Fungal superbugs

1. FUNGAL
SUPERBUGS
W.P.S. Dilshan
AS2016053
Department of Botany
University of Sri Jayawardhanapura

2. CONTENT
Introduction
Resistance development depends factors
Mechanisms of fungicides resistance
Examples
Candida auris
Characteristics features
Isolation
How spread
Distribution
Plant pathogenic fungal superbugs
Treatments for fungal superbugs
Ongoing researchers
References
Who are infected
Symptoms
Identification
Treatment methods

3. Who are superbugs
"Superbugs" is a term used to describe
microorganisms that are resistant to the
majority of antibiotics commonly used today
and they are formed when antibiotics are used
regularly.
(Dr. James Steckelberg is a consultant in the Division of Infectious Diseases and a professor of
medicine at Mayo Medical School.)

4. Fungal superbugs
Fungi that are resistant to the majority of
antibiotics/fungicides commonly used today
when they use regularly.
Development of resistance to various
antifungals has been observed in sensitive
isolates.

5. •Fungicides resistance development depends on several
factors, in particular,
• the chemistry and mode of action of the fungicidal
compound,
• the frequency of use of the fungicide,
• the biology and reproductive ability of the target fungus,
• Mutations form in the fungus.

6. Mechanisms of fungicide resistance
1. Altered target site.
A fungicide has a specific target site where it acts to
disrupt a particular biochemical process or function.
If this target site is somewhat altered, the fungicide no
longer binds to the site of action and is unable to exert its
toxic effect.
This is the most common mechanism that fungi use to
become resistant.

7.  Fungicide A interferes with carbohydrate
metabolism by filling the target site of
Enzyme A.
 In resistant fungi, a part of the site is
altered preventing the fungicide from
fitting, but allowing carbohydrate
metabolism to occur.
 Enzyme A is necessary for carbohydrate
metabolism in fungi. The target site is the
point where the enzyme is used.

8. 2.Detoxification or metabolism.
Metabolism within the fungal cell is one mechanism.
A fungus with the ability to quickly degrade a fungicide, can
potentially inactivate it, before reach to its site of action.
Figure ; 01
Fungal cell

9. 3.Removal.
A fungal cell may rapidly export the fungicide before it can
reach the target site of action.
Figure ; 02
Fungal cell

10. 4.Reduced uptake of fungicide.
The resistant pathogen simply absorbs the fungicide
much more slowly than the susceptible type.
Figure ; 03
Fungal cell

11. Examples for fungal superbugs
•Candida auris
•Candida tropicalis
•Candida glabrata
•Aspergillus fumigatus

12. •Deadly fungus for human
•Often drug resistance
•Difficult to identify
Candida auris

13. Fig. 4. Candida auris JCM15448T. Vegetative
cells grown in glucose yeast extract-peptone
broth at 25 ◦C. Scale bar indicates 10 μm.
Kingdom; Fungi
Phylum; Ascomycota
Class; Saccharomycetes
Order; Saccharomycetales
Family; Saccharomycetidae
Genus; Candida
Species; Candida auris
It is a yeast.
Candida auris

14. Characteristic features.
That normally lives harmlessly on the skin and mucous membranes, according to
the Centers for Disease Control and Prevention (CDC) in United States.
The yeast was first discovered in 2009 from the ear discharge of a patient in
Japan, though a retrospective study of old medical samples found one infection
dating back to 1996 in South Korea.
Almost all tested isolates are resistant to fluconazole, an important first-line
antifungal agent.
In a recent global study, more than 40% of isolates were resistant to two or more
major classes of antifungals.(Erika Britza and Nelesh P Govender 2016)
Candida auris

15. • C. auris possesses virulence factors, such as
• germination,
• adherence,
• formation of biofilms,-
adherent biofilm communities on a range of clinically important substrates.
C. auris to form antifungal-resistant biofilms against all three main classes
of antifungals.
• production of phospholipases and proteinases.
Candida auris

16. Isolation
From a range of infected body sites, including
Skin (very common),
Urogenital tract (common),
Respiratory tract (occasional),
From blood cultures.( About 54% of recognized U.S. clinical cases have been identified)
Skin wounds,
Bile fluid,
Ears.
From fomites in hospitals such as
Blood pressure cuffs,
Stethoscopes,
On settle plates around patient bedsides,
On monitoring devices (within the UK),
Other equipment in contact with the patient.
(Public Health England 2016 June and CDC in US)
Candida auris
 Able to survive on dry
plastic on hospitals.
 Growth in vitamin-free
medium is positive.

17. How spread
Researchers have hypothesised that, it contaminate the immediate
environment of infected or colonised patients with onward
transmission,
ofrom the hands of healthcare workers,
ofrom fomites.
From contaminated environments (public health England 2016)
Candida auris

18. How spread……
From person to person within hospitals and
clinics/Nosocomial transmission
(Stephanie Pappas, Live Science Contributor | April 8, 2019 )
Patients have been persistently colonized with C. auris,
posing long-term risk of transmission.
Close contacts of patients, such as roommates and ward mates,
can develop asymptomatic colonization, which puts them at
risk for invasive infections, and these colonized patients can, in
turn, serve as a source of transmission to others.
Candida auris

19. Distribution
Candida auris
4
 United state
 South Africa
 United Kingdom
 India
 Pakistan
 Venezuela
 Spain
 Israel
 Colombia
 Japan
Sri Lanka is at a risk

20. Who get infected
 People who had weakened immune system
 Long term health care facilities residence
The presence of a central venous catheter (CVC)
Urinary catheter
IV lines
Persons in ICUs
New borns
 People who take immune system suppressive drugs for metabolisms, who
have diabetes.
 Over use of drugs
 Those requiring chemotherapy, antibiotic therapy.
 Chronic kidney disease
Candida auris

