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)
Review
Pharmacology & Pharmacy
Eve W. L. Chow, Li Mei Pang, Yue Wang
Summary: Many human fungal pathogens are opportunistic, becoming infectious when the host's immunity and microbiome are compromised. Bacteria in the human microbiome play a crucial role in keeping fungi harmless and defending against fungal infection. The Human Microbiome Project has significantly advanced our understanding of the interaction between bacteria and fungi, providing insights for developing antifungal strategies.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Microbiology
Olabayo H. Ajetunmobi, Gina Wall, Bruna Vidal Bonifacio, Lucero A. Martinez Delgado, Ashok K. Chaturvedi, Laura K. Najvar, Floyd L. Wormley Jr, Hoja P. Patterson, Nathan P. Wiederhold, Thomas F. Patterson, Jose L. Lopez-Ribot
Summary: Candidiasis is a common nosocomial infection, and the emergence of drug-resistant pathogens has increased the need for new therapies. Researchers have repurposed existing drugs and identified three compounds that have potential in inhibiting biofilm formation and exhibiting antifungal activity against Candida species.
Review
Microbiology
Shanthini Kalimuthu, Om Alkhir Alshanta, Akshaya Lakshmi Krishnamoorthy, Akhila Pudipeddi, Adline Princy Solomon, William McLean, Yiu Yan Leung, Gordon Ramage, Prasanna Neelakantan
Summary: Fungal infections are difficult to diagnose and treat effectively due to the similarities between fungi and human cells. Candida albicans, a common opportunistic pathogen, has shown resistance to current antifungal drugs. This review focuses on the use of small-molecule anti-virulence approaches to tackle C. albicans infections.
CRITICAL REVIEWS IN MICROBIOLOGY
(2022)
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
Chemistry, Medicinal
Simon D. P. Baugh, Anna Chaly, Damian G. Weaver, Jeffrey C. Pelletier, Sandeep Thanna, Katie B. Freeman, Allen B. Reitz, Richard W. Scott
Summary: The research team has developed a series of non-peptide antifungal analogs through chemical optimization, resulting in highly potent, broad-spectrum compounds with low mammalian cell cytotoxicity. These compounds have the potential to become new antifungal agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Pharmacology & Pharmacy
Valeria Marrocco, Tuan Tran, Siying Zhu, Seung Hyuk Choi, Ana M. Gamo, Sijia Li, Qiangwei Fu, Marta Diez Cunado, Jason Roland, Mitch Hull, Van Nguyen-Tran, Sean Joseph, Arnab K. Chatterjee, Nikki Rogers, Matthew S. Tremblay, Weijun Shen
Summary: The text discusses the unfolded protein response (UPR) and cellular stress mechanisms, and the identification of a small molecule through high-throughput screening that can modulate UPR and ER stress. This compound demonstrates potential therapeutic effects in in vivo disease models.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Biochemistry & Molecular Biology
Stephanie Nguyen, Jia Q. Truong, John B. Bruning
Summary: Invasive fungal infections pose a serious threat to human health, necessitating the development of novel antifungal drugs. Targeted interruption of essential metabolic pathways in fungi shows promise as a strategy to disrupt fungal survival and virulence.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Microbiology
Helal F. Hetta, Yasmin N. Ramadan, Israa M. S. Al-Kadmy, Noura H. Abd Ellah, Lama Shbibe, Basem Battah
Summary: A multidrug-resistant pathogenic yeast called Candida auris can quickly spread among hospitalized and immunodeficient patients, causing nosocomial outbreaks and potentially pandemic outbreaks in 45 nations with high mortality rates. It has become resistant to decontamination techniques and can survive for weeks in hospitals. Nanoparticles have emerged as a promising treatment for diseases caused by this newly discovered pathogen, and are currently being researched as an effective solution against C. auris.
