Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

Abstract

24Environmental factors modify the physiology of microorganisms, allowing their survival in 25 extreme conditions. However, the influence of chemical contaminants on fungal virulence has 26 been little studied. Sporotrichosis is an emergent fungal disease caused by Sporothrix schenckii, 27 a soil-inhabiting fungus that has been found in polluted environments. Here, we evaluated the 28 adaptive stress response of S. schenckii induced by toluene, a key soil contaminant. The effect 29 on fungal virulence and host immune response was also assessed. The fungus survived up to 30 0.10% toluene in liquid medium. Greater production of melanosomes and enhanced activity 31 superoxide dismutase, associated to increased tolerance to H2O2 were observed in toluene-32 exposed fungi. Intraperitoneal infection of mice with S. schenckii treated with either 0, 0.01 or 33 0.1% of toluene, resulted in greater fungal burden at day 7 post-infection in spleen and liver in 34 the groups infected with fungus treated with toluene 0.1%. A higher production of Il-1β, TNF-35 α, IL-10 and nitric oxyde by peritoneal macrophages and IFNɣ, IL-4 and IL-17 by splenocytes 36 was also observed in that group. Our findings showed that morphological and functional 37 changes induced by toluene leads to increased S. schenckii virulence and antifungal host 38 immune response in our model. 39 40 41 42 43 44 45 78 Aromatic compounds such as benzene, toluene, ethylbenzene and xylene isomers, 79 collectively known as BTEX, are one of the major contributors to environmental pollution. 80 BTEX are extensively used as solvents in many industrial processes and as base reagents for 81 the production of chemicals products. In addition, BTEX are components of gasoline and 82 aviation fuels. They are often released in the environment during production, transport, use and 83 disposal, causing groundwater, surface water, and soil contamination. Toluene has been found 84 in at least 1,012 of the 1,699 National Priorities List sites identified by the Environmental 85 Protection Agency (EPA) and it is included in the Agency for Toxic Substances and Disease 86 Registry (ATSDR) 2017 substance priority list, which is based on a combination of their 87 frequency, toxicity, and potential for human exposure (Agency for Toxic Substances and 88 Disease Registry. ATSDR's Substance Priority List. 2017).89Prenafreta-Boldu isolated several fungi, including S. schenckii, in biofilters exposed to 90 polluted air or hydrocarbon gas streams. The data from this research showed that volatile 91 hydrocarbon-degrading strains are closely related to a very restricted number of pathogenic 92 fungal species that cause severe mycoses, especially neurological infections, in 93 immunocompetent individuals (Prenafeta-Boldú et al., 2006). 94To date, there have been no studies examining the influence of chemical contaminants 95 on the biology of S. schenckii sensu latu. Given that this fungus inhabits soils and this niche is 96 frequently contaminated with oil and their products, the objective of this...

A Recombinant Enolase-Montanide™ PetGel A Vaccine Promotes a Protective Th1 Immune Response against a Highly Virulent Sporothrix schenckii by Toluene Exposure

“…Here, we evaluated the protective effect of PGA formulated with rSsEno against a highly virulent S. schenckii. The enhanced virulence was acquired after fungal exposure to 0.1% of toluene, which induced adaptive changes previously described, including enhanced melanosome formation and stronger antioxidant mechanism compared with the wild type strain [7].…”

“…Control cultures without toluene were included. Fungal viability was determined at fifth day by counting colony forming units (CFU) on Sabouraud dextrose agar (SDA) plates [7].…”

“…Ecological determinants of the genus Sporothrix remain poorly understood [4,5]. However, experimental evidence suggests that environmental contaminants can modify the fungal virulence by reducing the host immunity [6] or modifying the fungal biology [4,7]. Previous studies showed that fungal exposure to toluene, a common soil contaminant that shares the same environmental niche of S. schenckii , is able to increase the S. schenckii virulence [7].…”

“…However, experimental evidence suggests that environmental contaminants can modify the fungal virulence by reducing the host immunity [6] or modifying the fungal biology [4,7]. Previous studies showed that fungal exposure to toluene, a common soil contaminant that shares the same environmental niche of S. schenckii , is able to increase the S. schenckii virulence [7]. Ongoing studies are evaluating the role of chemical contamination and other environmental factors in sporotrichosis outbreaks.…”

“…In this study, we evaluated the protective capacity of an enolase-based vaccine formulated with PGA as an adjuvant, against S. schenckii with increased virulence by experimental exposure to toluene [7].…”