Two new publications on Antifungal Surface Coatings

I’d like to highlight the great work from PhD student Javad Naderi.

Javad has published two papers on antifungal surface coatings.

The first, published in the Journal of Antimicrobial Chemotherapy, is on covalent coupling of two members of the echinocandin antifungal drug glass to surfaces. Both anidulafungin and micafungin surface coatings were highly antifungal vs Candida albicans.

Link to journal article. doi.org/10.1093/jac/dky437

Surface coatings with covalently attached anidulafungin and micafungin prevent Candida albicans biofilm formation. doi.org/10.1093/jac/dky437

However, perhaps the most important finding was that the anidulafungin surface killed yeast and prevented biofilm, and could be washed and rechallenged at least 5 times without losing efficacy.

This finding supports a mechanism of action where the drug is:

  • not eluted or cleaved from the surface
  • not affected by surface fouling

Along with previous publications on the other approved echinocandin, caspofungin, there is more evidence to suggest that the echinocandin drug class can be antifungal even when immobilised on surfaces (i.e. does not need diffusion to reach drug targets). Exactly how this happens is an active area or research for us.

The second explores the surface activity of another drug class, the polyenes. At first, it looks like drugs like amphotericin B remain active when attached to surfaces; however, if you are careful and you make sure to wash off ALL traces of loosely adsorbed compounds (leaving only contently attached) then this effect is eliminated.

Thus, not all surface coatings prepared using covalent attachment of antifungal drugs actually work.

Link to article: doi.org/10.1116/1.5050043

Surface-grafted antimicrobial drugs: Possible misinterpretation of mechanism of action. doi.org/10.1116/1.5050043

Failure to account for compounds that can be washed off and possible misinterpretation of mechanism of action should be an issue that researchers are made aware of.

This article was a Featured Article and a Scilight published in the journal Biointerphases.

 

 

The Fungus Olympics

Recently, Dr Sarah Kidd and I participated in the Fungus Olympics. This event is an international competition between laboratories to see how fungal strains use hyphae to navigate microscopic obstacles.

I wanted to share here my experience and fun I had participating in this event. Also, the event was important because we are able to learn much about how fungi sense surfaces: an important aspect of the way in which they cause diseases.

This has developed into an interesting story and I pitched the idea to The Conversation. I have been working on the article a great team there and the piece is nearing completion. Hopefully it will be soon when I can share the published final version.

Until then, I will tease a video from the event which is the first video that I’ve uploaded to YouTube. It shows one of our “athletes” navigating some of the microfluidic obstacles which make up the “events” in the competition.

Enterprising Research: a smarter way to use antibiotics to combat implant associated infections

Earlier this year, UniSA produced a video on our Research Themes Investment Scheme project. In this project we describe new materials that release antimicrobial compounds on demand.

Thomas, Hans, Pratiti and I had a lot of fun making this video. Here are some of behind the scenes photos from the production.

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Commuting with Curie. My top five audiobooks from 2017

In 2017, my daily commute (driving) increased from about 30 minutes to 90 minutes giving me the challenges of battling traffic, but also the opportunity to listen to audiobooks. The Libraries of South Australia allow users to borrow audiobooks. This has been a treasure trove of entertainment and learning, as I have devoured a banquet of excellent books, both fiction and non-fiction.

While I have listened to a number of biographies and fictions, I have particularly enjoyed non-fiction books on science. Below are my top five, starting at my #1 pick.

#1 The Age of Radiance: The Epic Rise and Dramatic Fall of the Atomic Era by Craig Nelson.

Product Details

This book gives the history of the discovery of radiation and presents a fascinating journey from Curie to Fukushima. The biographies are rich and enthralling. I was particularly captivated by the stories of the Curies, and their remarkable achievements. Also, the role of Lise Meitner was exceptionally well covered, marking her great achievements and showing how unjust it was in her not being awarded the nobel prize with Otto Hahn. The biography of Enrico Fermi was inspiring. Teller and Oppenheimer were beautifully compared and contrasted. The book ends in discussing the risks and benefits associated with the modern use nuclear power and wonders if we are too risk adverse, particularly when comparing human loss and suffering at the hands of both nuclear power and fossil fuels.

 

#2 Thinking Fast and Slow by Daniel Kahneman

Thinking, Fast and Slow by [Kahneman, Daniel]

Coming from a background in natural science, I was not aware of Nobel Prize winner Daniel Kahneman’s research in cognitive sciences. This book literally rewired my mind. Kahneman’s research elegantly shows the power of cognition and its wide implications into unconscious biases and decision-making. This book has genuinely caused me to reflect on my own cognitive biases and to understand the eponymous two agents (fast and slow) that influence my own decisions. I can say that I have implemented some of the described techniques into grant writing to present my ideas with more cognitive ease.

