Title: Azole resistance in Aspergillus fumigatus - clinical isolate screening, culture selection, and genetics
Abstract:
In the United States, invasive aspergillosis (IA), an invasive fungal infection of the upper respiratory tract of immune compromised patients, is usually caused by Aspergilus fumigatus, while Aspergillus flavus represents only a small fraction of IA cases. In some countries A. flavus is the most frequent IA pathogen. Recently, we described a novel, highly virulent, aggressively invasive, and drug resistant IA pathogen, Aspergillus tanneri. In mouse models of IA and in a non-vertebrate insect model we observed distinct virulence profiles for the three Aspergillus species. Comparative genomics showed that A. tanneri had a larger genome than the other Aspergilli, encoding nearly 1900 more genes than A. fumigatus. A. tanneri genes had numerous orthologs in the other two genomes, however an abundance of genes are unique to A. tanneri. Among the unique genes were multiple gene clusters that encode biosynthetic genes for the synthesis of secondary metabolites, suggesting that A. tanneri produces novel secondary metabolites that may play a role in its high level of pathogenicity. Analysis of genes commonly associated with drug resistance showed that A. tanneri carried CYP51A mutations resulting in or contributing to azole resistance. An important issue featured in the A. tanneri fatal cases and in clinical management of IA is the general limitation in treatment options - only four classes of drugs are available in the context of ever-increasing drug resistance. Drugs used to treat fungal infections target only two differences between human and fungal cells: the presence of ergosterol in fungal cell membranes and of glucans in their cell walls. There remains an urgent need to understand the broad range of genes encoded in the genomes of fungal pathogens that participate in the resistance to the clinically therapeutic antifungals employed in treating infections. To identify novel mechanisms that mediate azole resistance in A. fumigatus, we used whole genome sequencing of in vitro selected azole-resistant strains. To further refine the most significant mechanisms required for resistance, we developed a genetic-sexual system that enables the analysis of complex traits in A. fumigatus and revealed that at least 6 mechanisms for azole resistance exist in this organism. These include mutations in the target protein, CYP51A, and in an additional co-target HMG CoA reductase. The results from this study identify novel drug targets in A. fumigatus and also show that next-generation sequencing coupled with classical genetics experiments is a powerful way to identify genes involved in complex traits.
Biography:
Dr. William Nierman is the Director of the Infectious Disease Program at the J. Craig Venter Institute (JCVI). He is also a Professor the George Washington University School of Medicine and has taught Human Genetics at The Johns Hopkins University. He received his BS degree from the US Naval Academy and his PhD degree from the University of California, Berkeley. Dr. Nierman has broad experience in microbial pathogen genomics. His research focus is the genomic and functional analysis of two the levels of pathogen interaction with the human host, that caused by severe acute disease-causing bacterial pathogens, and that caused by fungi that can cause disease only in an immune-system-compromised host. Burkholderia mallei and Burkholderia pseudomallei are severe bacterial pathogens that cause difficult to diagnose but very life threatening diseases, glanders and melioidosis. At the other end of the pathogenicity scale are Aspergillus and Penicillium fungal pathogens which cause invasive or systemic disease in immune compromised or immune suppressed human hosts. Management of the disease in both classes of infections is becoming increasingly compromised by the rapid evolution of drug resistance in the pathogens. Both groups of organisms pose serious public health issues in both developed and in developing countries.
Title: Mycotoxins and their effects in living systems
Abstract:
Some of the most potent toxins are synthesized by fungi. Fungal toxins are the chemicals produced by fungi under certain conditions. They may be classified under different chemical classes. They are not essential for fungal growth or reproduction, but are toxic to plants, animals or humans.
Fungal toxin contamination in certain agricultural commodities has been a significant concern for animal and human health. The major toxin-producing fungi are the species of aspergillus, penicillium, fusarium and alternaria.
Aflatoxins, Citrinin, Fumonisins, Fusaric acid, Moniliformin, AAL-toxins, Alternariol, Ergot alkaloids, Ochratoxin A, and Zearalenone are some of the important fungal toxins responsible for causing economic losses to agriculture, spoilage of food that are often fatal to living systems. This research focuses on toxigenic fungi, toxins and their characteristics with biological effects.
Biography:
Bassmalla has completed her bachelor degree at the age of 22 years from Tanta university. She graduated with GPA=3.45 and participated in many students activities during university time. Also she had several courses related to microbiology and medical analysis.
Title: Evaluation of 1, 3-Beta-D-Glucan assay for diagnosis of invasive fungal infection in pediatric cancer patients
Abstract:
Background & Objective: Serum 1,3-β-D-glucan (BDG) is indicated as a tool for early diagnosis of invasive fungal Infections (IFIs). Although this assay has been evaluated well in adult patients, its role in diagnosis of IFI in paediatric cancer patients is said to be limited. One of the reasons for this could be the cut off value chosen for interpretation of the assay. Different studies have suggested different cut off values to diagnose IFI in adult patients by this assay. Most of the time only single serum samples are available from paediatric cancer patients, also serial testing is not possible due to high cost of the assay. This study was therefore planned with the objective to determine the assays best cut off value for the diagnosis of IFI by single serum samples in paediatric cancer patients.
Biography:
Abrar Ahmad Ph.D Microbiology with 8 years of academic research and 1 year of Industry experience.has research interests in Invasive Fungal Infection.
