Phylogeography and evolutionary patterns in Sporothrix spanning more than 14 000 human and animal case reports

Abstract

Pathology to vertebrate hosts has emerged repeatedly in the order Ophiostomatales. Occasional infections have been observed in Sporothrix mexicana at a low level of virulence, while the main pathogenic species cluster in a derived clade around S. schenckii s.str. In this paper, phylogeny and epidemiology of the members of this clade were investigated for 99 clinical and 36 environmental strains using four genetic loci, viz. rDNA ITS and partial CAL, TEF1, and TEF3; data are compared with amplified fragment length polymorphism (AFLP) genotyping. The four main species of the pathogenic clade were recognised. The species proved to show high degrees of endemicity, which enabled interpretation of literature data where live material or genetic information is lacking. The clade of four species comprised nine subclusters, which often had limited geographic distribution and were separate from each other in all partitions, suggesting low degrees of interbreeding between populations. In contrast, S. globosa exhibited consistent global distribution of identical AFLP types, suggesting another type of dispersal. Sporothrix brasiliensis is known to be involved in an expanding zoonosis and transmitted by cats, whereas S. globosa infections originated from putrid plant material, causing a sapronosis. Sporothrix schenckii s.str., the most variable species within the clade, also had a plant origin, with ecological similarities to that of S. globosa. A hypothesis was put forward that highly specific conditions in the plant material are required to promote the growth of Sporothrix. Fermented, self-heated plant debris may stimulate the thermodependent yeast-like invasive form of the fungus, which facilitates repeated infection of mammals.

Keywords: Sporothrix; epidemiology; historical biogeography; phylogeny; sapronosis; sporotrichosis; transmission routes; yeast conversion; zoonosis.

Fig. 1

Geographic distribution of sporotrichosis caused by S. brasiliensis, S. schenckii, and S. globosa according to case reports published over 70 years, compared with sequenced isolates and with expression of statistical probabilities that the prevalent endemic species was concerned in historical publications without sequence data. Samples were categorised as sequenced and non-sequenced specimens. The sizes of circumferences are roughly proportional to the numbers of cases / strains included. Numbers reported within the pies denote the number of strains examined. Main endemic areas indicated by dotted lines.

Fig. 1

Geographic distribution of sporotrichosis caused by S. brasiliensis, S. schenckii, and S. globosa according to case reports published over 70 years, compared with sequenced isolates and with expression of statistical probabilities that the prevalent endemic species was concerned in historical publications without sequence data. Samples were categorised as sequenced and non-sequenced specimens. The sizes of circumferences are roughly proportional to the numbers of cases / strains included. Numbers reported within the pies denote the number of strains examined. Main endemic areas indicated by dotted lines.

Fig. 2

Phylogenetic relationships inferred from PhyML based on ITS sequences of 101 strains belonging to Sporothrix and Ophiostoma. The numbers close to the branches represent indices of support (ML/NJ/MP) based on 1 000 bootstrap replications. Branches with bootstrap support value higher than 80 % are indicated in bold.

Fig. 2

Phylogenetic relationships inferred from PhyML based on ITS sequences of 101 strains belonging to Sporothrix and Ophiostoma. The numbers close to the branches represent indices of support (ML/NJ/MP) based on 1 000 bootstrap replications. Branches with bootstrap support value higher than 80 % are indicated in bold.

Fig. 3

Phylogenetic relationship inferred from Bayesian statistics based on concatenated CAL, TEF1 and TEF3 sequences of 135 strains of Sporothrix species. Bootstrap and posterior probabilities values were added to respective branches (BI/ML/NJ). Branches with bootstrap support values higher than 80 % are indicated in bold.

Fig. 3

Phylogenetic relationship inferred from Bayesian statistics based on concatenated CAL, TEF1 and TEF3 sequences of 135 strains of Sporothrix species. Bootstrap and posterior probabilities values were added to respective branches (BI/ML/NJ). Branches with bootstrap support values higher than 80 % are indicated in bold.

Fig. 4

Amplified fragment length polymorphism (AFLP) profiles of 122 strains of Sporothrix. Clustering of AFLP banding pattern of isolates of Sporothrix was done by UPGMA. Red vertical bars represents cut-off for distinction of clusters. Strains of S. mexicana and below are phylogenetically unrelated.

Fig. 5

Minimum spanning tree of AFLP data showing the relationships among 135 Sporothrix isolates, showing prevalent endemism of subclusters. Each dot corresponds to a unique genotype.

Fig. 6

Timeline of epidemics and case series caused by three main pathogenic Sporothrix species since 1940. Vertical bars represent gross number of cases, vertical arrows denote case series and sapronoses or zoonoses.

Fig. 7

Schematic overview of the hypothesis for the dissemination of the plant-born pathogen Sporothrix globosa, applied to the large human epidemics occurring in corn crops in north-east China. a. The species has not been found as an endophyte. b. Specific conditions in decaying plant material, such as fermentation, may stimulate excessive growth of the thermodependent yeasts, which facilitates infections in mammals. c. Onset of facial infections during transportation of corn debris. d. Delayed development of human infection during decline of growth in plant debris.

Fig. 8

Diagram of hypothetical processes of evolution from highly diverse ancestral species S. schenckii and clonal offshoots S. globosa and S. brasiliensis. Due to differential selection processes, the derived species differ significantly in virulence, transmission and type of epidemic caused.