 

#3 AC/DC: The Savage Tale of the First Standards War by Tom McNichol

AC/DC: The Savage Tale of the First Standards War by [McNichol, Tom]

AC/DC is a history of the first standards war over electric current fought primarily between Edison and Westinghouse. There are many lessons here concerning basic scientific discoveries and how they are translated into products and services. Manipulation, deception, shoddy science and underhanded tricks were all part of the rivalry. Edison vehemently defended direct current as the future of electricity distribution and did everything in his power to show that AC was not just unsuitable, but deadly. In this endeavour, he vigorously promoted AC in the development of the electric chair to show just how dangerous it was, hoping to increase the adoption of DC. In the end, AC became the clear winner in the long distance transmission of electricity. However, author McNichol reminds us of the importance of DC in batteries and shows us that, not only is DC here to stay, but increased use in mobile devices and power storage means that the use of direct current has an important place in our future.

 

#4 A Brief History of Time by Stephen Hawking

I have always wanted to read this book and was glad to find it on audiobook. When originally released, this book became a classic and brought the strange word of astrophysics to popular culture. Nowadays, black holes, the big bang, and gravitational waves are all concepts that a prominent in society and we have Stephen Hawking’s bestseller to thank. I studied this book for its style in science communication and tried to peek in on the strategies that Hawking used to explain complex subjects simply. Besides being a fascinating look into contemporary astrophysics, the chapter describing Newton’s discoveries and approach to natural philosophy were completely fascinating and were presented exceptionally well.

 

#5 The Character of Physical Law by Richard Feynman

This book presents seven of Feynman’s lectures on physics. Each of the lectures covered material that I studied a long time ago as an undergraduate; however, I found Feynman’s lectures to be original and captivating. He is able to draw connections between physics and thermodynamics, quantum mechanics and gravitation, and brings together an enriching overview of the fundamentals. I secretly love thermodynamics and loved Feynman’s application of the second law to the distinction of the past and future.

 

The Importance of Fungal Pathogens and Antifungal Coatings in Medical Device Infections

How can we improve medical implants so that they combat microbial colonization and reduce the problem of implant-associated infections?

Basic science approaches for the design antimicrobial surfaces and coatings has been reviewed but it is clear that attention for fungal pathogens has been missing.

Fungal pathogens are important because they

  • Are misunderstood and underdiagnosed.
  • Severely affect immunocompromised and paediatric patients, and the elderly.
  • Are difficult to combat because antifungal agents tend to be toxic to human cells.

We have published a new review entitled The Importance of Fungal Pathogens and Antifungal Coatings in Medical Device Infections.

 https://www.sciencedirect.com/science/article/pii/S0734975017301520

The Importance of fungal pathogens and antifungal coatings in medical device infections

The review article is online now. Click the image to go to the website.

Highlights include:

  • Summary and evaluation of materials that release antifungal drugs and compounds.
  • Evaluation of the spectre of antimicrobial resistance (AMR) for fungi.
  • And provides critical discussion of the limitations in the field, with expert commentary on the future of the topic, as we see it, in the next five years, and then beyond.

This review is a significant addition to our 2014 review Biomaterials surfaces capable of resisting fungal attachment and biofilm formation. Biotech Adv. 2014; 32: 296-307.

This was a massive team effort that progressed over the course of one year. Our team of five authors wrote 17 pages of printed text and reviewed 89 references. This is the most comprehensive and up-to-date review in the field. We hope that the discussion on materials design will become an invaluable resource for researchers and feed into broader thinking about the wider field of design of antimicrobial biomaterials and polymicrobial biofilms.

Overview

Materials strategies for incorporating antifungals onto and into biomaterials.

Live cell imaging of Blumeria graminis germination on artificial surface coatings

The following video shows a time-lapse video of Blumeria graminis f.sp. hordei germination on an artificial surface coating conducted by Dr Bryan Coad and Dr Alan Little, University of Adelaide. The coating was made from hexacosanal (C26 aldehyde) mixed with Formvar ® resin and then cast onto glass slides using the previously published method (1).

Live cell imaging was conducted over 6 hours and compressed into a 5 second video. This video will automatically restart and loop.

In the first hour, primary germ tubes are extended and conidia “tilt” and roll slightly. A small proportion of the conidia develop appressorial germ tubes that extend away from the body. Some of these differentiate into hooked appresoria and attempt penetration of the surface coating. After 6 hours, low humidity in the chamber caused the conidia to desiccate.