Title: Chronic pulmonary aspergillosis- Diagnostic challenge
Abstract:
Chronic Pulmonary Aspergillosis (CPA) is pulmonary disease estimated to affect 3 million people world-wide making it an under-recognized, but significant health problem world-wide, which however confers significant morbidity and mortality. The disease is caused by aspergillus species, which can reach respiratory tract by air-borne transmission. Any form of lung injury or illness is predisposing factor for development of CPA, among which most common cause is pulmonary tuberculosis. Such pulmonary injury affects local host defenses enabling aspergillus conidia to germinate within lung. It is crucial to diagnose CPA timely and appropriately to ensure relevant treatment considering similarity of CPA to many other diseases.
Diagnosis of CPA is based on well-established diagnostic criteria , which requires thoracic imaging , direct microbiological evidence of aspergillus infection or an immune response to aspergillus spp . New laboratory diagnostics have been developed specifically for diagnosing CPA, which need to be evaluated specifically for CPA and utilized for diagnosis.
Biography:
Ritu Singhal (MD) is working as Senior Specialist and Quality Co-ordinator in Department of Microbiology, Centre of Excellence (WHO) & National Reference Laboratory (NABL accredited ) for Tuberculosis at National Institute of Tuberculosis and Respiratory Disease, New Delhi. She is national level trainer in molecular technologies in TB for SAARC and Union. She has conceptualized many projects with over 32 publications in peer reviewed National and International Journals. She has been awarded Prof. AN Chakrabarty memorial prize for best published paper in IAMM, year 2017, is recipient of outstanding achievement as Fogarty Fellow in 2014.
Title: Emergence of systemic mycoses emergomycosis worldwide: Current scenario
Abstract:
Emergomycosis is a systemic fungal disease caused by thermally dimorphic fungi belonging to the genus Emergomyces, so named because of their recent emergence worldwide.
Es. pasteurianus, the type species, has been reported from Asia (China and India), Europe (Italy, France, Spain and the Netherlands), and Africa (Uganda and South Africa). Es. africanus has been reported from South Africa and Lesotho. Es. canadensis has been reported from Canada (Saskatchewan) and the United States (Colorado and New Mexico), Es. orientalis from China (Shanxi), and Es. europaeus from Germany. The cases are diagnosed by microscopy, histopathology of sample and isolation of fungus from skin lesion, bone marrow and sputum etc. The identification of the isolates is confirmed by sequencing internal transcribed spacer region of rDNA, beta-tubulin, actin and intein PRP8. The patients are treated with induction with amphotericin B deoxycholate followed by maintenance therapy with itraconazole. Few patients have also responded to therapy with posaconazole.
Internal transcribed spacer (ITS) sequencing of ribosomal DNA is the gold standard for identification but its application is jeopardised in resource limited settings. Furthermore, an affordable, accessible, and feasible diagnostic test is warranted to enable the diagnosis in endemic regions and also for epidemiological surveillance. More scientific inputs are required to understand the geographic range, ecology, epidemiology and immunopathogenesis, clinical features, diagnostic, therapeutic aspects of this mycoses. It is important for clinicians, histopathologists and microbiologists to be aware of such differences in order to avoid a misdiagnosis, as these fungi may be encountered with increasing frequency.
Biography:
Malini R Capoor is a Medical Mycologist and is currently a professor in Microbiology, Vardhman Mahaveer Medical College and Safdarjung Hospital, New Delhi, India, with 19 years experience. She teaches Medical Microbiology, Medical Mycology to undergraduate and post graduate students. She has guided and co-guided post graduate students. Her interests are in the field of systemic fungal infections and dimorphic fungi. She has more than 93 publications (53 international) in the field of medical mycology mainly. She is Principal investigator and coinvestigator of projects from related to medical mycology. She has delivered more than fifty invited lectures in the field of medical mycology in National and international conferences.
She is on editorial board of the Journal of Global Infectious Diseases.
Title: Managing fungal and bacterial risks
Abstract:
In the last two years there have been several high-profile illnesses in cannabis users, notably the e-cigarette, or vaping, product-use associated lung injury (EVALI), and heavy metal poisoning in California and Michigan. While these are undeniably deserving of attention, they have led to a focus on chemical contaminants and causes of illness, rather than microbial ones. With an estimated combined market of over $10B in retail sales this year, it’s not a matter of if, but when will the cannabis industry have its first major microbial or food-borne outbreak and product recall. This can be mitigated by implementing proper quality control measures, but what does that mean? Presented within is a general overview of quality control in 2 aspects of the cannabis industry particularly focusing on bacterial and fungal contamination and steps to mitigate it.
Biography:
Josh Smith has spent the last decade researching alternative anti-microbial therapies in the pharmaceutical industry. In particular, he has spent most of his career developing molecular diagnostic methods and genetically modifying E. coli to prevent or kill off infections. Most recently, he worked on developing treatments for catheterized patients to guard against UTIs as well as clearing wound and skin graft sites prior to treatment. This work led to developing a patent pending new diagnostic test for identifying bacterial infections within 4 hours of receipt by the lab. His graduate degree is in clinical microbiology but, during the course of his education, he spent a large amount of time in microbial genetics, biochemistry, x-ray crystallography, and protein kinetics, particularly with the hemolysin hpmA of P. mirabilis. In 2018, Josh was approached to found Premium CBD Labs, a hemp testing laboratory located in Madison, WI. His focus is bringing the standards and ethical accountability of clinical labs to the cannabis testing industry.