Josh Engle will present the seminar on Friday, April 10th. The title of his talk is:
Chitin Synthase Gene Expression in Penicillium marneffei in Response to Cell-Wall Stressors
Two links to relevant papers are presented below:
http://crcooper01.people.ysu.edu/yakA-paper-Microbiology160(2014)1929-1939.pdf
Josh Engle did a great job with his presentation Friday. His research is a continuation of the work that was laid out by Dr. Kummasook and Dr. Sumunnakorn on Penicilium marneffei. His focus was on the genetic expression of chitin synthase activity within P. marneffei and how functioning and non-functioning yakA genes affected it. He analyzed the genetic expression of chitin synthase activity of wild type P. marneffei (WT-F4), a yakA mutant strain (ΔyakA), and a ΔyakA compliement strain (CM21) under different cell wall stressors (congo red, sodium dodecyl sulfate, and Calcofluor white). He used qRT-PCR to analyze the expression of chitin synthase after culturing both the mold and fungal colonies of P. maneffei, exposing them to environmental stressors, and isolating and purifying the RNA from the cultures for analysis. When compared to the glucan synthase work being conducted within the same lab that he is working in, it was discovered that his initial results in chitin synthase expression might be a compensatory mechanism for the diminished glucan expression by this mutant strain. Especially since current results show glucan expression is significantly diminished under control condition in this strain.
ReplyDeleteSince Josh’s and Sarah’s seminar presentations are on their research into the expression of the synthases that create the fungal cell-wall of P. marneffei, my question is what other current and interesting research is being conducted on P. marneffei?
Unfortunately it seems not much research is being done on the fungus; although it was first discovered in 1956. Infection by P. marneffei has become more of a problem with a global increase in immunocompromised HIV patients, as Josh mentioned. Infection of the fungus typical presents in patients through swelling of the lymphnodes, spleen and liver; as well as respiratory symptoms such as cough and chest pain.
ReplyDeleteAlthough most clinical reporting seems to be in HIV/AIDS patients, one instance published in the European Respiratory Journal in 2012 showed P. marneffei infection in an immunocompetent man. This perhaps alludes to an increased pathogenicity of the fungus.
I read a paper about how P. marneffei evades the immune system of the host by suppressing macrophage anti-fungal function. Thus, promoting its replication in the host.
ReplyDeleteP. marneffei is believed to achieve this by the phosphorylation and activation of the c-Jun N-terminal kinase 1 and 2 (JNK1/2) pathway. This leads to the production of IL-10 which suppresses the efficacy of the macrophages in getting rid of P. marneffei. Using the specific inhibitor of JNK1/2 (SP600125), it was found that the inhibition of JNK1/2 suppressed P. marneffei-induced tumor necrosis factor-α and IL-10 production; it also help in the reduction of P. marneffei replication. http://www.sciencedirect.com/science/article/pii/S0882401015000492
Since P. marneffei infections (penicilliosis) are typically secondary to immunodeficiency, there has been a lot of research done on the link between the AIDS epidemic and P. marneffei and more importantly on effective ways to treat penicilliosis.
ReplyDeleteAs Ray stated, there is quite a bit of research involving P. marneffei and AIDS/HIV. Here is a paper that talks about using Voriconazole (anti-fungal) in the treatment of P. marneffei primarily in AIDS patients.
Deletehttp://www.ajtmh.org/content/77/2/350.long
Early diagnosis of P. Marneffei infection can improve the outcome of treatment. People are working on developing faster diagnostic tests. Some of these test for antigens in the urine and/or blood.
ReplyDeleteOne experimental test and its trial results are described here:
Kaufman, L., Standard, P. G., Jalbert, M., Kantipong, P., Limpakarnjanarat, K., & Mastro, T. D. (1996). Diagnostic antigenemia tests for penicilliosis marneffei. Journal of clinical microbiology, 34(10), 2503-2505.
Josh did a wonderful job with his seminar on Friday! I hate having to be the one to follow it
ReplyDeleteSome of the most recent research on P. marneffei includes a gene study that was published back in August. Based out of Chiang Mai, Suwunnakorn et al. characterized a mutant with a defective rttA gene. This mutant possessed fewer conidia than the wild type and had slower rates of conidial germination. Based on their research, they were able to determine this gene plays important roles in morphogenesis. Carbohydrate metabolism, stress response, and pathogenesis in P. marneffei.
Josh you did a great job presenting your research!
ReplyDeleteThere is research being conducted on the use of different medications to treat penicilliosis caused by P. marneffei. There is a comparative trial testing the efficacy and safety of itraconazole versus amphotericin B for the acute-phase treatment of penicilliosis.
http://www.seaicrn.org/download/PartnershipProtocol2.pdf
I was really impressed with Josh's presentation skills as well as the PCR data that he presented. Very well done!
ReplyDeleteA couple articles I looked at studied up/down regulation of genes during the dimorphic change between mold to yeast and vice versa. I remember learning there is more cases reported during the wet season than during the dry season. I think someone should do a study on the water supplies in the affected areas because the bamboo rats could play a part in contaminating the water or picking up the fungus from the water.
I really like the point Dylan brings up. Since P. marneffei is thermally dimorphic, I imagine regional climate plays a major role in proliferation. Maybe, understanding how the environment traditionally affects the P. marneffei life cycle will shed light on P. marneffei- human interactions.
DeleteGreat job Josh!
Although P. marneffei is a relatively understudied dimorphic fungi, there other organisms that exist in the world. For example, histoplasma capsulatum, which causative agent for histoplasmosis. However, unlike P. marneffei this fungi can immunocompotent individuals. Research is currently underway at Ohio State in which they were able to determine that H. capsulatam has two mechanisms allowing for it pathogenecity. One being masking of immunostimulatory cell wall molecules and production of extracellular defenses and the other being Beta-glucan-containing fungal cell walls are potent activators of signaling receptors on the surface of macrophages.
ReplyDeleteIt seems quite a lot of research is examining the thermal dimorphic traits of P. marneffei. For instance, one study investigated gene expression levels during phase transition between the mold and yeast forms using next-generation sequencing. There were large clusters of genes which receive simultaneous activation suggesting that neighboring genes act in a concerted effort to bring about physical changes. The transcription factor expressed from the madsA gene seemed to be particularly important since its overexpression promoted mold growth and resisted yeast growth.
ReplyDeletehttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004662
While the general consensus is that P. marneffei is a zoonotic contagion carried by bamboo rats there are several studies being conducted on the possibility of the contagion being harbored within the soil. While it has been isolated from a limited number of soil samples, the transfer from soil to a human has yet to be proven.
ReplyDelete