The serine peptidase inhibitor TPCK induces several morphophysiological changes in the opportunistic fungal pathogen Candida parapsilosis sensu stricto

2019 ◽  
Vol 57 (8) ◽  
pp. 1024-1037 ◽  
Author(s):  
Rafael M Gandra ◽  
Laura N Silva ◽  
Xênia M Souto ◽  
Leandro S Sangenito ◽  
Lucas P S Cruz ◽  
...  
Keyword(s):  
Cell Biology ◽  
Candida Parapsilosis ◽  
Galleria Mellonella ◽  
Neutral Lipids ◽  
Sensu Stricto ◽  
New Drugs ◽  
Candida Spp ◽  
Cytoplasmic Inclusions ◽  
Chloromethyl Ketone ◽  
Serine Peptidase

AbstractCandida parapsilosis sensu stricto (C. parapsilosis) has emerged as the second/third commonest Candida species isolated from hospitals worldwide. Candida spp. possess numerous virulence attributes, including peptidases that play multiple roles in both physiological and pathological events. So, fungal peptidases are valid targets for new drugs development. With this premise in mind, we have evaluated the effect of serine peptidase inhibitors (SPIs) on both cell biology and virulence aspects of C. parapsilosis. First, five different SPIs, phenylmethylsulfonyl fluoride, benzamidine, 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, N-α-tosyl-L-lysine chloromethyl ketone hydrochloride, and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) were tested, and TPCK showed the best efficacy to arrest fungal growth. Subsequently, the ability of TPCK to modulate physiopathological processes was investigated. Overall, TPCK was able to (i) inhibit the cell-associated serine peptidase activities, (ii) promote morphometric and ultrastructural alterations, (iii) induce an increase in the intracellular oxidation level, which culminates in a vigorous lipid peroxidation and accumulation of neutral lipids in cytoplasmic inclusions, (iv) modulate the expression/exposition of surface structures, such as mannose/glucose-rich glycoconjugates, N-acetylglucosamine-containing molecules, chitin, polypeptides and surface aspartic peptidases, (v) reduce the adhesion to either polystyrene or glass surfaces as well as to partially disarticulate the mature biofilm, (vi) block the fungal interaction with macrophages, and (vii) protect Galleria mellonella from fungal infection, enhancing larvae survivability. Altogether, these results demonstrated that TPCK induced several changes over fungal biology besides the interference with aspects associated to C. parapsilosis virulence and pathogenesis, which indicates that SPIs could be novel promising therapeutic agents in dealing with candidiasis.

Surface, adhesiveness and virulence aspects of Candida haemulonii species complex

2020 ◽  
Vol 58 (7) ◽  
pp. 973-986 ◽  
Author(s):  
Lívia S Ramos ◽  
Simone S C Oliveira ◽  
Laura N Silva ◽  
Marcela Q Granato ◽  
Diego S Gonçalves ◽  
...  
Keyword(s):  
Species Complex ◽  
Galleria Mellonella ◽  
Fungal Infections ◽  
Neutral Lipids ◽  
Clinical Manifestations ◽  
Cell Surface Hydrophobicity ◽  
Candida Spp ◽  
Murine Macrophages ◽  
Candida Haemulonii

