Widespread amphotericin B-resistant strains of &lt;em&gt;Aspergillus fumigatus&lt;/em&gt; in Hamilton, Canada

Ashu, Eta Ebasi; Korfanty, Gregory A.; Samarasinghe, Himeshi; Pum, Nicole; You, Man; Yamamura, Deborah; Xu, Jianping

doi:10.2147/idr.s170952

Cited by 37 publications

(34 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To date, no resistance problems associated with echinocandins and amphotericin B have been identified in clinics. However, echinocandin-resistant mutants can be induced easily in vitro (630,631), and hot spots for point mutations inducing the resistance to amphotericin were identified in A. fumigatus after use of natamycin (632)(633)(634) and are starting to be seen in laboratories (635,636). However, resistance to AMB is only anecdotal.…”

Section: Antifungal Drugs and Therapy Antifungal Drugs And Associatedmentioning

confidence: 99%

Aspergillus fumigatus and Aspergillosis in 2019

2019

View full text Add to dashboard Cite

SUMMARY Aspergillus fumigatus is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of A. fumigatus; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against Aspergillus in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of A. fumigatus.

show abstract

Section: Antifungal Drugs and Therapy Antifungal Drugs And Associatedmentioning

confidence: 99%

Aspergillus fumigatus and Aspergillosis in 2019

2019

View full text Add to dashboard Cite

show abstract

“…Since its emergence in 1997, resistance to triazole in A. fumigatus has steadily increased and is a current global health menace [ 46 , 47 ]. Furthermore, in A. fumigatus, there are emerging reports of increased resistance to polyenes such as amphotericin B (AMB), an antifungal to which very little resistance has been reported thus far [ 48 , 49 ]. For example, a recent study carried out in Brazil showed that 27% of a clinical sample of A. fumigatus isolates was resistant to AMB (minimum inhibitory concentration (MIC) > 2 mg/L) [ 48 ].…”

Section: The Genus Aspergillusmentioning

confidence: 99%

Strengthening the One Health Agenda: The Role of Molecular Epidemiology in Aspergillus Threat Management

Ashu

2018

Genes

Self Cite

View full text Add to dashboard Cite

The United Nations’ One Health initiative advocates the collaboration of multiple sectors within the global and local health authorities toward the goal of better public health management outcomes. The emerging global health threat posed by Aspergillus species is an example of a management challenge that would benefit from the One Health approach. In this paper, we explore the potential role of molecular epidemiology in Aspergillus threat management and strengthening of the One Health initiative. Effective management of Aspergillus at a public health level requires the development of rapid and accurate diagnostic tools to not only identify the infecting pathogen to species level, but also to the level of individual genotype, including drug susceptibility patterns. While a variety of molecular methods have been developed for Aspergillus diagnosis, their use at below-species level in clinical settings has been very limited, especially in resource-poor countries and regions. Here we provide a framework for Aspergillus threat management and describe how molecular epidemiology and experimental evolution methods could be used for predicting resistance through drug exposure. Our analyses highlight the need for standardization of loci and methods used for molecular diagnostics, and surveillance across Aspergillus species and geographic regions. Such standardization will enable comparisons at national and global levels and through the One Health approach, strengthen Aspergillus threat management efforts.

show abstract

“…Interestingly the killing mode of antifungal drugs in C. elegans model was different from that in the in vitro culture. The macrolide polyene AmB is a well-known broad-spectrum fungicidal agent (Hamill, 2013 ; Ashu et al, 2018 ) while azole drugs, i.e., VoZ and ItrZ, are mainly fungistatic against A. fumigatus (Meletiadis et al, 2007 ). However, visible hyphal filamentation from a number of infected worms graduated to “ghost stage” under AmB treatment whereas only diffused internal hyphal growth and early germinated conidia were observed from worms treated with VoZ and ItrZ ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…The emergence of drug resistant strains to the wide range of currently available drugs has posed a serious challenge as cases are rising globally (Prigitano et al, 2017 , 2019 ; Abdolrasouli et al, 2018 ). Reports of A. fumigatus resistance to azole drugs (Hagiwara et al, 2017 ; Sharma et al, 2019 ), polyene drugs such as amphotericin B (Ashu et al, 2018 ), and echinocandin drugs (Beer et al, 2018 ) are increasing in both clinical (Prigitano et al, 2017 ; Abdolrasouli et al, 2018 ; Hagiwara et al, 2018 ) and environmental isolates (Vaezi et al, 2018 ; Prigitano et al, 2019 ). With the limited repertoire of antifungal drug classes, there is therefore the need to urgently discover new therapeutic option for this infection.…”

Section: Introductionmentioning

confidence: 99%

Caenorhabditis elegans-Based Aspergillus fumigatus Infection Model for Evaluating Pathogenicity and Drug Efficacy

Ahamefule

Qin

Odiba

et al. 2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Aspergillus fumigatus is the most reported causative pathogen associated with the increasing global incidences of aspergilloses, with the health of immunocompromised individuals mostly at risk. Monitoring the pathogenicity of A. fumigatus strains to identify virulence factors and evaluating the efficacy of potent active agents against this fungus in animal models are indispensable in current research effort. Caenorhabditis elegans has been successfully utilized as an infection model for bacterial and dimorphic fungal pathogens because of the advantages of being time-efficient, and less costly. However, application of this model to the filamentous fungus A. fumigatus is less investigated. In this study, we developed and optimized a stable and reliable C. elegans model for A. fumigatus infection, and demonstrated the infection process with a fluorescent strain. Virulence results of several mutant strains in our nematode model demonstrated high consistency with the already reported pathogenicity pattern in other models. Furthermore, this C. elegans-A. fumigatus infection model was optimized for evaluating the efficacy of current antifungal drugs. Interestingly, the azole drugs in nematode model prevented conidial germination to a higher extent than amphotericin B. Overall, our established C. elegans infection model for A. fumigatus has potential applications in pathogenicity evaluation, antifungal agents screening, drug efficacy evaluation as well as host-pathogen interaction studies.

show abstract

Widespread amphotericin B-resistant strains of <em>Aspergillus fumigatus</em> in Hamilton, Canada

Cited by 37 publications

References 26 publications

Aspergillus fumigatus and Aspergillosis in 2019

Aspergillus fumigatus and Aspergillosis in 2019

Strengthening the One Health Agenda: The Role of Molecular Epidemiology in Aspergillus Threat Management

Caenorhabditis elegans-Based Aspergillus fumigatus Infection Model for Evaluating Pathogenicity and Drug Efficacy

Contact Info

Product

Resources

About