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.
Clostridium 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 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 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 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.
- 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.
- Pizarro-Guajardo, M, Calderón-Romero, P, Romero-Rodríguez, A, Paredes-Sabja, D. Characterization of Exosporium Layer Variability of Clostridioides difficile Spores in the Epidemically Relevant Strain R20291. Front Microbiol. 2020;11 :1345. doi: 10.3389/fmicb.2020.01345. PubMed PMID:32714296 PubMed Central PMC7343902.
- Álvarez, R, Ortega-Fuentes, C, Queraltó, C, Inostroza, O, Díaz-Yáñez, F, González, R et al.. Evaluation of functionality of type II toxin-antitoxin systems of Clostridioides difficile R20291. Microbiol Res. 2020;239 :126539. doi: 10.1016/j.micres.2020.126539. PubMed PMID:32622285 .
- Guerrero-Araya, E, Meneses, C, Castro-Nallar, E, Guzmán D, AM, Álvarez-Lobos, M, Quesada-Gómez, C et al.. Origin, genomic diversity and microevolution of the Clostridium difficile B1/NAP1/RT027/ST01 strain in Costa Rica, Chile, Honduras and Mexico. Microb Genom. 2020;6 (5):. doi: 10.1099/mgen.0.000355. PubMed PMID:32176604 PubMed Central PMC7371124.
- Maia, AR, Reyes-Ramírez, R, Pizarro-Guajardo, M, Saggese, A, Castro-Córdova, P, Isticato, R et al.. Induction of a Specific Humoral Immune Response by Nasal Delivery of Bcla2ctd of Clostridioides difficile. Int J Mol Sci. 2020;21 (4):. doi: 10.3390/ijms21041277. PubMed PMID:32074955 PubMed Central PMC7072882.
- Castro-Córdova, P, Díaz-Yáñez, F, Muñoz-Miralles, J, Gil, F, Paredes-Sabja, D. Effect of antibiotic to induce Clostridioides difficile-susceptibility and infectious strain in a mouse model of Clostridioides difficile infection and recurrence. Anaerobe. 2020;62 :102149. doi: 10.1016/j.anaerobe.2020.102149. PubMed PMID:31940467 .
- Shen, A, Edwards, AN, Sarker, MR, Paredes-Sabja, D. Sporulation and Germination in Clostridial Pathogens. Microbiol Spectr. 2019;7 (6):. doi: 10.1128/microbiolspec.GPP3-0017-2018. PubMed PMID:31858953 PubMed Central PMC6927485.
- Stojković, V, Ulate, MF, Hidalgo-Villeda, F, Aguilar, E, Monge-Cascante, C, Pizarro-Guajardo, M et al.. cfr(B), cfr(C), and a New cfr-Like Gene, cfr(E), in Clostridium difficile Strains Recovered across Latin America. Antimicrob Agents Chemother. 2019;64 (1):. doi: 10.1128/AAC.01074-19. PubMed PMID:31685464 PubMed Central PMC7187602.
- Pizarro-Guajardo, M, Chamorro-Veloso, N, Vidal, RM, Paredes-Sabja, D. New insights for vaccine development against Clostridium difficile infections. Anaerobe. 2019;58 :73-79. doi: 10.1016/j.anaerobe.2019.04.009. PubMed PMID:31034928 .
- Huang, J, Kelly, CP, Bakirtzi, K, Villafuerte Gálvez, JA, Lyras, D, Mileto, SJ et al.. Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis. Nat Microbiol. 2019;4 (2):269-279. doi: 10.1038/s41564-018-0300-x. PubMed PMID:30510170 PubMed Central PMC6559218.