April 2019
  Research highlight

Fungal derived lipopeptides - a review

This month’s research highlight is a review article which describes and discusses over 200 lipopeptide antibiotics derived from 30 species of fungi since 2000. The huge potential of these compounds as pharmaceutical drugs and/or biocontrol agents is discussed as well as a review of those which have been developed into commercial products or subjected to clinical trials, including cilofungin, caspofungin, micafungin, anidulafungin, rezafungin, emodepside, fusafungine and destruxins. Their sources, structural sequences, antibiotic activities (e.g. antibacterial, antifungal, antiviral,antimycobacterial, antimycoplasmal, antimalarial, antileishmanial, insecticidal, antitrypanosomal and nemati-cidal), structure-activity relationships, mechanisms of action, and specific relevance are discussed.
 
Fungi-derived lipopeptide antibiotics developed since 2000 (Zhao et al., 2019).
 
  News and notices
 
Don't forget the European Society for Paediatric Infectious Diseases (ESPID) in Ljubljana, Slovenia, from the 6th to the 11th of May, 2019.
 
Also coming up is the Fungal Pathogen Genomics course, running from the 7th to the 12th May 2019, this course will provide hands-on training in web-based data-mining resources for fungal genomes.
 
Antifungal stewardship: a new Massive Open Online Course (MOOC). Dr Riina Richardson (Consultant Clinical Mycologist, Department of Infectious Diseases and NHS Mycology Reference Centre Manchester, MFT and Senior Lecturer in Infectious Diseases, DIIRM) and Dr Stephen Hopping (Clinical Educational Fellow, Department of Infectious Diseases, MFT), both based at Wythenshawe Hospital have been commissioned by the British Society for Antimicrobial Chemotherapy (BSAC) to develop a MOOC consisting of interactive cases covering the key topics essential for a greater understanding of the importance and challenges of antifungal stewardship. The MOOC will launch in May 2019. More details available on the Future Learn platform.
 
The deadline to submit abstracts for the 9th Congress on Trends in Medical Mycology (TIMM-9) is fast appraoching! Don't miss out! Submit your abstract by 1st June 2019. The meeting will take place in Nice, France from the 11th to the 14th October 2019. 
 
  Research articles
 
Endotoxin and (1-3)-β-D-glucan contamination in electronic cigarette products sold in the United States (Lee et al., 2019)
Cigarette smoke contains microbes and microbial toxins, such as endotoxin and (1→3)-β-D-glucan, that may have adverse respiratory effects. To assess whether the same is true for e-cigarettes, the authors of this paper studied endotoxin and glucan levels from 37 cartridges and 38 e-liquid products from the top 10 bestselling brands in the US. They found that electronic cigarette products may be contaminated with microbial toxins. Endotoxin concentrations were over the limit of detection (LOD) in 23% of products tested, and glucan concentrations were greater than LOD in 81%.
 
This paper received a great deal of attention from the press and some associated articles are available below:
Proteomic characterization of Aspergillus fumigatus isolated from air and surfaces of the International Space Station (Blachowicz et al, 2019).
In this interesting paper the effects of the environment of the International Space Station (ISS) on microorganisms is investigated. The paper describes how low-nutrient availability, enhanced irradiation and microgravity may trigger changes in the molecular suite of microorganisms leading to increased virulence and resistance of microbes. Proteomic characterization of two Aspergillus fumigatus strains, ISSFT-021 and IF1SW-F4, isolated from HEPA filter debris and cupola surface of the ISS, respectively, is presented, along with a comparison to well-studied clinical isolates Af293 and CEA10. Proteins that showed increased abundance in ISS isolates were overall involved in stress responses, and carbohydrate and secondary metabolism.
 
