Triazole-Resistance in Environmental Aspergillus fumigatus in Latin American and African Countries

Abstract

Triazole-resistance has been reported increasingly in Aspergillus fumigatus. An international expert team proposed to avoid triazole monotherapy for the initial treatment of invasive aspergillosis in regions with >10% environmental-resistance, but this prevalence is largely unknown for most American and African countries. Here, we screened 584 environmental samples (soil) from urban and rural locations in Mexico, Paraguay, and Peru in Latin America and Benin and Nigeria in Africa for triazole-resistant A. fumigatus. Samples were screened using triazole-containing agars and confirmed as triazole-resistant by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth dilution reference method. Isolates were further characterized by cyp51A sequencing and short-tandem repeat typing. Fungicide presence in samples was likewise determined. Among A. fumigatus positive samples, triazole-resistance was detected in 6.9% (7/102) of samples in Mexico, 8.3% (3/36) in Paraguay, 9.8% (6/61) in Peru, 2.2% (1/46) in Nigeria, and none in Benin. Cyp51A gene mutations were present in most of the triazole-resistant isolates (88%; 15/17). The environmentally-associated mutations TR34/L98H and TR46/Y121F/T289A were prevalent in Mexico and Peru, and isolates harboring these mutations were closely related. For the first time, triazole-resistant A. fumigatus was found in environmental samples in Mexico, Paraguay, Peru, and Nigeria with a prevalence of 7–10% in the Latin American countries. Our findings emphasize the need to establish triazole-resistance surveillance programs in these countries.

Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond

“…Coincidentally, the first resistant clinical isolate carrying TR 34 /L98H was reported infecting a patient in 1998 [ 14 , 30 ], just a few years after triazole fungicides had been introduced into the Netherlands [ 30 ], which suggests that this mutant could had emerged after azole fungicide contact in the field. Eventually, the TR 34 /L98H mutation was identified in many other European countries, and also in Asia, North and South America, Australia, and Africa [ 25 , 43 ].…”

Selection and Amplification of Fungicide Resistance in Aspergillus fumigatus in Relation to DMI Fungicide Use in Agronomic Settings: Hotspots versus Coldspots

“…High frequencies of ARAf have been detected in urban planted areas, for example, in the air above parks, in botanical gardens and other flowerbed soils, and flowerpot soil from urban locations (Supplementary Table S1). With some exceptions (e.g., [83]), these detection frequencies have also exceeded those for agricultural soils [35,60,84]. Given that DMIs are not applied as intensively in urban settings as in agronomic settings, it is conceivable that plant waste (presumably in the form of compost) from agricultural produce consumed in urban centres creates a local context for the amplification of ARAf, especially if it carries DMI residues (as suggested by Duong et al [40]), or that previously-composted materials transfer ARAf to urban settings.…”

“…Sewell et al [35] found the highest incidence of ARAf, with the greatest genotypic diversity, in soils from the urban environment of central London, rather than in samples from farmland, woodland, and pasture. A study of soil samples taken in five countries in South America and Africa [84] showed that ARAf was more prevalent in samples from urban sites than in those from agricultural land: mutants including TR 34 /L98H and TR 46 /Y121F/T289A were found in DMI-contaminated agricultural soils (in Peru), but also in urban flower bed soils lacking DMI residues (in Mexico and Paraguay). Tangwattanachuleeporn et al [85] did not recover ARAf isolates from soil sampled in metropolitan areas of Thailand, but they found resistant isolates in only ca.…”

“…Schoustra et al [5] showed that once the breakdown of plant material is complete, the resulting compost is low in A. fumigatus CFUs, and some studies have failed to detect ARAf in commercial compost samples [88,94,109]. However, the exclusion of A. fumigatus probably depends on how the compost is processed, as both wild-type and ARAf genotypes have been detected in samples of end-product commercial compost in several countries [32,53,84,101]. Shelton et al [77] tested garden soils from the UK and recovered more CFUs of ARAf (and more A. fumigatus CFUs generally) from samples containing compost (either commercial or home-made) than from those that did not.…”

Azole‐resistant Aspergillus fumigatus as an emerging worldwide pathogen

“…53 In addition, azole-resistant and azole-susceptible A. fumigatus strains harboring non-synonymous mutations F46Y, M172V, N248T, D255E, and E427K in the cyp51A gene have been isolated repeatedly from environmental and clinical samples throughout the world. [54][55][56][57] These amino acid substitutions have been shown to be located in the peripheral regions of the CYP51A protein, without interfering in the access channels for the binding of the azole compounds. 58 Therefore, the five mutations are regarded as polymorphisms of the cyp51A gene.…”