Abstract The emerging opportunistic pathogens comprising the Candida haemulonii complex (C. haemulonii [Ch], C. duobushaemulonii [Cd] and C. haemulonii var. vulnera[Chv]) are notable for their intrinsic antifungal resistance. Different clinical manifestations are associated with these fungal infections; however, little is known about their biology and potential virulence attributes. Herein, we evaluated some surface properties of 12 clinical isolates of Ch (n = 5), Cd (n = 4) and Chv (n = 3) as well as their virulence on murine macrophages and Galleria mellonella larvae. Scanning electron microscopy demonstrated the presence of homogeneous populations among the species of the C. haemulonii complex, represented by oval yeasts with surface irregularities able to form aggregates. Cell surface hydrophobicity was isolate-specific, exhibiting high (16.7%), moderate (25.0%) and low (58.3%) hydrophobicity. The isolates had negative surface charge, except for one. Mannose/glucose- and N-acetylglucosamine-containing glycoconjugates were evidenced in considerable amounts in all isolates; however, the surface expression of sialic acid was poorly detected. Cd isolates presented significantly higher amounts of chitin than Ch and Chv. Membrane sterol and lipid bodies, containing neutral lipids, were quite similar among all fungi studied. All isolates adhered to inert surfaces in the order: polystyrene > poly-L-lysine-coated glass > glass. Likewise, they interacted with murine macrophages in a quite similar way. Regarding in vivo virulence, the C. haemulonii species complex were able to kill at least 80% of the larvae after 120 hours. Our results evidenced the ability of C. haemulonii complex to produce potential surface-related virulence attributes, key components that actively participate in the infection process described in Candida spp.

scholarly journals A case series of medically managed Candida parapsilosis complex prosthetic valve endocarditis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Penghao Guo ◽  
Yuting He ◽  
Rui Fan ◽  
Zhongwen Wu ◽  
Yili Chen ◽  
...  
Keyword(s):  
Prosthetic Valve ◽  
Candida Parapsilosis ◽  
Case Series ◽  
Prosthetic Valve Endocarditis ◽  
Sensu Stricto ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Candida Metapsilosis ◽  
Candida Orthopsilosis ◽  
Tof Ms

Abstract Background In recent years, Candida parapsilosis is recognized as a species complex and is composed of Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. Candida parapsilosis complex prosthetic valve endocarditis (PVE) is rare and the survival rate is still low despite of optimal therapeutic strategies. In our report, it is novel to report cases as Candida parapsilosis complex PVE at species and identify Candida parapsilosis using MALDI-TOF MS. Case presentation A series of 4 cases of Candida parapsilosis complex PVE from our institution was reported. Three were infected by Candida parapsilosis sensu stricto and one was infected by Candida metapsilosis. The condition of two cases got better and the other died. Conclusions More attention should be paid to Candida parapsilosis complex PVE and early diagnosis and prompt antibiotic therapy may play a role in the treatment for Candida parapsilosis complex PVE. It is recommended to identify Candida parapsilosis complex at species level and MALDI-TOF MS as an easy, fast and efficient identification method is worth promoting in clinical microbiology

scholarly journals Virulence of Clinical Candida Isolates

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 466
Author(s):  
Martyna Mroczyńska ◽  
Anna Brillowska-Dąbrowska
Keyword(s):  
Virulence Factors ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Hydrolytic Enzymes ◽  
Morphological Transition ◽  
Candida Spp

The factors enabling Candida spp. infections are secretion of hydrolytic enzymes, adherence to surfaces, biofilm formation or morphological transition, and fitness attributes. The aim of this study was to investigate the correlation between known extracellular virulence factors and survival of Galleria mellonella larvae infected with clinical Candida. The 25 isolates were tested and the activity of proteinases among 24/24, phospholipases among 7/22, esterases among 14/23, hemolysins among 18/24, and biofilm formation ability among 18/25 isolates was confirmed. Pathogenicity investigation using G. mellonella larvae as host model demonstrated that C. albicans isolates and C. glabrata isolate were the most virulent and C. krusei isolates were avirulent. C. parapsilosis virulence was identified as varied, C. inconspicua were moderately virulent, and one C. palmioleophila isolate was of low virulence and the remaining isolates of this species were moderately virulent. According to our study, virulence of Candida isolates is related to the expression of proteases, hemolysins, and esterases.

scholarly journals Diagnosis and management of a fatal case of sepsis caused by Candida parapsilosis sensu stricto in a neonate with omphalocele