Aspergillus terreus (Trichocomaceae): A natural, eco-friendly mycoinsecticide for control of malaria, filariasis, dengue vectors and its toxicity assessment against an aquatic model organism Artemia nauplii. (Ragavendran et al., 2018)
Vector-borne diseases like malaria, filariasis, and dengue are transmitted by mosquitoes and they cause global mortality and morbidity. This paper investigates Aspergillus terreus mycelia extract on different stages of mosquitoes such as egg, larvae, pupa, and adults in a variety of mosquito species. A. terreus extract exhibited strong neurobehavioral toxicity, knock-down effect (inability to fly or walk in a coordinated manner), ovicidal and adulticidal effect on Anopheles stephensi, Culex quinquefasciatus, and Aedes aegypti in a dose and time-dependent manner. The authors conclude that ethyl acetate extract of A. terreus contains promising mosquito control compounds and are working on isolating and identifying the bioactive constituents.
 
High airborne level of Aspergillus fumigatus and presence of azole-resistant TR34/L98H isolates in the home of a cystic fibrosis patient harbouring chronic colonisation with azole-resistant H285Y A. fumigatus. (Paluch et al., 2019).
This paper reports on the presence of an azole resistant A. fumigatus isolate in the home of an 18 year old cystic fibrosis patient who is chronically colonised with an H285Y CYP51A azole-resistant isolate. Whilst high levels of contamination were found, the environmental contaminating strain could not be found in the patient. The paper discusses the possible reasons for this and underlines the value of an environmental assessment to establish preventative measures and limit the risk of A. fumigatus exposure and subsequent azole-resistant A. fumigatus acquisition.
 
Targeting Aspergillus fumigatus Crf transglycosylases with neutralizing antibody is relevant but not sufficient to erase fungal burden in a neutropenic rat model. (Chauvin et al., 2019).
This study highlights the potential relevance of targeting chitin ring formation (CRF) cell wall protein (CWP) with therapeutic antibodies. To address the problem of antifungal toxicity, which is a particular problem for cystic fibrosis patients, the authors investigated the potential of CRF cell wall transglycosylases of A. fumigatus as targets for therapeutic antibodies as an alternative to conventional drugs. Anti-Crf antibodies neutralized the enzymatic activity of recombinant Crf protein, and delayed fungal growth by 12.3% in vitro when added to spores. In vivo, anti-Crf antibodies elicited a significant recruitment of neutrophils, macrophages and T CD4 lymphocytes but this was not correlated with a decrease of fungal burden in lungs and improvement in survival.
 
Baseline Chest Computed Tomography for Early Diagnosis of Invasive Pulmonary Aspergillosis in Hemato-oncological Patients- a Prospective Cohort Study. (Bitterman et al., 2019).
Invasive pulmonary aspergillosis (IPA) has dire consequences in hemato-oncological patients. This paper reports the authors’ experience with performing routine baseline chest computed tomography (CT) for early diagnosis of IPA. High rates of proven or probable IPA diagnosed on admission among patients with newly diagnosed acute myeloid leukemia (AML) were observed. This suggests that screening patients with newly diagnosed AML using a chest CT promotes early diagnosis of IPA and early initiation of targeted therapy.
 
 
  Veterinary articles
 
Labeled quantitative mass spectrometry to study the host response during aspergillosis in the common bottlenose dolphin (Tursiops truncatus) (Desoubeauz et al., 2019).
Expansion of the basic knowledge regarding the pathophysiology of aspergillosis in animals is critical to aid in the identification of new biomarkers of infection for diagnosis and therapeutic targets. In this study, a mass spectrometry analysis of proteins in blood collected from 32 Aspergillus infected common bottlenose dolphins in comparison with blood from 55 other dolphins (55 samples from 41 clinically-normal controls and from 14 cetaceans with miscellaneous non-Aspergillus inflammation diseases) and ten convalescent dolphins (28 samples). Sixty-six and 40 proteins were found to be ≥2.0-fold over- and underrepresented versus miscellaneous non-Aspergillus inflammatory dolphins, respectively, and most were confirmed vs. clinically-normal controls and convalescents. Many proteins which play a role in the adaptive immune response were identified, including MHC proteins and others involved in catalytic activity. The authors state that this technique should be considered as a preliminary step before validation of new diagnostic markers.
 
