Nav: Home

Off-patent drug appears promising as broad-spectrum antifungal

October 31, 2018

Washington, DC - October 31, 2018 - By screening a library of off-patent drugs, scientists have identified a compound with promising broad-spectrum antifungal activity. The compound, alexidine dihydrochloride, warrants further development as a pan-fungal, anti-biofilm drug, according to the research reported in the journal mSphere.

"There are currently only three major classes of antifungal drugs used in the clinic and several pathogenic fungi are resistant to them, so there is an urgent need to identify compounds that have novel molecular targets," said principal study investigator Priya Uppuluri, PhD, assistant professor at Los Angeles Biomedical Research Institute at Harbor, University of California at Los Angeles (UCLA) Medical Center, Torrance, California. "Repurposing existing libraries of drugs that are approved for other indications can potentially be used for a new purpose as an antifungal. This can considerably shorten the drug discovery process."

Fungal pathogens are major drivers of morbidity and mortality, causing over 2 million infections and killing 1.5 million people per year, despite treatment with antifungal drugs. Invasive fungal infections due to Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans pose a substantial threat especially to hospitalized immunocompromised patients and others with compromised immune functions.

The severity of infections caused by these pathogens is accentuated due to their ability to develop a multicellular community of cells called "biofilms," on a wide variety of indwelling medical devices including central venous catheters (CVC). Once formed, biofilms serve as a reservoir of cells that have direct access into the vasculature, and cannot be eradicated due to their completely drug-resistant properties. Of concern, said Dr. Uppuluri, is that new strains of multidrug-resistant strains of fungi capable of forming biofilms, such as Candida auris, have emerged. The Centers of Disease Control and Prevention (CDC) has proclaimed C. auris as a serious global threat.

In the new study, researchers from LA Biomed at Harbor-UCLA screened the New Prestwick Chemical Library, a small molecule library of 1,200 FDA-approved, off-patent molecules, to identify compounds capable of simultaneously inhibiting growth of C. albicans, C. auris, and A. fumigatus. They further prioritized inhibitors for their potency against other fungal pathogens including C. auris and on their ability to kill preformed biofilms.

The researchers identified Alexidine dihydrochloride, a drug approved as a topical antimicrobial and anti-plaque agent, as the drug with the greatest antifungal and anti-biofilm activity against a diverse range of fungal pathogens. This compound significantly potentiated the efficacy of the clinically used azole drug fluconazole against biofilms, displayed low mammalian cell toxicity, and eradicated biofilms growing in mice central venous catheters, in vivo. Their findings highlight the drug's potential for use as a pan-antifungal drug.

"This is one of the first molecules identified that works as a pan-antifungal at very low concentrations, including against biofilms that are completely resistant to all drugs," said Dr. Uppuluri. The researchers are currently working on the medicinal chemistry aspect of synthesizing analogues of Alexidine dihydrochloride, to improve its physiochemical characteristics, and to reduce its toxicity to mammalian cells. Dr. Uppuluri encouraged other researchers to take advantage of the various drug libraries, many available at the Molecular Screening Shared Resources facility at UCLA, to screen molecules for their desired disease indications.
-end-
The American Society for Microbiology is the largest single life science society, composed of more than 30,000 scientists and health professionals. ASM's mission is to promote and advance the microbial sciences.

ASM advances the microbial sciences through conferences, publications, certifications and educational opportunities. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.

American Society for Microbiology

Related Pathogens Articles:

Inexpensive, portable detector identifies pathogens in minutes
Most viral test kits rely on labor- and time-intensive laboratory preparation and analysis techniques; for example, tests for the novel coronavirus can take days to detect the virus from nasal swabs.
Outsmarting pathogens
A new influenza strain appears each flu season, rendering past vaccines ineffective.
Autonomous microtrap for pathogens
Antibiotics are more efficient when they can act on their target directly at the site of infestation, without dilution.
Acidic environment could boost power of harmful pathogens
New findings published in PLOS Pathogens suggest lower pH in the digestive tract may make some bacterial pathogens even more dangerous.
On the trail of pathogens in meat, eggs and raw milk
To make food even safer for humans, experts from scientific institutions, food regulatory authorities and the business community will discuss current developments and strategies at the 'Zoonoses and Food Safety' Symposium at the German Federal Institute for Risk Assessment (BfR) on 4 and 5 November 2019, in Berlin-Marienfelde.
Protozoans and pathogens make for an infectious mix
The new observation that strains of V. cholerae can be expelled into the environment after being ingested by protozoa, and that these bacteria are then primed for colonisation and infection in humans, could help explain why cholera is so persistent in aquatic environments.
Your energy-efficient washing machine could be harboring pathogens
For the first time ever, investigators have identified a washing machine as a reservoir of multidrug-resistant pathogens.
Picky pathogens help non-native tree species invade
Trees have many natural enemies, including pathogens that have evolved to attack certain tree species.
How plague pathogens trick the immune system
Yersinia have spread fear and terror, especially in the past, but today they have still not been completely eradicated.
Metabolomic profiling of antibody response to periodontal pathogens
At the 97th General Session & Exhibition of the International Association for Dental Research (IADR), held in conjunction with the 48th Annual Meeting of the American Association for Dental Research (AADR) and the 43rd Annual Meeting of the Canadian Association for Dental Research (CADR), Jaakko Leskela, University of Helsinki, Finland, gave an oral presentation on 'Metabolomic Profiling of Antibody Response to Periodontal Pathogens.'
More Pathogens News and Pathogens Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.