Article
Microbiology
Katura Metzner, Matthew J. O'Meara, Benjamin Halligan, Jesse W. Wotring, Jonathan Z. Sexton, Teresa R. O'Meara
Summary: Fungal pathogens like Candida albicans can cause devastating human disease, but there is high resistance to antifungal therapies. Targeting virulence factors is a new approach to antimicrobial development, and we identified NSC 697923 as a compound that blocks the hyphal transition in C. albicans by targeting eIF3.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Robert Zarnowski, Anna Jaromin, Agnieszka Zagorska, Eddie G. Dominguez, Katarzyna Sidoryk, Jerzy Gubernator, David R. Andes
Summary: The study demonstrated that DiMIQ inhibits Candida albicans biofilm formation by altering fungal cell walls and extracellular matrix, while affecting various metabolic pathways. It may provide a potent alternative for treating biofilm-associated Candida infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Mojtaba Didehdar, Zahra Chegini, Aref Shariati
Summary: Eugenol, a natural compound found in clove and cinnamon essential oil, shows potential therapeutic effects against candidiasis by inhibiting Candida growth and virulence factors. It disrupts Candida cell metabolism and structure, increases membrane permeability, inhibits adhesion and biofilm formation, and enhances the efficacy of antifungal drugs. Further research is needed to validate its effectiveness and safety.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Microbiology
Paulo Henrique Fonseca do Carmo, Maira Terra Garcia, Livia Mara Alves Figueiredo-Godoi, Anna Carolina Pinheiro Lage, Newton Soares da Silva, Juliana Campos Junqueira
Summary: Candidiasis is a common fungal infection caused by Candida albicans. Current antifungal treatments have limitations such as toxicity and drug resistance, leading to the exploration of nanocarrier systems like metal nanoparticles. This review focuses on the use of silver, gold, and iron nanoparticles as potential antifungal agents against C. albicans, discussing their mechanism of action and potential for reducing drug resistance.
Article
Multidisciplinary Sciences
Houda G. Khaled, Hongxuan Feng, Xin Hu, Xin Sun, Wang Zheng, Pan P. Li, Dobrila D. Rudnicki, Wenjuan Ye, Yu-Chi Chen, Noel Southall, Juan Marugan, Christopher A. Ross, Marc Ferrer, Mark J. Henderson, Russell L. Margolis
Summary: The study identified 898 potentially effective compounds for modifying HTT and HTT-AS promoter activity. However, challenges remain in finding a small molecule approach for HTT suppression without affecting cell viability.
SCIENTIFIC REPORTS
(2021)
Article
Infectious Diseases
Weifeng Hao, Dan Qiao, Ying Han, Ning Du, Xuefen Li, Yufeng Fan, Xuejun Ge, Heyu Zhang
Summary: This study identified five compounds with strong antifungal activities against Candida strains, among which disulfiram showed the most promising results, particularly in inhibiting biofilm formation.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Chaminda J. Seneviratne, Preethi Balan, Kwan Ki Karrie Ko, Nadeeka S. Udawatte, Deborah Lai, Dorothy Hui Lin Ng, Indumathi Venkatachalam, Kheng Sit Lim, Moi Lin Ling, Lynette Oon, Bee Tin Goh, Xiang Ying Jean Sim
Summary: The study found that using cetylpyridinium chloride and povidone-iodine mouth rinses can effectively reduce the salivary SARS-CoV-2 viral load in COVID-19 patients. Especially in high-risk procedures such as dental treatment, using these mouth rinses may help reduce the risk of virus transmission.
Review
Dentistry, Oral Surgery & Medicine
Ethan Ng, John R. H. Tay, P. Balan, Marianne M. A. Ong, Nagihan Bostanci, Georgios N. Belibasakis, Chaminda J. Seneviratne
Summary: Open-ended molecular techniques like 16S rRNA sequencing have shown that the oral bacteriome of subgingival plaque is more diverse than previously thought. Low abundance species can also play critical roles in global community dysbiosis, and coordinated interactions within the community are essential for disease pathogenesis.
JOURNAL OF PERIODONTAL RESEARCH
(2021)
Review
Microbiology
Lean Heong Foo, Preethi Balan, Li Mei Pang, Marja L. Laine, Chaminda Jayampath Seneviratne
Summary: Halitosis or oral malodor is a common reason for dental clinic visits, and understanding the role of oral microbiome is crucial for effective treatment strategies. Viewing the oral microbiota associated with halitosis from a broader ecological perspective can provide novel insights into oral and systemic health.