  Reviews
 
Molecular diagnostics in medical mycology (Wickes and Wiederhold, 2018).
Diagnosing fungal infections poses a number of unique problems, including a decline in expertise needed for identifying fungi, and a reduced number of instruments and assays specific for fungal identification compared to that of bacteria and viruses. These problems are exacerbated by the fact that patients with fungal infections are often immunosuppressed, which predisposes to infections from both commonly and rarely seen fungi. This review discusses current and future molecular technologies used for fungal identification, and some of the problems associated with development and implementation of these technologies in today's clinical microbiology laboratories.
 
Epidemiology of antifungal susceptibility: Review of literature (Hadrich and Ayadi, 2018).
Antifungal susceptibility testing methods are available to detect antifungal resistance and to determine the best treatment for a specific fungus. American and European standards have been developed, as well as equivalent commercial systems, which are more appropriate for clinical laboratories. These studies have allowed the development of interpretative breakpoints against the most frequent agents of fungal infections in the world. This review summarises the epidemiology of antifungal susceptibility pattern of different fungal species.
 
  Patients and carers
 
Medical Alert Cards
Medical alert cards (see left) for aspergillosis patients are now available in clinic or by emailing us at admin@aspergillus.org.uk
 
We recently participated in a webinar, hosted by NHS England and Rare Disease UK, on the subject of care coordination for rare diseases.
 
One topic of discussion was medical alert cards. NHS England is aiming to ensure that every patient with a rare disease has an ‘alert card’, including information about their condition, treatment regime and contact details for the individual expert involved in their care.
 
Rare Disease UK have requested feedback from us on how our medial alert cards are used. Please complete this survey and tell us your experiences so that we can be part of the discussion and help inform and influence policy on this important issue.
 
News mentions
This month two patients from the National Aspergillosis Centre, Sandra Hicks and Jean Jones, were interviewed by the Daily Mail and Sunday Times for articles about aspergillosis. Professor David Denning also contributed to the articles which can be read by following the links below. Please note that the Times article is behind a pay wall.
These articles were picked up and re-worked for the Express, Star and Mirror. A further article about Aspergillus in plant bulbs was also published just this week and features Professor Denning.
We estimate that the total readership of these publications is around 5 million so hopefully we reached a lot of people and raised awareness of aspergillosis!
 
Meetings and support
 
We host a weekly video phone call with around 4-8 patients and a member of NAC staff each week. You can use a computer or mobile device to join the video call by downloading the Zoom software by following this link: https://zoom.us/j/243782379. This meeting runs from 11:00-12:00 BST every Thursday.
 
To receive a text reminder when each meeting is approaching send us your mobile phone number (NB this doesn't operate in the US) to admin@aspergillus.org.uk.
 
Our meetings for the aspergillosis community occur on the first Friday of each month at the Altounyan Suite, North West Lung Centre, Manchester at 12.30pm BST. If you can't make it in person you are welcome to watch on Facebook. We broadcast live (this is limited to UK patients only) and post the recording so you can watch it in your own time. (Facebook Broadcast
 
Join our Facebook Groups
  • Our Aspergillosis Support Facebook Group has over 2000 members and is a safe place to meet and talk to other people with aspergillosis. We have a public group and a private group.
  • We also have a Facebook group for carers, friends and family of someone who is affected by the disease - join here
  • To find our regional and international groups, search the following terms within Facebook: 'aspergillosis'; 'aspergillus'; 'ABPA'
 
Jobs
Clinical networks
Conferences
 
 
 
 
2nd Antifungal Drug Discovery Symposium (9-10 May 2019 Duke University, North Carolina, USA)
 
NIAID - Fungi in Allergic Airway Disease (30-31 May 2019, Rockville, MD, USA)
 
Amercian Thoracic Society Conference (17-22 May 2019 Dallas, Texas, USA)
 
ASM Microbe (20-24 June 2019 San Francisco, California, USA)
 
Chest Regional Congress 2019 (27-29 June 2019 Athens, Greece)
 
3rd Aids-Related Mycoses Meeting (10-12 July 2019 Cape Town, South Africa)
 
Annual Meeting on Infectious Diseases (29-30 July 2019 Amsterdam, Netherlands)
 
See more groups and societies
 
 
Visit our sites
 
(MFIG)
(MRCM)
(free online microscopy course)
(fungal education for clinicians)
 
 

     
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR