Article
Microbiology
Nancy E. Scott, Serin Edwin Erayil, Susan E. Kline, Anna Selmecki
Summary: The rare Candida (Clavispora) lusitaniae species can rapidly acquire multidrug resistance and cause life-threatening infections in hospital settings. However, the mutations causing this antifungal drug resistance are poorly understood. In a study involving an individual patient, it was found that the evolution of multidrug resistance in C. lusitaniae can occur during treatment with first-line antifungal therapy, and an ERG3 gene mutation was associated with cross-resistance to multiple drug classes.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Yao Wang, Xin Fan, He Wang, Timothy Kudinha, Ya-Ning Mei, Fang Ni, Yu-Hong Pan, Lan-Mei Gao, Hui Xu, Hai-Shen Kong, Qing Yang, Wei-Ping Wang, Hai-Yan Xi, Yan-Ping Luo, Li-Yan Ye, Meng Xiao
Summary: The study found that azole resistance in C. tropicalis causing invasive candidiasis in China has been increasing, particularly to fluconazole, with a high rate of cross-resistance to voriconazole. Despite low echinocandin resistance, multi-drug resistance was observed in some isolates, indicating a growing nationwide challenge that requires effective interventions.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Laura S. Burrack, Robert T. Todd, Natthapon Soisangwan, Nathan P. Wiederhold, Anna Selmecki
Summary: Antifungal drug resistance and tolerance are a serious threat to global public health. This study investigated the evolution of drug resistance in Candida auris and found rapid acquisition of resistance mutations and the stability of resistance in the absence of drugs. The genetic background of clinical isolates was also found to affect the evolutionary potential and acquisition of resistance. These findings highlight the high stability and high rates of acquisition of antifungal resistance in C. auris, which can lead to the evolution of pan-resistant isolates in clinical settings.
Article
Microbiology
Milena Kordalewska, Geselle Cancino-Prado, Joao Nobrega de Almeida Jr, Igor Brasil Brandao, Renata Tigulini de Souza Peral, Arnaldo. L. L. Colombo, David. S. S. Perlin
Summary: We investigated the echinocandin susceptibility and FKS1 genotypes in clinical isolates of Candida auris from patients in Salvador, Brazil. Three isolates with a novel FKS1 mutation were found to be resistant to echinocandins, causing elevated minimum inhibitory concentrations. Introduction of the Fks1 W691L mutation into susceptible strains also resulted in increased resistance to echinocandins.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Immunology
Jie Tu, Tianbao Zhu, Qingwen Wang, Wanzhen Yang, Yahui Huang, Defeng Xu, Na Liu, Chunquan Sheng
Summary: Candida auris is a serious public health threat that has caused a global epidemic due to its multi-drug resistance, remarkable transmissibility, and high mortality. A novel benzoanilide antifungal agent, compound A1, was discovered through a comprehensive strategy involving phenotypic screening, hit optimization, antifungal assays, and mechanism exploration. Compound A1 showed potent efficacy against Candida auris infection both in vitro and in vivo. Mechanistic investigation revealed that compound A1 inhibited the biosynthesis of virulence factors and fungal cell walls by blocking glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Therefore, compound A1 represents a promising lead compound for combating drug-resistant candidiasis.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Microbiology
Maiko Kiyohara, Taiga Miyazaki, Michiyo Okamoto, Tatsuro Hirayama, Koichi Makimura, Hiroji Chibana, Nana Nakada, Yuya Ito, Makoto Sumiyoshi, Nobuyuki Ashizawa, Kazuaki Takeda, Naoki Iwanaga, Takahiro Takazono, Koichi Izumikawa, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae
Summary: Worldwide, there have been outbreaks of invasive infections caused by multidrug-resistant Candida auris, which has a high mortality rate. This study identified a novel resistance mutation (G4061A inducing R1354H) in the FKS1 gene of a caspofungin-resistant clinical isolate. Through the CRISPR-Cas9 system, a recovered strain (H1354R) was generated, in which only this single nucleotide mutation was reverted to its wild-type sequence. The study also analyzed the antifungal susceptibility of mutant strains with only the R1354H mutation introduced into C. auris wild-type strains.
Editorial Material
Microbiology
Vikas Yadav, Joseph Heitman
Summary: The emergence of Candida auris has raised concerns about antifungal drug resistance. This strain exhibits resistance to all antifungal drugs at a very high rate. The study suggests that the presence of C. auris on apples treated with antifungals may contribute to the evolution of drug-resistant isolates.
