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1.
Future Microbiol ; 19(7): 621-630, 2024.
Article in English | MEDLINE | ID: mdl-38497911

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.


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.


Subject(s)
Antifungal Agents , Caspofungin , Cryptococcosis , Cryptococcus neoformans , Drug Resistance, Fungal , Caspofungin/therapeutic use , Caspofungin/pharmacology , Cryptococcus neoformans/drug effects , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Humans , Cryptococcosis/drug therapy , Cryptococcosis/microbiology , Echinocandins/therapeutic use , Echinocandins/pharmacology , Animals , Microbial Sensitivity Tests , Lipopeptides/therapeutic use , Lipopeptides/pharmacology
2.
Future Microbiol ; 17: 1133-1146, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35880557

ABSTRACT

Introduction: Candida krusei and Candida albicans are biofilm-forming drug-resistant yeasts that cause bloodstream infections that can lead to death. Materials & methods: nystatin and itraconazole were combined with two synthetic peptides, PepGAT and PepKAA, to evaluate the synergistic effect against Candida biofilms. Additionally, scanning electron and fluorescence microscopies were employed to understand the mechanism behind the synergistic activity. Results: Peptides enhanced the action of drugs to inhibit the biofilm formation of C. krusei and C. albicans and the degradation of mature biofilms of C. krusei. In combination with antifungal drugs, peptides' mechanism of action involved cell wall and membrane damage and overproduction of reactive oxygen species. Additionally, in combination, the peptides reduced the toxicity of drugs to red blood cells. Conclusion: These results reveal that the synthetic peptides enhanced the antibiofilm activity of drugs, in addition to reducing their toxicity. Thus, these peptides have strong potential as adjuvants and to decrease the toxicity of drugs.


Candida krusei and Candida albicans are biofilm-forming, drug-resistant yeasts that cause bloodstream infections that can lead to death. In this study, biofilms of C. krusei and C. albicans were treated with a solution composed of synthetic peptides and antifungal drugs, none of which were effective alone. The synthetic peptides reduced the toxicity of drugs to red blood cells. These results may pave the way to the application of synthetic peptides as a beneficial additional to antifungal drugs to treat fungi that cannot be killed by drugs alone.


Subject(s)
Antifungal Agents , Candida , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Biofilms , Candida albicans , Microbial Sensitivity Tests , Peptides/pharmacology
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