2018 ◽  
Vol 20 ◽  
pp. 10-14
Author(s):  
Simone Santana ◽  
Tania Salci ◽  
Patricia Andriato ◽  
Patricia Bonfim-Mendonça ◽  
Silvana Caparroz-Assef ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Fatal Case ◽  
Sensu Stricto ◽  
Diagnosis And Management

scholarly journals Candida guilliermondii Complex Is Characterized by High Antifungal Resistance but Low Mortality in 22 Cases of Candidemia

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Laura Judith Marcos-Zambrano ◽  
Mireia Puig-Asensio ◽  
Felipe Pérez-García ◽  
Pilar Escribano ◽  
Carlos Sánchez-Carrillo ◽  
...  
Keyword(s):  
Metabolic Activity ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Sensu Stricto ◽  
Candida Guilliermondii ◽  
Molecular Techniques ◽  
Content Type ◽  
Content Model ◽  
Crystal Violet Assay

ABSTRACT The objectives of our study were to describe the characteristics of patients with Candida guilliermondii candidemia and to perform an in-depth microbiological characterization of isolates and compare them with those of patients with C. albicans candidemia. We described the risk factors and outcomes of 22 patients with candidemia caused by the C. guilliermondii complex. Incident isolates were identified using molecular techniques, and susceptibility to fluconazole, anidulafungin, and micafungin was studied. Biofilm formation was measured using the crystal violet assay (biomass production) and the XTT reduction assay (metabolic activity), and virulence was studied using the Galleria mellonella model. Biofilm formation was compared with that observed for C. albicans. The main conditions predisposing to infection were malignancy (68%), immunosuppressive therapy (59%), and neutropenia (18%). Clinical presentation of candidemia was less severe in patients infected by the C. guilliermondii complex than in patients infected by C. albicans, and 30-day mortality was lower in C. guilliermondii patients (13.6% versus 33.9%, respectively; P = 0.049). Isolates were identified as C. guilliermondii sensu stricto (n = 17) and Candida fermentati (n = 5). The isolates produced biofilms with low metabolic activity and moderate biomass. The G. mellonella model showed that C. guilliermondii was less virulent than C. albicans (mean of 6 days versus 1 day of survival, respectively; P < 0.001). Patients with candidemia caused by the C. guilliermondii complex had severe and debilitating underlying conditions. Overall, the isolates showed diminished susceptibility to fluconazole and echinocandins, although poor biofilm formation and the low virulence were associated with a favorable outcome.

scholarly journals INCIDENCES OF CANDIDA ALBICANS AND NON-ALBICANS AMONG CATHETER-ASSOCIATED URINARY TRACT INFECTION PATIENTS OF AKOLA CITY

2017 ◽  
Vol 10 (11) ◽  
pp. 115
Author(s):  
Khandare Ln ◽  
Barate Dl
Keyword(s):  
Urinary Tract Infection ◽  
Candida Albicans ◽  
Urinary Tract ◽  
Tract Infection ◽  
Candida Parapsilosis ◽  
Opportunistic Infections ◽  
Urine Samples ◽  
Age Group ◽  
Candida Spp ◽  
Catheter Urine

Objective: Candida spp. is the third leading cause of catheter-related infections. Candida species is a part of human microflora and it becomes pathogenic when certain conditions are present and cause an opportunistic infections. The present study was undertaken to determine incidences of Candida albicans and non-albicans among catheterized urinary tract infection (UTI) patients of Akola city.Methods: A total 60 catheter urine samples were collected from patient of all the age group and both sex who had indwelling urinary catheter. The collected catheterized urine samples of patients from various hospitals of Akola city were used for isolation using HiCrome Candida differential agar.Results: It was found that highest frequency of isolation of Candida spp. was from age group 61-70 years. The predominance of male candidate was more than female having Candida spp. in catheter-associated UTI (C-UTI). Among the Candida spp. C. albicans (64.81%) was predominant over non-albicans spp. while in non-albicans Candida krusei and Candida glabrata were predominant showing 11.11% incidences. It was followed by Candida tropicalis (9.2%) and Candida parapsilosis (3.7%).Conclusion: The incidences of C. albicans and non-albicans were high among catheter-associated UTI patients.

