Candida albicans enhances meropenem tolerance of Pseudomonas aeruginosa in a dual-species biofilm

Abstract

Background Pseudomonas aeruginosa is an opportunistic bacterium that infects the airways of cystic fibrosis patients, surfaces of surgical and burn wounds, and indwelling medical devices. Patients are prone to secondary fungal infections, with Candida albicans being commonly co-isolated with P. aeruginosa. Both P. aeruginosa and C. albicans are able to form extensive biofilms on the surfaces of mucosa and medical devices. Objectives To determine whether the presence of C. albicans enhances antibiotic tolerance of P. aeruginosa in a dual-species biofilm. Methods Single- and dual-species biofilms were established in microtitre plates and the survival of each species was measured following treatment with clinically relevant antibiotics. Scanning electron microscopy and confocal microscopy were used to visualize biofilm structure. Results C. albicans enhances P. aeruginosa biofilm tolerance to meropenem at the clinically relevant concentration of 5 mg/L. This effect is specific to biofilm cultures and is dependent upon C. albicans extracellular matrix polysaccharides, mannan and glucan, with C. albicans cells deficient in glycosylation structures not enhancing P. aeruginosa tolerance to meropenem. Conclusions We propose that fungal mannan and glucan secreted into the extracellular matrix of P. aeruginosa/C. albicans dual-species biofilms play a central role in enhancing P. aeruginosa tolerance to meropenem, which has direct implications for the treatment of coinfected patients.

Immune Sensing of Candida albicans

“…These infections are commonly associated with biofilm formation, especially in patients with dentures, voice protheses and xerostomia (reduced or absent saliva flow). Biofilm formation makes these infections difficult to treat because they are generally polymicrobial in nature, and the production of extracellular matrix increases the resistance to antimicrobial therapy [ 5 , 6 , 84 ]. Oral candidiasis is prevalent in immunosuppressed individuals such as HIV patients, mouth and throat cancer patients, and patients taking oral steroids making them highly susceptible to infection.…”

How Bacterial Adaptation to Cystic Fibrosis Environment Shapes Interactions Between Pseudomonas aeruginosa and Staphylococcus aureus

“…However, it appears that these microorganisms are not powerless in front of P. aeruginosa and can even take advantage of this interaction within mixed-species biofilm. Antimicrobial resistance and virulence of C. albicans and P. aeruginosa are thus enhanced during their interaction, particularly through an increased production of phenazines by P. aeruginosa and ethanol by C. albicans ( Fourie et al, 2016 ; O’Brien and Fothergill, 2017 ; Fourie and Pohl, 2019 ; Alam et al, 2020 ; Bandara et al, 2020 ; Hùlková et al, 2020 ; Ibberson and Whiteley, 2020 ). In the same way, P. aeruginosa alginate can protect B. cenocepacia from the host immune system ( O’Brien and Fothergill, 2017 ).…”

Polymicrobial Interactions in the Cystic Fibrosis Airway Microbiome Impact the Antimicrobial Susceptibility of Pseudomonas aeruginosa

“…albicans enhanced P. aeruginosa ECM production, consisting of proteins, polysaccharides, and nucleic acids, through increased expression of the alginate genes AlgU and mucA [171]. Alam et al (2019) showed C. albicans can enhance meropenem tolerance of P. aeruginosa in a dual-species biofilm [172]. They concluded that fungal mannan and glucan secreted into the ECM of a dual species biofilm of P. aeruginosa and C. albicans increases P. aeruginosa tolerance to meropenem.…”