CRITICAL REVIEWS IN MICROBIOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Shruti Vidhawan Agarwalla, Kassapa Ellepola, Nikolaos Silikas, A. H. Castro Neto, Chaminda Jayampath Seneviratne, Vinicius Rosa
Summary: The study aimed to investigate the potential of graphene nanocoating to decrease long-term fungal biofilm development and hyphae growth on titanium. Results showed that graphene nanocoating exerted a persistent inhibitory effect on biofilm formation on titanium, reducing cell attachment and preventing mature biofilm formation.
Article
Dentistry, Oral Surgery & Medicine
Armelia Sari Widyarman, Nadeeka S. Udawatte, Citra Fragrantia Theodorea, Anie Apriani, Mario Richi, Tri Erri Astoeti, Chaminda Jayampath Seneviratne
Summary: The study showed that the CPP-ACP/F treatment modulated the dysbiotic oral microbiome towards a healthier state, increasing the abundance of certain microbial protective species. Although the overall community structure in children with caries was relatively uniform, there were significant differences in bacterial species before and after treatment. Three bacterial species were found to be strongly sensitive to the CPP-ACP/F treatment, indicating potential clinical significance of this varnish treatment in modulating the dental plaque microbiome.
JOURNAL OF DENTISTRY
(2021)
Article
Immunology
Sarah Sze Wah Wong, Lakshmi Prabha Venugopalan, Audrey Beaussart, Anupama Karnam, Mohammed Razeeth Shait Mohammed, Jeya Maheshwari Jayapal, Stephane Bretagne, Jagadeesh Bayry, Lalitha Prajna, Dharmalingam Kuppamuthu, Jean-Paul Latge, Vishukumar Aimanianda
Summary: This study compared conidia of Aspergillus fumigatus and Aspergillus flavus, revealing significant differences in immune response, protein content, and cell wall polysaccharide structure. These differences contribute to the species-specific infection establishment and varying sensitivities to antifungal drugs, proposing the efficacy of tailored treatment strategies for each species.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Preethi Balan, Yap Seng Chong, Qingsong Lin, Teck Kwang Lim, Tanujaa Suriyanarayanan, Nadeeka Shiyamalee Udawatte, Mun Loke Wong, Violeta Lopez, Hong-Gu He, Chaminda Jayampath Seneviratne
Summary: Through iTRAQ analysis and ELISA, the study found that neutrophil mediated immune response was overrepresented in all three trimesters of pregnancy, despite the decrease in phagocytic responses. Significantly higher Neutrophil Extracellular Traps (NETs) formation was observed in the third trimester of pregnancy, coinciding with the resolution of pregnancy gingivitis. Hormone-driven NETs formation may be the main defense mechanism contributing to the remission of pregnancy gingivitis.
IMMUNOLOGICAL INVESTIGATIONS
(2022)
Review
Dentistry, Oral Surgery & Medicine
Lakshman Perera Samaranayake, Chaminda Jayampath Seneviratne, Kausar Sadia Fakhruddin
Summary: The successful development of a vaccine against COVID-19 within a short period of time is a testament to human ingenuity, with vaccination being crucial for dental professionals as it may become a mandatory requirement in dental practice.
Article
Biochemical Research Methods
Preethi Balan, Yap Seng Chong, Lin Qingsong, Teck Kwang Lim, Mun Loke Wong, Violeta LOPEZ, Hong-Gu HE, Chaminda Jayampath Seneviratne
Summary: Early pregnancy loss (EPL) is a common complication in clinical practice, often misunderstood as a normal menstrual cycle. Research has found that the depletion of histone proteins in saliva can impact nucleosome assembly, potentially leading to pregnancy loss. Monitoring salivary histone levels could provide quick diagnostic information for treatment decisions in cases of threatened miscarriage.
PROTEOMICS CLINICAL APPLICATIONS
(2021)
Article
Dentistry, Oral Surgery & Medicine
V Rosa, R. Malhotra, S. Agarwalla, J. L. P. Morin, E. K. Luong-Van, Y. M. Han, R. J. J. Chew, C. J. Seneviratne, N. Silikas, K. S. Tan, C. A. Nijhuis, A. H. Castro Neto
Summary: The study demonstrates that graphene nanocoating (GN) deposited onto dental and orthopedic implants has antimicrobial properties and enhances bone formation, while also maintaining high integrity and quality under different stresses.
