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- Title
Emergence of azole resistance in Aspergillus fumigatus: a global problem.
- Authors
Liravizadeh, Siavash; Joodzadeh, Soroush; Zabeti, Erfan; Mohammadi, Ali; Pakzad, Sana; shafiee, Mahsa Shoja; Effati, Aylar; Nabili, Mojtaba
- Abstract
Introduction: Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis and causes one of the highest numbers of deaths among patients with fungal infections. Infections caused by A. fumigatus are a significant clinical issue and represent the second most-common form of fungal infection. Infections associated with azole-resistant A. fumigatus have a significantly-increased mortality in recent years. Materials and Methods: Data were collected by performing searches using a specified set of Medical Subject Heading (MeSH) terms like A. fumigatus, Azole, Resistance, TR34/L98H, TR46/Y121F in the following databases and search engines: MEDLINE, ISI Web of Science, Ebsco, Science Direct, Scopus, and Google Scholar. Result: The first azole resistance isolate was detected in 1997 in the U.S and azole resistance has been reported from many other countries too. A. fumigatus resistance to Azole drugs has been raised as a global problem. For this reason, in late 2000, the medical community was forced to consider these reports, it was also found that most cases of azole resistance disease are due to the environmental resistance of A. fumigatus. Azole Resistance in A. fumigatus can be Appearance in two ways: a Resistant that is generated during long clinical treatments and another Resistant caused by the environment due to the extensive use of demethylation inhibitors in agriculture (Multiple studies have now demonstrated TR34/L98H triazole resistance strains of A. fumigatus from soil.TR34/L98H is the predominant resistance mechanism of environmental origin in A. fumigatus). Since the first report of the A. fumigatus azole resistance strain, several studies have been published investigating the underlying molecular mechanisms. In A.fumigatus, the main targets of the azoles are Cyp51 proteins, encoded by two different, cyp51A and cyp51B. Tandem repeat sequence insertions at the cyp51A promoter consisted of overexpression and substitution. The integration of a 34-bp tandem repeat (TR34) with a substitution of leucine 98 to histidine (TR34/L98H) and a 46-bp tandem repeat insertion in the promoter region and substitutions of tyrosine 121 to phenylalanine and threonine 289 to alanine (TR46/Y121F/T289A) leading to an overexpression of cyp51A along which is related to VRC resistance also overexpression of the ATP-binding cassette (ABC) proteins transporter Cdr1B has been detected in recent years. Recent epidemiological data show that this mechanism is an expanding problem, with reports from China, Iran, and India. Triazole resistance rates of A.fumigatus isolates with integration in the cyp51A promoter by Belgium 5.7%, Denmark 4.5%, France 0.85%, Germany 3.2%, Portugal 0%, Spain 0.6%, UK 6.6%, Turkey 10.2%, China 5.5%, India 1.94%, Iran 3.3%, Japan 11.2%, Kuwait 12.5%, USA 0.55%, Australia 2.1% has been reported. Conclusion: Due to the increased resistance of this fungus to modern drugs, we need to use new drugs with new technologies, such as nano, that have better therapeutic effects. Using the new methods of incidence and prevalence A.fumigatus resistant to Azole in the future is expected.
- Subjects
IRAN; ASPERGILLUS; CONFERENCES &; conventions; DRUG resistance in microorganisms
- Publication
Current Medical Mycology, 2018, Vol 4, p172
- ISSN
2423-3439
- Publication type
Article
- DOI
10.18502/cmm.4.S1.2018.180