Joined the Department in 2020
- Food Engineering, Universidad Austral de Chile, Chile, 2002
- Ph.D., Oregon State University, 2009
- Post-Doctoral training, Department of Biomedical Sciences, Oregon State University, 2011
- Previous Faculty Appointments: Universidad Andrés Bello
- Visiting Professor, Faculty of Life Sciences, Universidad Andrés Bello, Chile
Clostridioides difficile spore-host interactions, exosporium assembly and therapeutic development.
Clostridioides difficile is a Gram positive, strictly anaerobic, spore-forming bacterium that causes C. difficile infections (CDI) and is considered as the most frequent hospital-acquired pathogen. With nearly 500,000 cases per year, CDI cause major economic burden to the United States Health Care System. Although standard of care treatments resolve CDI in most cases, a significant proportion of CDI-treated patients (~30%) will experiment a recurrence of the disease with aggravated symptoms. Given that C. difficile is an urgent threat to human health, our group is addressing several independent, and complementary research avenues:
- Mechanisms of C. difficile spore-host interactions. During the infection, C. difficile initiates a sporulation cycle that leads to the formation of new dormant spores in the host, which are key for the recurrence and transmission of the disease. However, the mechanisms that underline C. difficile spore-persistence remain unclear. Our aim is to elucidate how C. difficile spores interact with the intestinal mucosa and persist during the infection. To accomplish this aim, we blend expertise from bacterial genetics, cellular microbiology, cellular biology and advance imaging techniques.
- Exosporium assembly mechanisms of C. difficile spores. The surface of C. difficile spores serves as the primary site of interaction with host surfaces. A major obstacle to develop therapies that remove C. difficile spores from the host and/or environment is the lack of basic understanding of how C. difficile forms the outer exosporium layer of the spore. Our aim is to understand how exosporium assembly occurs during C. difficile spore-formation. To dissect the basis underlying exosporium assembly we use molecular biology, bacterial genetics, biochemical and structural analysis, omics and single cell imaging techniques to understand the mechanisms through which key morphogenetic proteins drive exosporium assembly and interplay with other spore-coat and exosporium constituents.
- Therapeutic development against C. difficile infections. No effective antibiotic and/or vaccine is readily available to resolve CDI and prevent recurrence and transmission of the disease. By understanding how C. difficile interacts with the host and the composition of the spore surface layer, we aim to develop novel therapeutic strategies that prevent C. difficile spore´s interaction with the host´s intestinal mucosa and their persistence during disease. To accomplish these aims we blend knowledge from immune-proteomics and immunology, pharmacology and nanotechnology to design novel alternatives to combat CDI and prevent recurrence and transmission of the disease.
In order to contribute to the control of COVID-19 spread world-wide, we are adapting a protein-display platform, which we have recently used for nasal immunization against C. difficile infections, to express SARS-CoV-2 surface proteins for mucosal immunization studies.
- Chamorro, N, Montero, DA, Gallardo, P, Farfán, M, Contreras, M, De la Fuente, M et al.. Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease. Microb Cell. 2021;8 (9):223-238. doi: 10.15698/mic2021.09.760. PubMed PMID:34527721 PubMed Central PMC8404152.
- Herrera, G, Paredes-Sabja, D, Patarroyo, MA, Ramírez, JD, Muñoz, M. Updating changes in human gut microbial communities associated with Clostridioides difficile infection. Gut Microbes. ;13 (1):1966277. doi: 10.1080/19490976.2021.1966277. PubMed PMID:34486488 PubMed Central PMC8425690.
- Castañeda, S, Patiño, LH, Muñoz, M, Ballesteros, N, Guerrero-Araya, E, Paredes-Sabja, D et al.. Evolution and Epidemic Spread of SARS-CoV-2 in Colombia: A Year into the Pandemic. Vaccines (Basel). 2021;9 (8):. doi: 10.3390/vaccines9080837. PubMed PMID:34451962 PubMed Central PMC8402472.
- Knight, DR, Imwattana, K, Kullin, B, Guerrero-Araya, E, Paredes-Sabja, D, Didelot, X et al.. Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy. Elife. 2021;10 :. doi: 10.7554/eLife.64325. PubMed PMID:34114561 PubMed Central PMC8241443.
- Chiu, PJ, Rathod, J, Hong, YP, Tsai, PJ, Hung, YP, Ko, WC et al.. Clostridioides difficile spores stimulate inflammatory cytokine responses and induce cytotoxicity in macrophages. Anaerobe. 2021;70 :102381. doi: 10.1016/j.anaerobe.2021.102381. PubMed PMID:34082120 .
- Bassères, E, Endres, BT, Montes-Bravo, N, Pérez-Soto, N, Rashid, T, Lancaster, C et al.. Visualization of fidaxomicin association with the exosporium layer of Clostridioides difficile spores. Anaerobe. 2021;69 :102352. doi: 10.1016/j.anaerobe.2021.102352. PubMed PMID:33640461 .
- Castro-Córdova, P, Mora-Uribe, P, Reyes-Ramírez, R, Cofré-Araneda, G, Orozco-Aguilar, J, Brito-Silva, C et al.. Entry of spores into intestinal epithelial cells contributes to recurrence of Clostridioides difficile infection. Nat Commun. 2021;12 (1):1140. doi: 10.1038/s41467-021-21355-5. PubMed PMID:33602902 PubMed Central PMC7893008.
- Romero-Rodríguez, A, Troncoso-Cotal, S, Guerrero-Araya, E, Paredes-Sabja, D. The Clostridioides difficile Cysteine-Rich Exosporium Morphogenetic Protein, CdeC, Exhibits Self-Assembly Properties That Lead to Organized Inclusion Bodies in Escherichia coli. mSphere. 2020;5 (6):. doi: 10.1128/mSphere.01065-20. PubMed PMID:33208520 PubMed Central PMC7677010.
- Muñoz, M, Guerrero-Araya, E, Cortés-Tapia, C, Plaza-Garrido, A, Lawley, TD, Paredes-Sabja, D et al.. Comprehensive genome analyses of Sellimonas intestinalis, a potential biomarker of homeostasis gut recovery. Microb Genom. 2020;6 (12):. doi: 10.1099/mgen.0.000476. PubMed PMID:33206037 PubMed Central PMC8116674.
- Maia, AR, Reyes-Ramírez, R, Pizarro-Guajardo, M, Saggese, A, Ricca, E, Baccigalupi, L et al.. Nasal Immunization with the C-Terminal Domain of Bcla3 Induced Specific IgG Production and Attenuated Disease Symptoms in Mice Infected with Clostridioides difficile Spores. Int J Mol Sci. 2020;21 (18):. doi: 10.3390/ijms21186696. PubMed PMID:32933117 PubMed Central PMC7555657.