Biology subjects

Simbassa, S. B.

Publications and source records attributed to Simbassa, S. B..

2 recordsLinked to original sources

bioRxiv2024

Schistosome esophageal gland factor MEG-8.2 drives host cell lysis and interacts with host immune proteins

Schistosomes are blood flukes that ingest large amounts of host blood during their intra-mammalian stage. The ingested blood contains leukocytes that can be harmful, yet the parasites survive inside the host for decades, reflecting superb immune evasion mechanisms that remain poorly understood. Our previous work discovered that FoxA, a forkhead transcription factor, drives the production of the esophageal gland, an anterior digestive organ essential for degrading the ingested leukocytes and for in vivo survival. However, a comprehensive molecular makeup of the esophageal gland remains unclear. Importantly, which of the esophageal gland factors are responsible for degrading the ingested leukocytes, their mechanism of action, and how such a function relates to parasite survival and immune evasion remains unknown. Here, we identify additional esophageal gland genes by taking a comparative transcriptomics approach to identify transcripts altered in foxA knockdown adult schistosomes. A targeted RNAi screen coupled with biochemistry reveals that specific domains of the micro-exon gene MEG-8.2, can drive host cell lysis in a concentration-dependent manner. Using pull-down assays coupled with mass spectrometry, we discover that MEG-8.2 interacts with several host membrane and extracellular proteins that play important roles in activating innate and/or adaptive immunity. Together, our findings suggest a dual role for MEG-8.2 in effectively lysing the ingested cells in the esophageal lumen and interacting with specific host proteins to neutralize or suppress the host immunity. These findings lay an important foundation for exploiting esophageal gland factors to treat schistosomiasis.

microbiology↗

bioRxiv2021

Antimicrobial Effects of Ibuprofen Combined with Standard of Care Antimicrobials against Cystic Fibrosis Pathogens

Cystic Fibrosis (CF) is a common fatal genetic disease caused by mutations happened to cystic fibrosis transmembrane conductance regulator (CFTR) gene. Lungs of CF patients are often colonized or infected with microorganisms. Drug resistant bacterial infection has been problematic in cystic fibrosis patient. The chronic bacterial infections and concomitant airway inflammation could damage the lung and lead to respiratory failure. Several clinical trials have demonstrated that high-dose ibuprofen reduces the rate of pulmonary function decline in CF patients. This beneficial effect has been attributed to the anti-inflammatory properties of ibuprofen. Previously, we have confirmed that high-dose ibuprofen demonstrated antimicrobial activity against P. aeruginosa in in vitro and in vivo. However, no study has examined the antimicrobial effect of combining ibuprofen with standard-of-care (SoC) antimicrobials. Here, we evaluated possible synergistic activity of combinations of common nonsteroidal anti-inflammatory drugs (NSAIDs), namely, aspirin, naproxen, and ibuprofen, with commonly used antibiotics for CF patients. The drug combinations were screened against different CF clinical isolates. Drugs that demonstrated efficacy in the presence of ibuprofen were further verified synergistic effects between these antimicrobials and NSAIDs. Finally, the survival analysis of an P. aeruginosa murine infection model was used to demonstrate the efficacy of synergistic combination. Our results suggest that combinations of ibuprofen with commonly used antibiotics demonstrate synergistic antimicrobial activity against drug resistant, clinical bacterial strains in in vitro. The efficacy of combination ceftazidime and ibuprofen was demonstrated in in vivo.

microbiology↗