scholarly journals Rapid Detection of Echinocandins Resistance by MALDI-TOF MS in Candida parapsilosis Complex

2020 ◽  
Vol 8 (1) ◽  
pp. 109
Author(s):  
Ana Emília M. Roberto ◽  
Danilo E. Xavier ◽  
Esteban E. Vidal ◽  
Cláudia Fernanda de L. Vidal ◽  
Rejane P. Neves ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Incubation Time ◽  
Candida Parapsilosis ◽  
Clinical Laboratory ◽  
Antifungal Susceptibility ◽  
Reference Method ◽  
Sensu Stricto ◽  
Maldi Tof ◽  
Separation Parameter ◽  
Candida Parapsilosis Complex

Mass spectrometry by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) was used to identify and differentiate the pattern of susceptibility of clinical isolates of Candida parapsilosis complex. 17 C. parapsilosis sensu stricto, 2 C. orthopsilosis, and 1 C. metapsilosis strains were obtained from blood cultures, and three different inocula (103, 105, and 107 CFU/mL) were evaluated against three echinocandins at concentrations ranging from 0.03 to 16 µg/mL after incubation of 1 h, 2 h, and 3 h. Drug-free control was used. The spectra obtained at these concentrations were applied to generate composite correlation index (CCI) matrices for each yeast individually. After cross correlations and autocorrelations of each spectra with null (zero) and maximal (16) concentrations, the CCI was used as separation parameter among spectra. Incubation time and inoculum were critical factors to reach higher precision and reliability of this trial. With an incubation time of 3 h and inoculum of 107 CFU/mL, it was possible to determine the breakpoint of the clinical yeasts by MALDI-TOF that presented high agreement with the clinical laboratory standard institute (CLSI) reference method. Herein, we show that mass spectrometry using the MALDI-TOF technique is powerful when it exploits antifungal susceptibility testing assays.

scholarly journals Effect of Probiotics on Oral Candidiasis: A Systematic Review and Meta-Analysis

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2449 ◽  
Author(s):  
Tiziana Mundula ◽  
Federica Ricci ◽  
Beatrice Barbetta ◽  
Michela Baccini ◽  
Amedeo Amedei
Keyword(s):  
Beneficial Effect ◽  
Randomized Clinical Trials ◽  
Population Aging ◽  
Meta Analysis ◽  
Oral Candidiasis ◽  
Oral Intake ◽  
New Drugs ◽  
Candida Spp ◽  
Colony Forming Units ◽  
Effect Of Treatment

Oral candidiasis (OC) is an increasing health problem due to the introduction of new drugs, population aging, and increasing prevalence of chronic illness. This study systematically reviews the effects of the oral intake of probiotics, prebiotics, and synbiotics on Candida spp. counts (colony-forming units (CFU)/mL) in oral and palatal samples. A literature search was conducted. Twelve studies, eight randomized clinical trials (RCTs), and four pre-post studies, resulted as eligible for the meta-analysis, which was performed through a Bayesian random-effects model. All studies analyzed probiotics, and none of them analyzed prebiotics or synbiotics. The treatments effects were measured in terms of odds ratio (OR) of OC (CFU/mL >102, 103, or 104). The meta-analytic OR was 0.71 (95% credibility interval (CrI): 0.37, 1.32), indicating a beneficial effect of treatment; the I2 index was 56.3%. Focusing only on RCTs, the OR was larger and more precise at 0.53 (95% CrI: 0.27, 0.93). The effect of treatment appeared to be larger on denture wearers. Our findings indicate that the intake of probiotics can have a beneficial effect on OC and that the effects could vary according to the patients’ characteristics. Due to the presence of medium–high-risk studies, the results should be interpreted with caution.

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