Candida Albicans Biofilm-Associated Resistance: Novel Liposomal Delivery System Fights Back

Researchers have found promise in inhibiting the formation of biofilms in C. albicans, known to create tolerance to many of the current antifungal treatment options. This liposomal formulation was able to disrupt the biofilms and allow for fluconazole to attack the infection using a lower dose.

Background

Candida albicans falls into a broader range of fungal infections called Candidiasis. Besides C. albicans, candidiasis has many different organisms like C. auris, C. glabrata, and C. krusei. C. albicans is the most common and the majority of suspected cases. Each organism is distinguished by varying budding, multicellular filaments, and gene expression. C. albicans infections can range from local mucosal to systemic infections. This allows for the widened range of scenarios that C. albicans can create — mild commensal cases to life-threatening cases.

C. albicans colonizes the mucosal surface. This colonization is most often asymptomatic and may only cause minor issues to the human host, if any. C. albicans can become symptomatic and a risk to the host when a disruption is caused to that environment or the host shows immune dysfunction. When a disruption is noted, C. albicans can spread rapidly, invading just about all reaches of the human host. Its ability to spread quickly is noted by its virulence factors. The central key to C. albicans pathogenesis is the ability of the pathogen to change its morphology and create biofilms. These biofilm formations push C. albicans from a commensal asymptomatic infection to a life-threatening resistant infection with high morbidity and mortality.

The C. albicans infection has a plethora of antifungal agents that can suppress its activity depending on how virulent it has become. Fluconazole, the flagship of the azole class, is widely used to treat C. albicans and often effective. Its effectiveness fades when the C. albicans infection morphs and creates biofilms. C. albicans biofilm-associated infections have increased tolerance to antimicrobial therapy, so the susceptibility to our current treatment options decline. Strategies to combat the biofilm issue only consist of a handful of agents. One new, novel strategy has shown promise in solving this increased tolerance and eliminating the biofilm formation.

Trial

A recent study published in the International Journal of Pharmaceutics has used a new liposomal delivery system to suppress the formation of biofilms in C. albicans. Along with fluconazole, a Pseudomonas aeruginosa quorum-sensing molecule (QSM), called N-3-oxo-dodecanoyl-L-homoserine lactone (C12AHL), was given in a liposomal formulation to patients. C12AHL is given because it has shown the ability to stop the C. albicans transition and the overall formation of biofilms. With the tolerance that biofilms create, eliminating the process that creates the biofilm should keep the C. albicans organism from becoming resistant.

The trial created four variations of the liposomal formulation to study in the patient population. L-F consisted of fluconazole only, L-H consisted of C12AHL only, L-HF consisted of fluconazole and C12AHL, and finally, L-C was the control with no drugs. It was found that L-H disrupted the biofilm and, in turn, allowed for increased efficacy of fluconazole. When L-HF was given, the biofilm was disrupted but it also killed the yeasts and diminished the yeast virulence at a significantly lower dose. The authors went on to state that:

“Therefore, liposomal co-formulation of C12AHL and fluconazole appears to be a promising approach to improve the efficacy of this common triazole against biofilm-mediated candidal infections.”

Conclusion

As time passes, organisms in this world adapt and grow resistant against many of the treatments we throw at them. The delivery system with C12AHL is one step forward in humanity’s attempt at adaption as well. If C12AHL can continue to become an effective treatment strategy in future studies, we may see a new door opening in how we go about treating and adapting to the new resistance we encounter.

Thank you for reading

Aaron Forsythe LECOM School of Pharmacy

References

Bandara, H M H N, et al. “A Novel, Quorum Sensor-Infused Liposomal Drug Delivery System Suppresses Candida Albicans Biofilms.” International Journal of Pharmaceutics, U.S. National Library of Medicine, 30 Mar. 2020, www.ncbi.nlm.nih.gov/pubmed/32006626.

Schell, WA. Biology of Candida Infections. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2020.

Tsui, Christina, et al. “Pathogenesis of Candida Albicans Biofilm.” Pathogens and Disease, Oxford University Press, June 2016, www.ncbi.nlm.nih.gov/pubmed/26960943.