title: N-Chlorotaurine Exhibits Fungicidal Activity against Therapy-Refractory Scedosporium Species and Lomentospora prolificans.
abstract: N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against Scedosporium and Lomentospora, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans (formerly Scedosporium prolificans) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1- to 4-log10 reduction in CFU after 4 h and a 4- to >6-log10 reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of Galleria mellonella infected with 1.0 × 10(7) conidia of S. apiospermum and S. boydii died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different Scedosporium and Lomentospora species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Lackner
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Binder
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Reindl
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Gönül
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Hannes
authors.initials: H
authors.lastname: Fankhauser
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Mair
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria m.nagl@i-med.ac.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Nagl
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects; D002700:Chloramines / Q000737:chemistry / Q000494:pharmacology; D025301:Hyphae / Q000187:drug effects / Q000502:physiology; D007814:Larva / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009036:Moths / Q000382:microbiology; D021681:Scedosporium / Q000187:drug effects* / Q000502:physiology; D013172:Spores, Fungal / Q000187:drug effects / Q000502:physiology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000891:Anti-Infective Agents, Local; D000935:Antifungal Agents; D002700:Chloramines; D000643:Ammonium Chloride; D013654:Taurine; C043410:N-chlorotaurine; C030816:chloramine