Diagrammatic representation of similar structural binding mode of medical triazoles and triazole fungicides to <i>cyp</i>51A of wild-type <i>A. fumigatus</i>.

<p>(a) Dihalogenated phenyl group of triazoles forms van der Waals contact with the hydrophobic residues (encircled in red) of the active site (<i>cyp</i>51A), and the nitrogen atom of the five-membered aromatic ring of triazoles binds to the <i>cyp</i>51A heme moiety. In addition, the D-ring propionate (C₂H₅COO⁻) of the heme moeity forms hydrogen bonds with the side-chain hydroxyl group of triazoles. (b) Triazole fungicides show similar van der Waals contact at the hydrophobic pocket. However, the nitrogen atom of the five-membered aromatic ring of fungicide triazoles binds to the Ser297 residue at the active site. In addition, the triazoles tebuconazole and epoxiconazole are known to interact with the His296 residue while penconazole and metconazole form water-bridging interactions at the active site.</p

A global map depicting geographic distribution of multi-triazole-resistant clinical (red) and environmental (green) <i>Aspergillus fumigatus</i> strains carrying the TR₃₄/L98H (circle) and the TR₄₆/Y121F/T289A mutations (square).

<p>Countrywide prevalence rates (%) of <i>A. fumigatus</i> carrying TR₃₄/L98H are presented excepting the United Kingdom, where overall azole resistance is illustrated. The percent in parentheses denotes environmental prevalence rates.</p

Analysis of genotypic relationship between <i>A</i>. <i>terreus</i> isolates from India (n = 101), Europe (20), USA (20), Panama (n = 1), New Zealand (n = 1), Papua New Guinea (n = 2), China (n = 1), Taiwan (n = 1) and Thailand (n = 1) using STR typing.

<p>The dendrogram is based on a categorical analysis of 9 microsatellite markers in combination with UPGMA clustering. The scale bar indicates the percentage identity.</p

Minimum spanning tree showing wide genotypic diversity both in the clinical <i>A</i>. <i>terreus</i> isolates from India and those outside India.

<p>The figure shows the 115 different genotypes (circles), the number of strains belonging to the same genotype (sizes of the circles), and origin of isolates (circles in yellow indicate Indian isolates; green indicating European isolates including France (n = 4), Slovenia (n = 1), Germany (n = 2), Italy (n = 2), Norway (n = 2), Spain (n = 4), Netherlands (n = 5); pink indicate isolates from Australasia, including New Guinea (n = 2), New Zealand (n = 1), Taiwan (n = 1), China (n = 1), Thailand (n = 1); bright blue indicates isolate from Panama (Latin America; n = 1); dark blue indicates North American (n = 20) isolates). Gray-zone indicates microsatellite cluster representing minimal 2 isolates that differ maximum by 1 microsatellite marker out of 9. Thick and medium-thick branches indicate 1 or 2 microsatellite marker differences, respectively. Thick dashed line indicates 3 marker differences between two genotypes; 4 or more microsatellite markers differences between genotypes are indicated by medium thick and thin dashed lines, respectively.</p

Amplified fragment length polymorphism analysis showing genotypic diversity among 122 clinical and environmental Indian A. terreus isolates.

<p><i>Aspergillus terreus</i> (CBS 601.65^T), <i>A</i>. <i>terreus</i> var. <i>africanus</i> (syn. <i>A</i>. <i>neoafricanus</i> CBS 130.55^T), <i>A</i>. <i>terreus</i> var. <i>floccosus</i> (syn. <i>A</i>. <i>floccosus</i> CBS 116.37^T) were used for the analysis. The dendrogram was constructed by using UPGMA (unweighted pair group method with averages) in combination with the Pearson correlation coefficient and was restricted to fragments of 60–400 bp. Scale bar indicates the percentage similarity.</p

Phylogenetic tree based on partial sequence of <i>calmodulin</i> gene using maximum likelihood analysis depicting intraspecies variation among <i>A</i>. <i>terreus</i> isolates.

<p><i>Aspergillus terreus</i> (CBS 601.65^T), <i>Aspergillus alabamensis</i> (UAB38), <i>A</i>. <i>terreus</i> var. <i>africanus</i> (syn. <i>A</i>. <i>neoafricanus</i> CBS 130.55^T), <i>A</i>. <i>aureoterreus</i> (CBS 265.81^T), <i>A</i>. <i>hortai</i> (IBT16744, IBT16745 and IBT26384) of <i>A</i>. <i>terreus</i> section <i>Terrei</i> were taken as outliers for the analysis. Bootstrap values are shown above the branches. Environmental isolates are denoted by E, and clinical isolates are denoted by C.</p

Minimum spanning tree showing wide genotypic diversity in the TR₃₄/L98H and wild type <i>A. fumigatus</i> isolates studied.

<p>The figure shows the 74 different genotypes (circles), the number of strains belonging to the same genotype (sizes of the circles), and origin of isolates (circles in yellow indicate Indian isolates; green Dutch isolates; red Chinese isolates; blue French isolates, purple German isolate and white reference strain, AF293). Solid thick and thin branches indicates 1 or 2 microsatellite markers differences, respectively; dashed branches indicates 3 microsatellite markers difference between two genotypes; 4 or more microsatellite markers differences between genotypes are indicated with dotted branches.</p

Genotypic relationship between the wild-type and TR₃₄/L98H <i>Aspergillus fumigatus</i> (clinical and environmental isolates from India, The Netherlands and France) and TR₃₄/L98H <i>A. fumigatus</i> (clinical isolates from China and Germany).

<p>The dendrogram is based on a categorical analysis of 9 microsatellite markers in combination with UPGMA clustering. The scale bar indicates the percentage identity. Clinical: blue, Environmental: yellow, Resistant: red, Susceptible: green.</p

State-wise distribution of environmental <i>Aspergillus fumigatus</i> isolates with TR₃₄/L98H mutations from India.

*<p>Parenthesis denotes the numerator as number of samples positive for <i>A. fumigatus,</i> denominator denotes the number of samples tested; ^†UT, Union Territory; VPCI, V. P. Chest Institute; DU, Delhi University.</p

An outline map of India showing state-wise isolation of multiple-triazole resistant <i>Aspergillus fumigatus</i> isolates from variety of environmental samples.

<p>An outline map of India showing state-wise isolation of multiple-triazole resistant <i>Aspergillus fumigatus</i> isolates from variety of environmental samples.</p