Aspergillus fumigatus Hyphal Damage Caused by Noninvasive Radiofrequency Field-Induced Hyperthermia

Abstract

We studied the effect of noninvasive radiofrequency-induced hyperthermia on the viability of Aspergillus fumigatus hyphae in vitro. Radiofrequency-induced hyperthermia resulted in significant (>70%, P < 0.0001) hyphal damage in a time and thermal dose-dependent fashion as assessed by XTT [(sodium 2,3,-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl] (1)-2H-tetrazolium inner salt)], DiBAC [bis-(1,3-dibutylbarbituric acid) trimethine oxonol] staining, and transmission electron microscopy. For comparison, water bath hyperthermia was used over the range of 45 to 55°C to study hyphal damage. Radiofrequency-induced hyperthermia resulted in severe damage to the outer fibrillar layer of hyphae at a shorter treatment time compared to water bath hyperthermia. Our preliminary data suggest that radiofrequency-induced hyperthermia might be an additional therapeutic approach to use in the management of mold infections.A spergillosis is the most common opportunistic invasive mold infection and is a frequent cause of death in patients with hematological malignancies and transplant recipients (1). Despite improvements in diagnosis and antifungal drug development, novel strategies to combat Aspergillus infections are still needed. Such strategies should be specific, potent, and unaffected by resistance to conventional antifungals and should have the potential to provide synergistic activity with other antifungal therapies.Hyperthermia is a promising therapeutic approach that is being investigated for the treatment of both superficial and deepseated cancers (2). Specifically, noninvasive radiofrequency hyperthermia (RFHT) has shown promise in the treatment of hepatic and pancreatic carcinomas (3, 4). The radio waves used in RFHT have a frequency of 13.56 MHz, allowing tissue penetration to depths greater than 30 cm. This contrasts with the superficial penetration depths (Ͻ1 cm) of hyperthermia delivery systems that use near-infrared and microwave frequencies (5). Also, RFHT-based therapy for cancer can be enhanced and targeted using antibody-conjugated gold nanoparticles (4, 5).Because invasive aspergillosis and cancer have similar biological patterns of invasion and mass-like growth (6), we sought to determine the effect of RFHT on the viability of Aspergillus fumigatus hyphae. We hypothesized that RFHT could damage A. fumigatus hyphae. We found that RFHT inhibits A. fumigatus hyphal growth and damages hyphal structures in a dose-dependent fashion. These results indicate that noninvasive RFHT should be validated in vivo as an adjunct modality in treatment of invasive aspergillosis. MATERIALS AND METHODSFungal isolate. The reference A. fumigatus strain Af293 was used in the present study. To obtain conidia, Af293 was plated on yeast agar glucose plates containing 0.5% (wt/vol) yeast extract, 1.0% (wt/vol) dextrose, 0.2% (wt/vol) vitamin mixture, 0.1% (wt/vol) trace elements, 1.5% (wt/ vol) agar, and 1.0% (wt/vol) MgSO 4 at 37°C. The conidia were harvested 2 days later, counted using a hemocytometer, and suspended in...

Magnetic hyperthermia adjunctive therapy for fungi: in vitro studies against Candida albicans

“…It is reported that cumulative equivalent minutes (CEM 43 ), the metric of thermal tissue damage at 43 C, CEM 43 ¼ 2.7 min can damage cornea when hyperthermia achieved by ultrasound, whereas diode laser heating did not show any damage in the cornea at CEM 43 up to 1.26 Ã 10 3 min [3]. Kaluorachi et al have demonstrated Aspergillus fumigatus hyphal damage caused by noninvasive radiofrequency field induced hyperthermia (RFHT) [16]. RFHT exposure resulted in damage of 70% of the hyphae over 5 min and a 10 min exposure to RFHT at 48.09 caused extreme hyphal damage (>90%).…”