Vancomycin enhances growth and virulence of Trichosporon spp. planktonic cells and biofilms.

Invasive fungal infections (IFIs) are important worldwide health problem, affecting the growing population of immunocompromised patients. Although the majority of IFIs are caused by Candida spp., other fungal species have been increasingly recognized as relevant opportunistic pathogens. Trichosporon spp. are members of skin and gut human microbiota. Since 1980's, invasive trichosporonosis has been considered a significant cause of fungemia in patients with hematological malignancies. As prolonged antibiotic therapy is an important risk factor for IFIs, the present study investigated if vancomycin enhances growth and virulence of Trichosporon. Vancomycin was tested against T. inkin (n = 6) and T. asahii (n = 6) clinical strains. Planktonic cells were evaluated for their metabolic activity and virulence against Caenorhabditis elegans. Biofilms were evaluated for metabolic activity, biomass production, amphotericin B tolerance, induction of persister cells, and ultrastructure. Vancomycin stimulated planktonic growth of Trichosporon spp., increased tolerance to AMB, and potentiates virulence against C. elegans. Vancomycin stimulated growth (metabolic activity and biomass) of Trichosporon spp. biofilms during all stages of development. The antibiotic increased the number of persister cells inside Trichosporon biofilms. These cells showed higher tolerance to AMB than persister cells from VAN-free biofilms. Microscopic analysis showed that VAN increased production of extracellular matrix and cells in T. inkin and T. asahii biofilms. These results suggest that antibiotic exposure may have a direct impact on the pathophysiology of opportunistic trichosporonosis in patients at risk. LAY ABSTRACT This study showed that the vancomycin stimulated Trichosporon growth, induced morphological and physiological changes on their biofilms, and also enhanced their in vivo virulence. Although speculative, the stimulatory effect of vancomycin on fungal cells should be considered in a clinical scenario.

[1]  A. Colombo,et al.  Species distribution and antifungal susceptibility of 358 Trichosporon clinical isolates collected in 24 medical centres. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[2]  R. Cordeiro,et al.  Cefepime and Amoxicillin Increase Metabolism and Enhance Caspofungin Tolerance of Candida albicans Biofilms , 2019, Front. Microbiol..

[3]  A. Shetty,et al.  Trichosporon-Blood Stream Infection. , 2019, The Journal of the Association of Physicians of India.

[4]  A. Colombo,et al.  Trichosporon inkin meningitis in Northeast Brazil: first case report and review of the literature , 2018, BMC Infectious Diseases.

[5]  R. Aguiar Cordeiro,et al.  β-lactam antibiotics & vancomycin increase the growth & virulence of Candida spp. , 2018, Future microbiology.

[6]  B. Kullberg,et al.  Invasive candidiasis , 2018, Nature Reviews Disease Primers.

[7]  Jason B. Lee,et al.  Invasive trichosporonosis treated with voriconazole , 2018, JAAD case reports.

[8]  M. Rybojad,et al.  Trichosporon inkin causing invasive infection with multiple skin abscesses in a renal transplant patient successfully treated with voriconazole , 2017, JAAD case reports.

[9]  F. Bruneel,et al.  Trichosporon inkin disseminated infection , 2017, Intensive Care Medicine.

[10]  C. Hennequin,et al.  Invasive Trichosporon Infection: a Systematic Review on a Re-emerging Fungal Pathogen , 2016, Front. Microbiol..

[11]  Marcos Fábio Gadelha Rocha,et al.  Trichosporon inkin biofilms produce extracellular proteases and exhibit resistance to antifungals. , 2015, Journal of medical microbiology.

[12]  T. Sugita,et al.  Molecular evidence that the opportunistic fungal pathogen Trichosporon asahii is part of the normal fungal microbiota of the human gut based on rRNA genotyping. , 2015, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[13]  Rongya Yang,et al.  Epidemiology and Outcome of Trichosporon Fungemia: A Review of 185 Reported Cases From 1975 to 2014 , 2015, Open forum infectious diseases.

[14]  M. Castanheira,et al.  Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis. , 2015, Medical mycology.

[15]  V. Negi,et al.  Disseminated trichosporonosis due to Trichosporon asahii in a diabetic patient. , 2015, Indian journal of pathology & microbiology.

[16]  G. Goldman,et al.  The development of animal infection models and antifungal efficacy assays against clinical isolates of Trichosporon asahii, T. asteroides and T. inkin , 2015, Virulence.

[17]  L. Pagano,et al.  Uncommon yeast infections in hematological patients: from diagnosis to treatment , 2011, Expert review of anti-infective therapy.

[18]  A. Colombo,et al.  Current Knowledge of Trichosporon spp. and Trichosporonosis , 2011, Clinical Microbiology Reviews.

[19]  I. Accoceberry,et al.  Fatal invasive trichosporonosis due to Trichosporon loubieri in a patient with T-lymphoblastic lymphoma. , 2011, Medical mycology.

[20]  Z. P. Camargo,et al.  Trichosporon species isolated from the perigenital region, urine and catheters of a Brazilian population , 2010 .

[21]  P. Hsueh,et al.  Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  R. Jayaraman,et al.  Bacterial persistence: some new insights into an old phenomenon , 2008, Journal of Biosciences.

[23]  F. Ausubel,et al.  Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay , 2007, PLoS pathogens.

[24]  M. Iezzi,et al.  Biofilm Formation by the Emerging Fungal Pathogen Trichosporon asahii: Development, Architecture, and Antifungal Resistance , 2006, Antimicrobial Agents and Chemotherapy.

[25]  K. Lewis,et al.  Candida albicans Biofilms Produce Antifungal-Tolerant Persister Cells , 2006, Antimicrobial Agents and Chemotherapy.

[26]  Masami Takeuchi,et al.  Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  F. Marty,et al.  Disseminated Trichosporonosis Caused by Trichosporon loubieri , 2003, Journal of Clinical Microbiology.

[28]  K. Lewis Multidrug tolerance of biofilms and persister cells. , 2008, Current topics in microbiology and immunology.

[29]  Clinical,et al.  Reference method for broth dilution antifungal susceptibility testing of yeasts : Approved standard , 2008 .

[30]  P. Nirwan,et al.  Invasive trichosporonosis due to Trichosporon asahii in a non-immunocompromised host: a rare case report. , 2007, Indian journal of medical microbiology.

[31]  Maria José Figueras,et al.  Atlas of clinical fungi. , 2005 .

[32]  M. Ferraro Performance standards for antimicrobial susceptibility testing , 2001 .