21. Symptoms
• Fever
• Chills
• Aches
• Fatigue
and
The disease can be fatal
Candida auris

22. Identification
• Phenotypically, C. auris is difficult to distinguish from other
pathogenic Candida species.
• Antifungal susceptibility testing
There are no established minimum inhibitory concentration (MIC)
breakpoints at present for C. auris.
• C. auris is frequently misidentified in the routine diagnostic
laboratory using commercially-available biochemical methods.
• Genome sequencing of the organism is the best method.
Candida auris

23. Prevention methods
Candida auris
Identify colonized
patients and isolate
them
Hand hygiene
Daily and terminal
cleaning using
disinfectants
Ultraviolet light
Avoid transmission
directly from
fomites
Waste and linen
disposal

24. C. auris is able to survive on a wide range of dry and moist
surfaces, including plastic where the pathogen may reside for up to
14 days.
C. auris seems to be resistant to quaternary compounds,
disinfectants and cationic surface-active products.
The CDC first issued an alert about drug-resistant C. auris in 2016
and today describes it as a "serious threat.“
Nearly half of patients who contracted fungus died
within 90 days.
Candida auris

25. Candida aurius
They are genetically distinct on different continents, suggesting
that the drug resistance is evolving separately but simultaneously
worldwide.
It's unclear what is causing this rise in these fungal "superbugs,“
but one theory is that widespread fungicide use on crops is
prompting C. auris to evolve resistance.

26. Plant pathogenic fungi which are highly resistance
to the antifungals.
• Grey mould fungus Botrytis cinerea
• Wheat pathogen Mycosphaerella graminicola
• Citrus pathogen Penicillium digitatum
• Apple scab fungus Venturia inaequalis

27. Treatments for fungal superbugs
1. Returning to the ‘pre-antibiotic era’.
Ancient remedies, including essential oils and their components as a
source of new antimicrobials.
In antiquity, medicinal oils were used as a mixture.
2. Combination of existing drugs with essential oils and/or
components.

28. 3. Crop management,
such as
Limitation of nitrogen fertilizer,
Reduction of the humidity
Removal of infected fruits and plant parts
Crop rotation.
Treatments for fungal superbugs…….

29. 4. Biological control
by
using non-synthetic compounds with antifungal or plant resistance
inducing activity,
or
antagonistic microorganisms (biofungicides).
Examples for products which are marketed are resistance-inducing
extracts containing
β-laminarin, or bacteria (e.g. Bacillus spp.),
yeasts (e.g. Candida oleophila, Aureobasidium pullulans) and
filamentous fungi (e.g. Trichoderma harzianum).
These products, in particular, the biofungicides, often work well in
controlled environments but are still unreliable in open-field cultures.
Treatments for fungal superbugs………

30. •Superbugs act against multiple drugs,
disinfectants and difficult to control.
•Thus antifungal resistance is currently
outpacing research and development to find
new drugs.
Humanity is facing a return to the ‘pre-
antibiotic era’.

31. References:
1. Cdc.gov. (2017). [online] Available at: https://www.cdc.gov/fungal/diseases/candidiasis/c-auris-alert-09-17.html
[Accessed 15 Jul. 2019].
2. Boire, N. (2013). Essential Oils and Future Antibiotics: New Weapons against Emerging‘Superbugs’?. Journal of
Ancient Diseases & Preventive Remedies, 01(02).
3. Britz, E. and Govender, N. (2016). Global emergence of a multi-drug resistant fungal pathogen,Candida
auris. Southern African Journal of Infectious Diseases, 31(3), pp.69-70.dc.gov. (2017). [online] Available at:
https://www.cdc.gov/fungal/diseases/candidiasis/c-auris-alert-09-17.html [Accessed 15 Jul. 2019].
4. Cortegiani, A., Misseri, G., Fasciana, T., Giammanco, A., Giarratano, A. and Chowdhary, A. (2018). Epidemiology,
clinical characteristics, resistance, and treatment of infections by Candida auris. Journal of Intensive Care, 6(1).
5. Hahn, M. (2014). The rising threat of fungicide resistance in plant pathogenic fungi: Botrytis as a case study.
6. Hps.scot.nhs.uk. (2017). HPS Website - Guidance for the laboratory investigation, management and infection
prevention and control for cases of Candida auris. [online] Available at: https://www.hps.scot.nhs.uk/web-resources-
container/guidance-for-the-laboratory-investigation-management-and-infection-prevention-and-control-for-cases-of-
candida-auris/ [Accessed 15 Jul. 2019].
7. Pesticidestewardship.org. (2019). Mechanisms of Fungicide Resistance – Pesticide Environmental Stewardship.
[online] Available at: https://pesticidestewardship.org/resistance/fungicide-resistance/mechanisms-of-fungicide-
resistance/ [Accessed 15 Jul. 2019].
8. Satoh, K., Makimura, K., Hasumi, Y., Nishiyama, Y., Uchida, K. and Yamaguchi, H. (2009). Candida aurissp. nov., a
novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiology
and Immunology, 53(1), pp.41-44.
9. Science, L. (2019). Deadly Fungal 'Superbug' Spreads Worldwide, Alarming Scientists. [online] Live Science.
Available at: https://www.livescience.com/65181-candida-auris-spreading.html [Accessed 15 Jul. 2019].
10. Xisto, M., Caramalho, R., Rocha, D., Ferreira-Pereira, A., Sartori, B., Barreto-Bergter, E., Junqueira, M., Lass-Flörl,
C. and Lackner, M. (2017). Pan-azole-resistantCandida tropicaliscarrying homozygouserg11mutations at position
K143R: a new emerging superbug?. Journal of Antimicrobial Chemotherapy, p.dkw558.

32. Thank you!