JOURNAL OF DENTAL RESEARCH
(2021)
Article
Microbiology
Laure Nicolas Annick Ries, Patricia Alves de Castro, Lilian Pereira Silva, Clara Valero, Thaila Fernanda dos Reis, Raquel Saborano, Iola F. Duarte, Gabriela Felix Persinoti, Jacob L. Steenwyk, Antonis Rokas, Fausto Almeida, Jonas Henrique Costa, Taicia Fill, Sarah Sze Wah Wong, Vishukumar Aimanianda, Fernando Jose Santos Rodrigues, Relber A. Goncales, Claudio Duarte-Oliveira, Agostinho Carvalho, Gustavo H. Goldman
Summary: Aspergillus fumigatus relies on host-specific carbon sources such as acetate during infection, with the transcription factor FacB playing a key role in acetate metabolism. The utilization of acetate is subject to carbon catabolite repression, affecting virulence traits and in vivo pathogenicity.
Letter
Dentistry, Oral Surgery & Medicine
E. Ng, J. R. H. Tay, N. H. L. Leung, C. J. Seneviratne
JOURNAL OF DENTAL RESEARCH
(2022)
Article
Chemistry, Physical
Xuan Li, Chuan Wang, Leilei Wang, Regina Huang, Wai-Chung Li, Xinna Wang, Sarah Sze Wah Wong, Zongwei Cai, Ken Cham-Fai Leung, Lijian Jin
Summary: This study demonstrates that a nanosystem with controlled-release and cell penetrating properties can effectively modulate immuno-inflammatory responses by inhibiting the NF-KB signaling pathway. It provides a novel approach for precision healthcare by targeting the NF-KB pathway to regulate innate host response.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Immunology
Rajashri Shende, Sarah Sze Wah Wong, Heikrujam Thoihen Meitei, Girdhari Lal, Taruna Madan, Vishukumar Aimanianda, Jayanta Kumar Pal, Arvind Sahu
Summary: Invasive aspergillosis is a life-threatening fungal infection for immunocompromised hosts. The study found that complement deficiency increases susceptibility to systemic infection by Aspergillus fumigatus.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Gaelle Lamona, Alons Lends, Isabel Valsecchi, Sarah Sze Wah Wong, Vincent Dupres, Frank Lafont, James Tolchard, Christine Schmitt, Adeline Mallet, Axelle Grelard, Estelle Morvan, Erick J. Dufourc, Birgit Habenstein, J. Inaki Guijarro, Vishukumar Aimanianda, Antoine Loquet
Summary: Through the use of magic-angle spinning NMR, researchers found that the cell wall polysaccharides of Aspergillus fumigatus undergo dynamic remodeling during conidial germination. They also discovered a significant change in the molar ratio of major polysaccharides after dormancy break, while the chitin content remained constant.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Pharmacology & Pharmacy
Karlie R. Sharma, Christine M. Colvis, Griffih P. Rodgers, Douglas M. Sheeley
Summary: There are many genes within the druggable genome that have not been studied, and the US National Institutes of Health's program provides resources to explore these genes, with the potential for rapid impact on human health.
DRUG DISCOVERY TODAY
(2024)
Review
Pharmacology & Pharmacy
Mohammad Sameer Khan, B. H. Jaswanth Gowda, Waleed H. Almalki, Tanuja Singh, Amirhossein Sahebkar, Prashant Kesharwani
Summary: Mitochondria-specific functional liposomes hold great potential for cancer therapy. This review discusses the association between mitochondria and tumor formation, as well as the advantages of liposomes in delivering drugs to mitochondria.
DRUG DISCOVERY TODAY
(2024)
Review
Pharmacology & Pharmacy
Choong Yong Ung, Cristina Correia, Hu Li, Christopher M. Adams, Jennifer J. Westendorf, Shizhen Zhu
Summary: With increasing human life expectancy, the global medical burden of chronic diseases is growing. Chronic diseases often involve malfunctioning of multiple organs, and understanding the interorgan crosstalk is crucial to understanding the etiology of chronic diseases. Researchers have proposed the locked-state model (LoSM) and cutting-edge systems biology and artificial intelligence strategies to decipher chronic multiorgan locked states. The findings have important clinical implications for improving treatments for chronic diseases.
DRUG DISCOVERY TODAY
(2024)
