Rise and fall of Caspofungin: the current status of Caspofungin as a treatment for Cryptococcus neoformans infection

Abstract

Antifungal infections are becoming a major concern to human health due to antimicrobial resistance. Echinocandins have been promising agents against resistant fungal infections, primarily caspofungin, which has a more effective mechanism of action than azoles and polyenes. However, fungi such as Cryptococcus neoformans appear to be inheritably resistant to these drugs, which is concerning due to the high clinical importance of C. neoformans. In this review, we review the history of C. neoformans and the treatments used to treat antifungals over the years, focusing on caspofungin, while highlighting the C. neoformans problem and possible explanations for its inherent resistance.

Plain language summary

Caspofungin is a drug used to treat several types of fungal infections. Resistance to caspofungin is a huge problem, especially in those that are immunocompromised. It is important to understand the history of caspofungin discovery, its clinical applications and its mechanism of action, as well as if a new drug target could be used overcome resistance. This review may perform guide new studies combining caspofungin with other drugs and indicate new potential targets for caspofungin.

Executive summary

Resistance to caspofungin

• Caspofungin arose as a new potential drug against fungi; however, the intrinsic resistance of some fungi shadowed its potential.

Synergism as an option to overcome resistance to caspofungin

• The combination with some antimicrobial peptides could help to bring back the effectiveness of caspofungin.

Application of bioinformatics

• Bioinformatics helped to find a new potential intracellular target for caspofungin.

New targets for caspofungin

• HDCA4 is a candidate for a new target of caspofungin once within the cell.

Future perspective

• Understanding the resistance of C. neoformans to caspofungin will help to overcome this problem.

Keywords: :

• Cryptococcus neoformans
• echinocandins
• glucan synthesis
• resistance

Author contributions

TKB Aguiar, ACM Costa, NAS Neto, DMS Brito, CDT Freitas, JMM Neto, FP Mesquita and PFN Souza performed the conception, and the study design was written and approved the final version for submission.

Financial disclosure

PFN Souza is thankful for the senior researcher grant from CNPq at process number 305003/2022-4. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

PFN Souza is thankful for the senior researcher grant from CNPq at process number 305003/2022-4.