Widespread occurence and evolution of human pathogenic Fusarium
Open Access
- Author:
- Short, Dylan Phillip
- Graduate Program:
- Plant Pathology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- July 27, 2011
- Committee Members:
- David Michael Geiser, Dissertation Advisor/Co-Advisor
David Michael Geiser, Committee Chair/Co-Chair
Maria Del Mar Jiminez Gasco, Committee Member
Gary William Moorman, Committee Member
Seogchan Kang, Committee Member
Eddie Holmes, Committee Member - Keywords:
- mycotic keratitis
opportunistic pathogens
fungi
multilocus sequence typing
phylogenetic diversity
Fusarium
population genetics
species diversity - Abstract:
- We tested the hypothesis that plumbing systems might serve as a significant environmental reservoir of human pathogenic isolates of Fusarium performing the first extensive multilocus sequence typing (MLST) survey of plumbing drain-associated Fusarium isolates, and comparing the diversity observed to the known diversity of clinical Fusarium isolates. We found that 66% of 471 sinks and 80% of 131 buildings surveyed yielded at least one Fusarium culture. The 297 isolates of Fusarium collected were subjected to MLST to identify the phylogenetic species and sequence types (STs) of these isolates. The six most common STs in sinks were identical to those most frequently associated with human infections. We speculate that the most prevalent STs, by virtue of their ability to form and grow in biofilms, are well adapted to plumbing systems. The most common group observed, the Fusarium solani species complex, (FSSC) is the most common group of fusaria associated with life-threatening opportunistic human infections as well as infections of the cornea. Here we present the description and taxonomy of Fusarium fistularum sp. nov., the single most common human pathogen in the genus Fusarium, that was previously known as FSSC Group 2. F. fistularum is genetically diverse, cosmopolitan and associated with biofilms on plumbing surfaces in the environment. Morphologically, F. fistularum isolates show high levels of variation in a range of characteristics that are typical for most concepts of ‘F. solani,’ with many isolates failing to produce sporodochia in culture and possessing aberrant morphological characters. Similar ranges of morphology were observed in three other commonly encountered phylogenetic species in FSSC. Secondary metabolites produced by F. fistularum include anhydrofusarubin, fusarubin, solaniol, and javanicin. A haematonectria-like heterothallic sexual stage was produced for F. fistularum; an epitype was provided for the sexual stage, and described as an addendum to the description of F. fistularum. Most pairings of isolates indicated possible high levels of infertility. In addition, based on a DNA sequence connection with an ex-Type culture, we apply the name F. petroliphilum, elevated to species status from F. solani var. petroliphilum, to another common Fusarium species associated with human infections and biofilms, FSSC 1. To better understand the population dynamics of this F. fistularum for purposes of epidemiology and control, we expanded an existing 3-locus MLST system by adding six novel sequence-based markers developed based on the complete genome sequence of Nectria haematococca Mating Population VI (FSSC 11). 9-locus MLSTs were generated for 231 isolates from six continents and from a variety of sources, including plumbing and from human and animal infections. High levels of genetic diversity and evidence for both recombination and clonality were detected among 111 unique 9-locus STs. Inclusion of the mating type as a tenth marker revealed ten additional STs, indicating that true clones are not well resolved even with ten loci. The most common ST (2-d2), with 49 members, was found in plumbing, contact lenses and lens cases, as well as fusarial keratitis. No evidence for population differentiation between clinical isolates and isolates from environmental sources was found. Cryptic speciation with F. fistularum suggested in the previous three-locus MLST system was not supported with the addition of new loci, but evidence of introgression of ribosomal RNA genes from another strongly supported phylogenetic species also known from plumbing and human infections (FSSC 9), was detected in two isolates of F. fistularum.