complex [38], in addition to the REDOX imbalance [39,40].…”

“…On the other hand, Shafeeq and his group [37] published in 2019 a study in which they demonstrate the property of BCR1 to respond to high levels of manganese, which led to the formation of biofilm in strains previously defined as nonforming and low biofilm-forming. This finding demonstrates the ability of BCR1 to respond to signals from the environment.…”

Iron Metabolism, Pseudohypha Production, and Biofilm Formation through a Multicopper Oxidase in the Human-Pathogenic Fungus Candida parapsilosis

“…Additionally, deletion of the multicopper oxidase gene CaFET34, but not deletion of CaFET33, significantly attenuated the filamentous growth of C. albicans (25). In the case of C. parapsilosis, Shafeeq et al showed Mn ϩϩ -dependent biofilm formation through the activity of the biofilm regulator BCR1 (41). All these data prompted us to investigate whether a similar effect occurs in C. parapsilosis.…”

Evaluation of Biofilm Formation in Candida tropicalis Using a Silicone-Based Platform with Synthetic Urine Medium

“…The adherence ability of Staphylococcus epidermidis is enhanced in low concentrations of magnesium [42]. In C. parapsilosis, an increase in Mn 2+ , with a maximum at 2 mM, significantly induced biofilm formation [43]. Moreover, different metal ions can suppress or enhance C. albicans and C. tropicalis biofilm formation.…”