PubMed HealthSearch

PubMed · 42462376

Triazole resistance in clinical Aspergillus fumigatus isolates in India, a multicenter surveillance study.

Abstract

BACKGROUND: Triazole resistance in Aspergillus fumigatus is a global public health concern associated with treatment failure, notably in invasive aspergillosis. However, population-level data on triazole resistance from India remain limited, with most reports originating from single-center studies. METHODS: We conducted a multicenter surveillance study to assess the prevalence of triazole resistance among clinical A. fumigatus isolates across India. Antifungal susceptibility testing was performed using the CLSI broth microdilution method (M38-Ed3), and molecular characterization was conducted on resistant isolates. A total of 518 isolates were analyzed: 115 prospectively collected from 13 tertiary-care hospitals from 2015-2020, and 403 archived isolates obtained from the National Culture Collection of Pathogenic Fungi (1994-2020). RESULTS: The overall pooled prevalence of non-wildtype isolates was 4.1% for itraconazole (95% CI: 2.54-6.17%), 3.9% for posaconazole (95% CI: 2.39-5.94%), while 1.4% were resistant to voriconazole (95% CI: 0.55-2.77%). One multi-azole-resistant isolate from an immunocompromised, mold-active triazole-na&#xef;ve patient carried the TR34/L98H mutation, suggesting environmental acquisition. Prevalence of resistance did not differ significantly across geographic regions or between public and private sector hospitals. Linear regression analysis revealed a significant temporal increase in median MICs of all three licensed triazoles between 1994 and 2020. Approximately 29% of isolates exhibited amphotericin B MICs exceeding the epidemiological cutoff value; however, the clinical significance of this finding remains uncertain. CONCLUSIONS: Azole resistance among clinical A. fumigatus isolates in India remains uncommon (<5%), supporting the continued use of triazoles as first-line therapy. However, the observed temporal increase in triazole MICs underscores the need for sustained national surveillance to detect emerging resistance trends.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Raees A Paul, Shivaprakash M Rudramurthy, Inderpaul S Sehgal, Umabala Pamidimukkala, Ranganathan N Iyer, Malini Capoor, Bansidhar Tarai, Anjali Shetty, Sanjay Bhattachharya, Jayanthi Savio, Shamsul Karim, Peralam Y Prakash, Immaculata Xess, Ujjwayini Ray, Anupma J Kindo, Rakesh Singh, Dipti Sharma, Kamini Walia, Harsimran Kaur, Anup Ghosh, Valliappan Muthu, Ritesh Agarwal, Rajeev Soman, Arunaloke Chakrabarti. 2026-07-08. Triazole resistance in clinical Aspergillus fumigatus isolates in India, a multicenter surveillance study.. https://doi.org/10.1016/j.diagmicrobio.2026.117541

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Functional characterization of SHC-like triterpene cyclase genes in azole response and virulence-related traits of Aspergillus fumigatus.

Aspergillus fumigatus is a major opportunistic fungal pathogen, and increasing azole resistance poses a challenge for aspergillosis treatment. Squalene is an upstream precursor of ergosterol biosynthesis and may also be utilized by SHC-like triterpene cyclases, suggesting a potential link between squalene-associated metabolism, membrane adaptation, and azole response. However, the roles of SHC-like triterpene cyclase genes in A. fumigatus remain unclear. Here, we characterized three candidates, shc1, shc2, and shc3, using comparative bioinformatic analysis, gene deletion, phenotypic assays, azole susceptibility testing, transcriptomics, and host-interaction models. Sequence, genomic-context, phylogenetic, and structural analyses suggested divergence among the three candidates. Individual shc deletion caused limited effects on vegetative growth, whereas loss of shc1 mildly reduced susceptibility to voriconazole and posaconazole, as reflected by twofold MIC increases and lower inhibition rates. Transcriptomic analysis revealed distinct remodeling patterns, with &#x394;shc3 showing the broadest transcriptional changes despite no detectable MIC shift. Targeted metabolite profiling and PI uptake analysis further supported an association between shc deletion, sterol/hopane-type triterpenoid balance, and membrane-associated properties. shc deletion also altered epithelial cell interaction phenotypes, while &#x394;shc1 showed reduced lethality in Galleria mellonella. In clinical isolates, elevated shc transcription was associated with azole-resistant backgrounds. These findings suggest functional diversification among SHC-like triterpene cyclase genes and indicate that shc1 may contribute to azole-associated adaptation and virulence-related traits in A. fumigatus.

