<p>Tryptophol Coating Reduces Catheter-Related Cerebral and Pulmonary Infections by <em>Scedosporium apiospermum</em></p>

Abstract

Introduction: Central venous catheter (CVC) is a medical device that is used to administer medication for a long duration. Colonization by an emerging opportunistic pathogen Scedosporium apiospermum in the CVC lumen is frequently reported to cause severe complications in patients. Here, we describe the effect of fungal quorum-sensing molecule (QSM) known as tryptophol (TOH) to control S. apiospermum colonization in catheter tube lumens in both in vitro and in vivo models. Methods: Antifungal susceptibility of TOH against S. apiospermum was compared with voriconazole, and the colony diameter was determined on days 2, 4, and 6. Experimental catheterization rat model was conducted with pre-coating of TOH and voriconazole or an uncoated control and an infection with S. apiospermum. Biofilm formation on the catheter luminal surface was assessed using the scanning electron microscopy, crystal violet, and 2,3-bis(2-methoxy-4-ni-tro-5-sulfophenyl)-5-(phenylamino)-carbonyl-2H-tetra-zolium hydroxide (XTT) reduction assays. Brain and lung samples of catheterized rats were histopathologically assessed. Serum samples from catheterized rats were injected into Galleria mellonella larvae. Survival of catheterized rats and G. mellonella was determined. Results: TOH impeded the growth of S. apiospermum by reducing the colony diameter in a dose-dependent manner. TOH coating remarkably lessened S. apiospermum biofilm formation and fungal cell viability on the catheter luminal surface. Additionally, TOH coating lessens cerebral edema that is associated with abscess and invasive pulmonary damages due to S. apiospermum catheter-related infection. Furthermore, TOH coating also lessened the virulence of S. apiospermum in sera of experimental catheterized rats and extended the survival rate of larvae Galleria mellonella infection model. Conclusion: An alternative modification of catheter by coating with TOH is effective in preventing S. apiospermum colonization in vivo. Our study gives a new strategy to control catheter contamination and prevents nosocomial diseases due to S. apiospermum infection.

Development and efficacy of tryptophol-containing emulgel for reducing subcutaneous fungal nodules from Scedosporium apiospermum eumycetoma

“…In the present study, we found that treatment of TOH lessened the growth of S. apiospermum CBS 117410 in a concentration-dependent manner. In consistent with our previous reports, we found that a moderate concentration (100 μM) of TOH remarkably lessened the growth of S. apiospermum ( 7 ). Although the drug of choice for S. apiospermum infections is VOZ( 39 ), we found that TOH appeared to be as effective as VOZ.…”

“…Antifungal activity of TOH against S. apiospermum CBS 117410 was evaluated using the agar spot assay according to Kitisin et al . ( 7 ). Ten µL of S. apiospermum CBS 117410 conidia (concentration about 1 × 10 5 conidia/mL) were spotted on the surface of SDA plates containing either 10, 100, or 1000 µM of TOH or voriconazole (VOZ; Sigma-Aldrich Inc., St. Louis, MO, USA).…”

“…The pathology of the disease is developed as granulomatous inflammation penetrating the deep dermis and the subcutaneous tissue( 6 ). Moreover, S. apiospermum eumycetoma is endemic among tropical and subtropical regions as well as in Thailand( 4 7 8 ). However, this pathogenic fungus is notorious for its nature of therapy-refractory and is highly resistant to several antifungal agents( 9 ).…”