This video is used to exemplify the method of live-cell imaging and visualisation of germination on artificial coatings. This technique can be used to visualise germination on other cuticle-mimetic surfaces (such as plasma cuticle mimics).

Using this method, we hope to understand (through visulisation) how fungal germ tubes are developed in response to surface chemistry and topography. Understanding the physicochemical features of surfaces will aid in the discovery of new agents to protect crops from diseases.

References

  1. Hansjakob, A.; Bischof, S.; Bringmann, G.; Riederer, M.; Hildebrandt, U. New Phytologist 2010, 188 (4), 1039-1054

Antifungal surfaces go 3D

We have continued our investigation on coatings that could be used to combat deadly fungal infections. Implanted medical devices can become colonised by the fungal yeast Candida albicans despite sterilisation procedures. Therefore, a medical device with a surface modification that could kill Candida on contact may help to reduce infection and death from these infections.

Previously we have shown that the antifungal drug caspofungin can be attached to medical-grade plastics using an ultra-thin surface layer only 20 nm thick. Because this coating is thin and flat, the caspofungin molecules essentially form a flat layer (approximately a 2 dimensional surface).

Our latest research has investigated the possibility of instead attaching caspofungin on polymer brushes. This allows the drug to be presented on flexible polymer linkers, extending hundreds of nanometres from the surface, and would improve the way the drug interacts with the fungal cell wall.

Depiction of the reaction steps, combining plasma polymerization and ARGET-ATRP to covalently attach amine-containing drugs, such as caspofungin, to surface-grafted PHEMA.

This is an important advancement in helping us to understand how surface-immobilised drugs interact with the fungal cell wall. We will use this information to understand how antibiotics work mecahanistically – that is, how tethered drugs would be able to penetrate into the cell wall and find their target of action which ends up killing the cell. Finding new mechanisms of action for antibiotic drugs could be one way that we can find new uses for a dwindling supply of effective antibiotic agents.

The work has been published in the journal Biointerphases and is an “Editor’s Pick”. This article is freely accessible through open access publishing.

We gratefully acknowledge the Australian Research Council for funding. (Discovery Project DP150101674. “Combating fungal biofilm growth on surfaces”.)

Australasian Society for Biomaterials and Tissue Engineering (ASBTE) conference 2017

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The Australasian Society for Biomaterials and Tissue Engineering Conference (ASBTE) was held in Canberra from 18th to 20th April, 2017.

The conference venue was ANU commons. It was perfect autumn weather.

Conference venue: ANU commons

Conference venue: ANU commons

Thomas, Steph and Javad all presented posters

Javad presenting his poster

Javad presenting his poster

Steph presenting her poster for absentee Carla

Steph presenting her poster for absentee Carla

Group photo: Javad, myself, Hans, Anouck, Thomas, and Steph

Group photo: Javad, myself, Hans, Anouck, Thomas, and Steph

 

The conference dinner was filled with wonderful food, and a 25th anniversary slide show for past ASBTE conferences.

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Hans was able to receive his Award of Excellence (officially awarded last year at the World Biomaterials Congress) and gave a moving speech about his years of research and its impact.

Hans Griesser receiving his ASBTE research excellence award

Hans Griesser receiving his ASBTE research excellence award

The conference was well attended right up to the last session.

ASBTE conference closing ceremony. Close to 200 delegates attended this years' conference.

ASBTE conference closing ceremony. Close to 200 delegates attended this years’ conference.

 

How to improve chemical functionality in deposited films

Our ARC Discovery Project (“Order from Chaos“) is aimed toward discovering how to improve polymer surface coatings — such as those that will be useful in advanced manufacturing of new materials. In the previous post, I discussed the discovery of how to make functional coatings from one chemical compound EBiB. Our latest published research describes a systematic investigation of three similar chemical compounds and is working towards establishing more general rules that could be applied more widely.

MIB EIB ETMA

Using structurally-related esters, lead author Solmaz Saboohi found the plasma deposition could proceed either through the α regime (lower pressure, collisional) or through the γ regime (higher pressure, collisionless). Analysis of the plasma phase and the deposited films showed noticeable differences under either conditions and markedly different coatings produced.

This discovery is helping us to understand the deposition characteristics of small molecular weight esters, which will hopefully be extended and generalised towards other compounds in the future.

Results have been recently published in the Royal Society of Chemistry journal Physical Chemistry Chemical Physics.

Link to article on publisher’s site.

Phys chem chem phys