Azole-resistant Aspergillus fumigatus harboring TR34/L98H, TR46/Y121F/T289A and TR53 mutations related to flower fields in Colombia

Abstract

Resistance to triazoles in Aspergillus fumigatus has been reported in azole-naive patients in Europe, Asia, Australia and North America. This resistance has been linked to fungicide-driven mutations in the cyp51A gene and its promoter region. We investigated the presence of environmental azole-resistant A. fumigatus strains related to the use of azole fungicides in Colombia. Soil samples were collected from flower beds, flower fields and public gardens from the outskirts, suburbs and city centre of Bogotá. Out of the 86 soil samples taken, 17 (19.8%) grew A. fumigatus of whom eight (9.3%) contained 40 strains able to grow on azole-containing itraconazole and/or voriconazole supplemented media. All but one triazole-resistant strains were isolated from soil samples collected from flower fields and flower beds (39/40). Importantly, the majority had the TR46/Y121F/T289A, TR34/L98H, and TR53 molecular resistance mechanisms and one azole resistant strain had a wild-type cyp51A gene. Soil samples from flower fields and beds contained 4 azole fungicides (penconazole, difenoconazole, tetraconazole and tebuconazole) above the limit of detection. Our findings underline the need for extensive investigations to determine azole-resistant A. fumigatus prevalence in both clinical and environmental samples in other regions of Latin America.

Emergence ofAspergillus fumigatusazole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes

“…Furthermore, the presence of ARAF isolates has also been increasingly reported in the environment in several European countries, in Asia and in South America, supporting the role of azole fungicides used in agriculture in the emergence of drug resistance . As most patients acquire A. fumigatus from the environment, the emergence and spread of azole‐resistant strains in the environment will put more humans at risk.…”

Emergence of azole resistant Aspergillus fumigatus and One Health: time to implement environmental stewardship

“…Even though most of the available fungicide compounds are exclusively designed for agricultural use (Brent and Hollomon, ), several belong to the same structural class as those used in human medicine with identical or very similar structures. These fungicides, with a similar structure as human azole antifungals, such as propiconazole, difenoconazole (in use since 1987 and 1993 respectively) and tebuconazole, bromuconazole and epoxiconazole (used since 1999) are particularly implicated in selection of azole resistance in A. fumigatus (Snelders et al ., ; Verweij et al ., ; Chowdhary et al ., ; Alvarez‐Moreno et al ., ;) and their usage coincide with the emerging increase of clinical azole resistant A. fumigatus (Meis et al ., ). The above‐mentioned five azole fungicides from the triazole class are highly active against wild‐type A. fumigatus , but show no activity against resistant isolates with TR 34 /L98H mutations (Chowdhary et al ., ).…”

Burden of Fungal Infections in Colombia

“…Finally, the estimations of both IA and CPA cases are greater than what is currently observed, probably related to the absence of a compulsory register of this disease, the absence of adequate diagnostic methods around the country (especially in areas with higher incidence of tuberculosis), and lack of clinical awareness, among other factors. The impacts of these invasive and chronic forms may worsen if one considers the recent description of azole-resistant Aspergillus fumigatus in the environment, which limits therapeutic options to intravenous therapy in most cases [61]. …”