Welcome to IMC 2018 International Mycological Congress
Conference Calendar
Genetic diversity and phenotypic variability in the emerging fungal pathogen Candida auris
- G. Bravo Ruiz
- Z. Ross
- S. Stoichkova
- N. Gow
- A. Lorenz
Abstract
Abstract
Candida auris has been identified as a medically relevant, drug-resistant fungus only in 2009, and is thus a rare example of a completely new pathogenic microbe emerging in the spotlight of global health care. Its emergence and population structure are unusual in many respects (according to current research four distinct geographical clades can be discerned). Because of the recent emergence of C. auris, its life cycle and general biology is still enigmatic. Inferences from research on the widely-studied C. albicans are not always transferable to C. auris, because of the large evolutionary distance between them. Research in our laboratory and by other groups indicate that C. auris and C. albicans display substantial difference in their cell biology. To provide a better understanding of the phenotypic diversity of C. auris – which, ultimately, will enable the Medical Mycology community to progress research into novel diagnostics and therapies – our laboratory studied the cellular and chromosomal features of a series of C. auris strains representing the four main geographical clades to understand its genome organization and variation on a species-wide level. Genome size measurements and electrophoretic karyotyping revealed C. auris to be a haploid species (in line with whole-genome sequencing by us and other groups). C. auris isolates have a plastic karyotype containing 5-7 chromosomes with substantial chromosome number and size variation, both within and between geographical clades. This plasticity of karyotypes within a clade was somewhat unexpected considering the uniformity of C. auris on a DNA sequence level belonging to the same geographical clade. This indicates that genome rearrangement on a chromosomal level potentially is a mechanism C. auris employs to generate genetic diversity during adaptation to environmental challenges. We are interested in how diversity is generated in C. auris and how it affects fundamental features, including growth and stress response, and clinically relevant traits, such as virulence and drug resistance. Recent experiments on C. auris phenotypic diversity between clinical isolates in terms of cell morphology and stress response will be discussed.Global Emergence of the Pathogenic Yeast Candida auris
- E. Johnson
Abstract
Abstract
Most human systemic yeast infections are endogenous in origin and until recently fungal outbreaks involving yeast species were rare and involved small numbers of patients in single units. The emergence and global spread of the pathogenic yeast Candida auris, first recognised in 2009, has been unprecedented; there have now been nosocomial candidaemia outbreaks in high intensity care settings on five continents reported in a relatively short timescale. There are four recognised clades of Candida auris, each of which is associated with emergence and initial subsequent spread in a defined geographical area; the first reported Japanese clade, a South Asian clade, a South African clade and a South American clade. However, with global travel and migration now commonplace several different clades have been found circulating in other countries such as the UK and the USA suggesting multiple independent introductions. Mortality rates as high as 60% associated with deep-seated Candida auris infection have been reported in some countries, although attributable mortality is often hard to establish in the high intensity care settings in which most outbreaks have been reported. Candida auris often displays drug resistance, most often to fluconazole but many strains are also resistant to other azoles and sometimes several different antifungal classes. In addition to a worrying innate drug resistance profile, drug resistance also appears to develop quite readily on therapy. This yeast has a propensity to spread from patient to patient and to persist in the environment and index cases are often associated with multiple cases of colonisation of patients in adjacent areas, sometimes leading to subsequent infections. Even with rigorous infection control measures outbreaks have been difficult to control. This talk will discuss some of the findings on the biology, pathogenicity, biofilm formation and resistance mechanisms of this emerging pathogen.Using whole genome sequencing to elucidate the origins and timeline of Cryptococcus gattii species complex emergence in North America
- S. Lockhart
Abstract
Abstract
Cryptococcus gattii species complex (SC) is a group of at least four species of Basidiomycete yeasts that are common in the environment in tropical and subtropical regions. A recent increase in surveillance for the SC allowed more frequent recognition of C. gattii SC as the cause of human disease in temperate environments as well. In the last two decades C. gattii SC has emerged as a major pathogen in the temperate Pacific Northwest (PNW) of North America. The origin and timeline of this emergence was elucidated using Illumina whole genome sequencing (WGS) and SNP calling. Using a worldwide collection of C. deuterogattii isolates it was shown that the origin of the emergence of this species in the PNW was most likely the Brazilian Amazon rainforest. Using Bayesian Evolutionary Analysis by Sampling Trees (BEAST) it was shown that the North American introduction and emergence most likely happened within the last 100 years and that there were at least three separate introductions. The PNW emergence of C. deuterogattii served as the baseline for analysis of C. gattii sensu stricto in the Southeastern United States. Although less frequently encountered clinically, BEAST analysis showed that the introduction of C. gattii in the Southeastern US likely took place thousands of years ago as opposed to a hundred years ago for C. deuterogattii in the PNW.
Maldi-Tof MS for the identification of filamentous fungi; implications for the clinical lab
- M. Hendrickx
- P. Becker
- D. Stubbe
- A. Normand
- R. Piarroux
Abstract
Abstract
Though important advances have been made over the past decades at the level of identification of filamentous fungi, it remains quite a challenge. Taking into account that the number of patients at risk for invasive fungal disease (IFD) is increasing and that superficial dermatophyte infections of skin and nails are affecting about 25% of the world’s population, there is a need for reliable, fast and cost-effective identification methods. Species-level identification is critical for correct patient treatment, and it is generally accepted that a rapid diagnosis, coupled to the early onset of the appropriate treatment, leads to a better patient outcome.
Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) has already been widely used in the clinical routine for the identification of bacteria and yeasts. Its implementation for the identification of molds has been delayed, due to several reasons. Because of their tough cell wall, a protein extraction protocol needs to be applied, and the heterogeneity of the cultures implies that cultivation and sample processing have to be standardized as much as possible. Furthermore, extended reference spectra databases have been lacking.
In the frame of the BCCM/IHEM collection of biomedical fungi, and in collaboration with French colleagues, we have developed an in house reference spectra database consisting of 1913 strains, belonging to 938 species and 246 genera. This database is currently, to the best of our knowledge, the largest reference spectra database in the world. This database has been challenged in different clinical settings for its capacity to identify clinical isolates, including closely related species and dermatophytes. Based upon this database, MALDI-TOF MS has moreover been implemented in the routine of the BCCM/IHEM quality control (ISO17025 accreditation).
The same set of strains has been used for the development of an online MALDI reference spectra database. This online tool is freely available, and was validated with clinical isolated from Belgium and France. It is now routinely used by many other laboratories throughout the world.
In conclusion, MALDI-TOF MS is a fast, reliable and cost effective method for the identification of filamentous fungi, which van successfully be implemented in a clinical routine setting.
Global emerging azole resistance in Aspergillus fumigatus: one health and the environment
- J. Meis
Abstract
Abstract
Azole antifungals play an important role in the management of fungal infections. However in the last decade azole resistance in Aspergillus fumigatus has been increasingly reported and this is potentially complicating the effective management of these diseases. Started as a clinical rarity in the last decade of the 20th century, less than 15 years later the potential problem of resistance in Aspergillus infections has been recognized on all continents. The higher mortality rates observed in patients with invasive aspergillosis caused by azole resistant A. fumigatus pose serious challenges to the mycologist for timely identification of resistance and appropriate therapeutic interventions. The ‘TR34/L98H’ mutation in the cyp51A gene of A. fumigatus , which is asscociated with azole fungicide use is still responsible for most multi-azole resistance seen in many European and Asian countries. Azole-resistant isolates carrying this mutation have been reported from both patients and the environment. Further, several newly emerging resistance mutations are recognized with ‘TR46/Y121F/T289A’, conferring high voriconazole and variable itraconazole MICs, being now the second most common. Many more resistance mutations associated with environmental selection such as ‘TR53’ and ‘TR92/Y121F/T289A’ are being describedadding to the emerging problem. Environmental screening and routine antifungal susceptibility testing of clinically significant isolates should be considered in order to develop guidelines for local and national purposes. Considering that azole antifungal drugs are the mainstay of (oral) therapy, especially for chronic invasive and allergic aspergillosis, emergence of resistance will have profound impact on healthcare. This presentation highlights the global development of resistance in A. fumigatus and the associated impending clinical treatment problem.Risk factors of vulvo-vaginal candidiasis and antifungal susceptibility pattern of Candida species isolated from women of reproductive age group
- L. Maghari-Capio
Abstract
Abstract
Vulvo-vaginal candidiasis (VVC) is a widespread inflammatory condition of female genital tract and most encountered problem that affects a large fraction of women in a population. The condition is caused by numerous microorganisms involving yeast. This study was conducted to examine the risk factors of vulvo-vaginal candidiasis and to evaluate the in-vitro sensitivities of the isolated Candida species to six antifungal agents. Vaginal, endocervical and urine samples were taken from consenting women. Patients completed a questionnaire assessing the clinico-demographic and risk factors of candidiasis. Standard microbiological techniques such as Lactophenol Cotton Blue Stain, Germ Tube Technique, chlamydospore formation, wet mount and culture were used to analyse the samples. Frequency, percentile and chi- square tests were performed. From a total of 86 respondents, less than one third (30.23 %, 26) were from the outpatient charity department and 69.77 %, 60 came from the outpatient private physician’s clinic. Respondents between 41 and 45 years old had the highest frequency of Candida infection (9, 28.12%). Majority of the respondents positive for candidiasis were married. Out of 32 respondents, two (6.25%) had sexual contact with someone having candidiasis. C. krusei was isolated from patients who had sexual contact with the same sex. A total of three (9.37%) patients had multiple sex partners. There were 11 (34.37 %) Candida species isolated from patients with history of candidiasis in the family. Vaginal and labial itchiness and abnormal discharges showed the highest distribution for Candida species. Antifungal susceptibility testing revealed that eighty (88.33%) out of the 96 species isolates were susceptible to amphotericin-B, 38 (39.58%) to Griseofulvin, 72 (75.00%) to Sporonox, 21 (21.88%) to Nizoral, 15 (15.63%) to Diflucan and 78 (81.25%) to Nystatin. The results of the study revealed that sexual activities and high level of reported risk behavior contributed to the development of VVC also this finding support literatures that antifungal prescription should be only given once the proper identification of the Candida species has been performed.Furthermore, improperly prescribed antifungal agents may lead to drug resistant.