Emergence of Azole-Resistant Aspergillus fumigatus from Immunocompromised Hosts in India

Dabas, Y. P. S.; Xess, Immaculata; Bakshi, Satvinder Singh; Mahapatra, Manoranjan; Seth, Rachna

doi:10.1128/aac.02264-17

Cited by 19 publications

(18 citation statements)

References 59 publications

(57 reference statements)

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“…2016 , Wiederhold et al. 2016 , Dabas et al. 2018 , Tsuchido et al.…”

Section: The Worldwide Clinical Burden Of Arafmentioning

confidence: 99%

“…2006 , 2009 , Albarrag et al. 2011 , Dabas et al. 2018 ) 0.5–4 0.06–2 >8–16 ND ND ND ND ND China (2011–2014; 1), France (2006–2009; 1) G432A/S (2) ( Alanio et al.…”

Section: The Worldwide Clinical Burden Of Arafmentioning

confidence: 99%

“…2016 , Montesinos et al. 2017 , Dabas et al. 2018 , Denardi et al.…”

Section: The Worldwide Clinical Burden Of Arafmentioning

confidence: 99%

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Aspergillus fumigatusand aspergillosis: From basics to clinics

Arastehfar

Carvalho

Houbraken

et al. 2021

Studies in Mycology

141

112

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The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A . fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP 51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP 51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A . fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A . fumigatus . This review paper comprehensively discusses the current clinical challenges caused by A . fumigatus and provides insights on how to address them.

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“…2016 , Wiederhold et al. 2016 , Dabas et al. 2018 , Tsuchido et al.…”

Section: The Worldwide Clinical Burden Of Arafmentioning

confidence: 99%

“…2006 , 2009 , Albarrag et al. 2011 , Dabas et al. 2018 ) 0.5–4 0.06–2 >8–16 ND ND ND ND ND China (2011–2014; 1), France (2006–2009; 1) G432A/S (2) ( Alanio et al.…”

Section: The Worldwide Clinical Burden Of Arafmentioning

confidence: 99%

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Aspergillus fumigatusand aspergillosis: From basics to clinics

Arastehfar

Carvalho

Houbraken

et al. 2021

Studies in Mycology

141

112

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“…A previous homology model proved the interaction of P216L with POS but not with VRC, indicating that mutations in this region might play a role in POS resistance [ 49 ]. A. fumigatus strains with P216L mutation are resistant to itraconazole and posaconazole but not to voriconazole [ 50 , 51 ]. This peculiar azole susceptibility pattern is similar to the azole susceptibility phenotype exhibited by our A. flavus isolate which carries a P214L alteration.…”

Section: Discussionmentioning

confidence: 99%

Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus

Lúcio

González-Jiménez

Rivero-Menéndez

et al. 2020

Genes

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Infections caused by Aspergillus species are being increasingly reported. Aspergillus flavus is the second most common species within this genus causing invasive infections in humans, and isolates showing azole resistance have been recently described. A. flavus has three cyp51-related genes (cyp51A, cyp51B, and cyp51C) encoding 14-α sterol demethylase-like enzymes which are the target of azole drugs. In order to study triazole drug resistance in A. flavus, three strains showing reduced azole susceptibility and 17 azole susceptible isolates were compared. The three cyp51-related genes were amplified and sequenced. A comparison of the deduced Cyp51A, Cyp51B, and Cyp51C protein sequences with other protein sequences from orthologous genes in different filamentous fungi led to a protein identity that ranged from 50% to 80%. Cyp51A and Cyp51C presented several synonymous and non-synonymous point mutations among both susceptible and non-susceptible strains. However, two amino acid mutations were present only in two resistant isolates: one strain harbored a P214L substitution in Cyp51A, and another a H349R in Cyp51C that also showed an increase of cyp51A and cyp51C gene expression compared to the susceptible strain ATCC2004304. Isolates that showed reduced in vitro susceptibility to clinical azoles exhibited a different susceptibility profile to demethylation inhibitors (DMIs). Although P214L substitution might contribute to azole resistance, the role of H349R substitution together with changes in gene expression remains unclear.

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“…The centre studied the epidemiology of candidemia, azole resistant A. fumigatus, and molecular identification and resistance with Trichophyton species (Dabas et al, 2017;Dabas et al, 2018)…”

Section: All India Institute Of Medical Science New Delhimentioning

confidence: 99%

Mycology research in India in the last ten years (2008-2018)

Chakrabarti¹

2019

PINSA

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With the rise in the incidence of fungal infections in India due to the unique environmental and socioeconomic reasons, the research activities on fungal infections and fungi causing human infections have increased manifold. The major areas of clinical research on fungal infections include (i) epidemiology fungal infections, (ii) antifungal resistance detection, surveillance and its mechanism, (iii) molecular diagnosis and pathogenesis, (iv) outbreak investigations, (v) development of management guidelines, and (vi) clinical trials. The basic scientists' research areas include (i) understanding different molecular mechanisms on the evolution of fungi, (ii) computational models that is operating at different cellular levels of pathogenic fungi, (iii) understanding molecular details on the biosynthesis, signalling pathways involved in fungal virulence, (iv) identifying potential new antifungal drug targets, (v) basis of antifungal resistance mechanisms. The major centres in India carrying out advanced research in this field are Department of Medical Microbiology, PGIMER, Chandigarh, which also houses the National Reference Centre and WHO Collaborating Centre; Department of Pulmonary Medicine (PGIMER, Chandigarh), which focusses clinical research on respiratory mycoses; VP Chest Institute (New Delhi), JNCASR (Bengaluru), School of Life Science (JNU, New Delhi), CCMB (Hyderabad), and AIIMS (New Delhi). The two national organizations, Fungal Infection Study Forum (FISF) and Society for Indian Human and Animal Mycology (SIHAM) have conducted multicentric epidemiological studies. The fungal diseases that have been studied in India in the last decade include invasive candidiasis (due to Candida tropicalis, Candida glabrata, Candida albicans, Candida auris), mucormycosis (caused by Rhizopus arrhizus, Apophysomyces variabilis), invasive asperillosis (A. flavus and A. fumigatus), allergic bronchopulmonary aspergillosis (A. flavus and A. fumigatus), fungal rhinosinusitis (A. flavus), cryptococcosis (C. neoformans and C. gattii), histoplasmosis, sprorotrichosis, sebrohhoeic dermatitis/dandruff (Malassezia sp.), dermatophytosis (T. mentagrophytes, T. rubrum), mycetoma, fungal keratitis/endophthalmitis, phaeohyphomycosis (Cladophialophora bantiana).

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Emergence of Azole-Resistant Aspergillus fumigatus from Immunocompromised Hosts in India

Cited by 19 publications

References 59 publications

Aspergillus fumigatusand aspergillosis: From basics to clinics

Aspergillus fumigatusand aspergillosis: From basics to clinics

Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus

Mycology research in India in the last ten years (2008-2018)

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