Aspergillus fumigatus

Identification and characterization of non-canonical azole antifungal resistance pathways in Aspergillus fumigatus.

UNLABELLED: Human fungal infections, especially those caused by Aspergillus fumigatus, pose a significant global health threat, particularly in immunocompromised individuals. Azole antifungals are the primary treatment for this pathogen; however, the prevalence of azole-resistant A. fumigatus strains is steadily increasing. Mutations in cyp51A, which encodes an enzyme involved in ergosterol biosynthesis and the molecular target of the azoles, are well established to confer resistance in this fungal species. However, additional mechanisms governing resistance to this antifungal class remain understudied and poorly characterized, despite growing recognition of their importance in clinical resistance. In this study, we investigated the genetic basis of azole resistance in A. fumigatus isolates from clinical settings worldwide, with a particular focus on mechanisms independent of cyp51A (non-canonical). Using a combination of genomic and functional approaches, including whole-genome sequencing and transcriptomic analysis, we identified novel genetic variants and characterized population structure, advancing our understanding of the genetic diversity and evolutionary dynamics of resistance in A. fumigatus. By expanding our understanding of the complex genetic and molecular factors underlying azole resistance in this important human fungal pathogen, this research is poised to inform the development of novel antifungal strategies and contribute to global efforts to combat fungal infections. IMPORTANCE: Azole antifungals are the frontline therapy for infections caused by the opportunistic mold Aspergillus fumigatus, yet resistance to these drugs is rapidly increasing worldwide. Most studies have focused on mutations in cyp51A, the canonical target of azoles; however, a growing proportion of resistant clinical isolates lack these mutations, indicating that alternative resistance mechanisms are emerging. Here, we integrate population genomics, transcriptomics, and functional analyses across a global collection of isolates to define the architecture of cyp51-independent (non-canonical) azole resistance. We show that this resistance phenotype is strongly associated with a distinct population lineage and is driven by a highly polygenic network of metabolic, mitochondrial, and regulatory adaptations rather than single target site mutations. These isolates exhibit extensive transcriptional rewiring and metabolic remodeling under azole stress, suggesting distinct survival strategies beyond canonical resistance. Our findings reveal that azole resistance in A. fumigatus can evolve through diverse evolutionary routes and emphasize the need to monitor and therapeutically target non-canonical pathways that may increasingly contribute to antifungal treatment failure.

Aspergillus fumigatus

Detection of TR34/L98H pan-azole-resistant Aspergillus fumigatus in poultry farm environments.

INTRODUCTION: Poultry farms have been recognized as environments prone to fungal contamination. However, the occurrence of azole-resistant Aspergillus fumigatus and its cytotoxic potential remain insufficiently characterized. This study aimed to characterize the occurrence, cytotoxic potential, and azole-resistance profile ofAspergillus section Fumigati in poultry farms. METHODS: A total of 420 samples, including air (n = 47), electrostatic dust cloths (n&#xa0;= 87), bedding (n = 87), feed (n = 95), swabs (n = 87), workers' masks (n = 2), and broiler breast (n = 15), were obtained. Fungal characterization was performed through culture-based methods (27 &#xb0;C and 37 &#xb0;C), followed by azole resistance screening according to EUCAST guidelines. Resistant isolates were subjected to whole-genome sequencing and a targeted analysis of cyp51A mutations. The cytotoxicity potential of fungal isolates and environmental samples was evaluated using selected cell lines representing respiratory organs (human alveolar [A549]) and detoxification organs (swinekidney [SK]/hepatocellular carcinoma [HepG2]). RESULTS: Seven putative Aspergillus fumigatus isolates exhibited pan-azole resistance (MICs: &#x2265; 2 mg/L ITR/VOR; &#x2265; 1mg/L for POS). Four isolates carried the TR34/L98H mutation and were recovered from bedding (n = 3) and air (n = 1), suggesting the presence of resistant A. fumigatus in poultry farm matrices. Although 12% of isolates induced toxicity on both cell lines (17/145), no significant association was observed between isolate cytotoxicity and environmental sample toxicity, suggesting that additional biological and chemical components may contribute to the overall toxicological profile of farm environments. DISCUSION: The study highlights the occurrence of azole-resistant A. fumigatus in poultry farms and support integrated surveillance approaches addressing antifungal resistance and environmental exposure risks in poultry production.

Aspergillus fumigatus