Review
Infectious Diseases
Rashi Verma, Dibyabhaba Pradhan, Ziaul Hasan, Harpreet Singh, Arun Kumar Jain, Luqman Ahmad Khan
Summary: This study presents the distribution and antifungal resistance patterns of Candida species among the Indian population, which could assist in forming treatment recommendations for the region and beyond in the future.
Article
Infectious Diseases
Farnaz Daneshnia, Amir Arastehfar, Lisa Lombardi, Ulrike Binder, Jakob Scheler, Roya Vahedi Shahandashti, Ferry Hagen, Cornelia Lass-Floerl, Michael K. Mansour, Geraldine Butler, David S. Perlin
Summary: Candida parapsilosis is a significant cause of candidemia worldwide. Mutations in the FKS1 gene outside the hotspot regions can result in a higher level of echinocandin tolerance, potentially leading to the development of echinocandin resistance. This study supports the cataloging of these mutations for better understanding and management of Candida parapsilosis infections.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Review
Pharmacology & Pharmacy
Jie Tu, Na Liu, Yahui Huang, Wanzhen Yang, Chunquan Sheng
Summary: Candida auris is a major global threat to human health due to its strong drug resistance. This review provides a comprehensive overview of current strategies, drug candidates, and lead compounds for the treatment of C. auris. The resistance profiles and mechanisms are summarized, and the structures and activities of clinical candidates, drug combinations, antifungal chemosensitizers, repositioned drugs, new targets, and new types of compounds are discussed in detail. The review also offers perspectives for guiding future research in this field.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Immunology
Jeremy A. W. Gold, Emma E. Seagle, Joelle Nadle, Devra M. Barter, Christopher A. Czaja, Helen Johnston, Monica M. Farley, Stepy Thomas, Lee H. Harrison, Jill Fischer, Brittany Pattee, Rajal K. Mody, Erin C. Phipps, Sarah Shrum Davis, Brenda L. Tesini, Alexia Y. Zhang, Tiffanie M. Markus, William Schaffner, Shawn R. Lockhart, Snigdha Vallabhaneni, Brendan R. Jackson, Meghan Lyman
Summary: The study found that a considerable proportion of patients with candidemia were initially treated with fluconazole, which may not be appropriate for cases involving non-albicans or fluconazole-resistant species. Therefore, it is important to evaluate the reasons for nonadherence to treatment guidelines and provide clinician education.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Lynn Miesel, Melanie T. Cushion, Alan Ashbaugh, Santiago R. Lopez, Voon Ong
Summary: Rezafungin, a novel echinocandin, has shown efficacy against Candida, Aspergillus, and Pneumocystis in prophylactic studies. By reducing fungal burden and preventing infection, it has the potential to be a single-agent prophylaxis against invasive fungal diseases caused by these pathogens.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Milena Radunovic, Milena Barac, Jovana Kuzmanovic Pficer, Dusan Pavlica, Aleksandar Jovanovic, Ana Pucar, Sanja Petrovic
Summary: The aim of this study was to compare the antifungal susceptibility of Candida isolated from the tongue and subgingival biofilm. The results showed that both tongue and subgingival isolates were susceptible to amphotericin B. Tongue isolates were more susceptible to fluconazole, while subgingival isolates showed lower susceptibility to itraconazole. The study also found a correlation between the susceptibility of C. albicans to antifungals and oral hygiene and moderate periodontal destruction.
Article
Microbiology
Cecilia G. Carvalhaes, Abby L. Klauer, Paul R. Rhomberg, Michael A. Pfaller, Mariana Castanheira
Summary: Rezafungin is a new echinocandin with potent activity against candidemia and invasive candidiasis. It also shows activity against Aspergillus isolates. The new CLSI breakpoints are important for understanding the susceptibility of Candida spp. and rezafungin.
JOURNAL OF CLINICAL MICROBIOLOGY
(2022)
Article
Microbiology
Ali Korhan Sig, Meliha Cagla Sonmezer, Dolunay Gulmez, Serhat Duyan, Omrum Uzun, Sevtap Arikan-Akdagli
Summary: The frequency of invasive fungal infections is increasing, with a shift towards non-albicans Candida species. This includes the emergence of echinocandin resistance in Candida glabrata, highlighting the importance of routine antifungal susceptibility testing and clinical attention to this trend.
