Article
Microbiology
Masakazu Niimi, Kyoko Niimi, Koichi Tanabe, Richard D. Cannon, Erwin Lamping
Summary: Overexpression of ATP-binding cassette (ABC) transporters is the main cause of drug resistance in fungal pathogens. Milbemycins, enniatin B, beauvericin, and FK506 are potential broad-spectrum fungal multidrug efflux pump inhibitors. Investigating naturally generated inhibitor-resistant mutants can provide insights into the structure-activity relationships in ABC transporters.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Hongkang Wang, Zhe Ji, Yanru Feng, Tianhua Yan, Yongbing Cao, Hui Lu, Yuanying Jiang
Summary: Inhibiting sphingolipid biosynthesis to block membrane localization and inactivate Cdr1 was found to enhance the antifungal activity of azoles against azole-resistant C. albicans, suggesting its therapeutic potential.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mohammad Imran Khan, Hani Choudhry, Sadaf Jahan, Irfan A. A. Rather
Summary: With the increasing prevalence of multi-drug-resistant fungal infections, especially in developing countries, the development of new strategies and drugs to overcome drug resistance in fungal pathogens is crucial. This study investigated the potential of human neutrophil peptide (HNP) as a treatment for Candida infections. Results showed that HNP alone and in combination with fluconazole (FLC) exhibited antifungal activity against both susceptible and resistant C. albicans isolates. Furthermore, HNP inhibited biofilm formation and the activity of drug efflux pumps and their genes. These findings suggest that HNP could be used as a monotherapy or in combination with FLC to treat azole-resistant C. albicans.
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
Dentistry, Oral Surgery & Medicine
Cesar Augusto Abreu-Pereira, Marlise Inez Klein, Carmelia Isabel Vitorino Lobo, Ana Luiza Gorayb Pereira, Claudia Carolina Jordao, Ana Claudia Pavarina
Summary: This study evaluated the effectiveness of DNase I combined with antimicrobial photodynamic therapy against biofilms formed by a fluconazole-resistant Candida albicans strain. The results showed that DNase treatment combined with aPDT could significantly reduce cell viability and the components of the biofilm.
Article
Microbiology
Majid Rasool Kamli, Elham A. Alzahrani, Soha M. Albukhari, Aijaz Ahmad, Jamal S. M. Sabir, Maqsood Ahmad Malik
Summary: This study describes a seedless biogenic synthesis of Ag-Ni bimetallic nanoparticles that exhibit potent antifungal activity against FLZ-resistant C. albicans. The combination of Ag-Ni NPs with FLZ shows synergistic effects, inhibiting biofilm formation and efflux pump function in C. albicans.
Article
Biotechnology & Applied Microbiology
Y. Tsukuda, N. Mizuhara, Y. Usuki, Y. Yamaguchi, A. Ogita, T. Tanaka, K. Fujita
Summary: Anethole, a phenylpropanoid compound, shows synergistic antifungal activity when combined with other drugs, with potency being influenced by the length of the p-alkyl chain and the methoxy group of anethole. The presence of a double bond in the propenyl group did not significantly impact antifungal potency. Production of reactive oxygen species and inhibition of drug efflux also played roles in the antifungal activities observed.
LETTERS IN APPLIED MICROBIOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Feng Gu, Shan Hu, Yunjian Wu, Changyu Wu, Ying Yang, Bing Gu, Hong Du
Summary: This study successfully detected the drug resistance of non-Candida albicans using SERS technology combined with OPLS-DA analysis. The method is non-destructive to the cell wall and easy to operate, showing promising clinical application potential.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Chemistry, Medicinal
Sandra Kovachka, Giuliano Malloci, Meline Simsir, Paolo Ruggerone, Stephane Azoulay, Isabelle Mus-Veteau
Summary: This review focuses on the biological evaluation and molecular mechanistic insights of inhibitors of the drug efflux activity of the Hedgehog receptor Patched1 (Ptch1). Ptch1 is known to be over-expressed in many types of cancers and plays a role in the resistance to chemotherapy of cancer cells. Inhibition of Ptch1 has been shown to improve the efficacy of chemotherapy without toxicity for healthy cells or potential side effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Lucas Prestianni, Eric R. Espinal, Sarah F. Hathcock, Nadine Vollmuth, Pixiang Wang, Robert A. Holler, Shaoyang Liu, Brandon J. Kim, Yuping Bao
Summary: In this study, the formation of quercetin-iron complex nanoparticles was systematically investigated to improve the aqueous solubility and stability of quercetin. It was found that the nanoparticles greatly enhanced the stability and solubility of quercetin, leading to enhanced antioxidant activities and extended effects. Preliminary cellular evaluation also indicated the potential of these nanoparticles for cancer treatment, as they exhibited minimal cytotoxicity and effectively blocked the efflux pump of cells.
Article
Infectious Diseases
Hsu-Feng Lu, Yu-Chieh Tsai, Li-Hua Li, Yi-Tsung Lin, Tsuey-Ching Yang
Summary: AzoR, a LysR-type transcriptional regulator, was found to negatively regulate the expression of the smeU1VWU2X operon and the SmeVWX pump-mediated antibiotic resistance in Stenotrophomonas maltophilia.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Microbiology
Rui Yuan, Jie Tu, Chunquan Sheng, Xi Chen, Na Liu
Summary: The Hsp90 inhibitor ganetespib shows excellent synergistic antifungal activity in vitro against azole-resistant Candida albicans, significantly inhibiting fungal biofilm formation and down-regulating key resistance genes. In a mouse model, the combination of ganetespib and fluconazole effectively reverses fluconazole resistance and decreases fungal load in the kidneys.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Jiadi Shen, Ming Ma, Wei Duan, Yun Huang, Banruo Shi, Qiaochu Wu, Xin Wei
Summary: This study aimed to investigate the effects of an activator and an inhibitor of autophagy on the susceptibility of C. albicans biofilms to antifungal agents and the related mechanisms. It was found that the autophagic activity of C. albicans biofilms was closely related to their susceptibility to antifungal agents.
Article
Infectious Diseases
Carmen-Ecaterina Leferman, Laura Stoica, Mirela Tiglis, Bogdan Alexandru Stoica, Monica Hancianu, Alin Dumitru Ciubotaru, Delia Lidia Salaru, Aida Corina Badescu, Camelia-Margareta Bogdanici, Ioan-Adrian Ciureanu, Cristina-Mihaela Ghiciuc, Mark G. Moloney, Sonia Silva
Summary: The combination of chemical and photodynamic therapy (PDT) can effectively inhibit the growth of fluconazole-resistant clinical Candida albicans, addressing the challenge of multidrug-resistant yeast.
Article
Microbiology
Stuart Cannon, William Kay, Sreedhar Kilaru, Martin Schuster, Sarah Jane Gurr, Gero Steinberg
Summary: Global banana production is facing challenges from Panama disease, but there are currently no effective fungicide-based strategies to control it. Research found that the pathogen causing Panama disease, FocTR4, has innate resistance to all single-site fungicides but little resistance to multi-site fungicides. Only a few fungicides have been shown to effectively suppress the disease in soil-grown bananas.
