Mycobacterium abscessus is a non-tuberculous mycobacterial (NTM) species that causes severe pulmonary infections, particularly in immunocompromised patients and those with preexisting lung diseases such as cystic fibrosis. Treating M. abscessus infections is challenging due to its intrinsic antibiotic tolerance and capacity to develop multidrug resistance. To identify novel molecules that can target this pathogen and enhance current treatments, we screened a library of FDA-approved drugs (n = 2,400). Our data shows that Netupitant, a drug commonly used to prevent chemotherapy-induced nausea and vomiting, exhibits potent antibacterial activity against a broad range of M. abscessus clinical isolates, including multidrug-resistant strains, with a minimum inhibitory concentration (MIC) ranging from 4 to 16 µg/mL. Furthermore, in combination with amikacin, a standard treatment for M. abscessus infections, Netupitant demonstrated strong synergistic interactions, as confirmed by checkerboard microdilution and time-kill assays. These findings highlight Netupitant’s potential as a novel therapeutic option for M. abscessus, particularly in combination with existing antibiotics. Future studies exploring its mechanism of action and in vivo efficacy could further advance antibacterial drug discovery for difficult-to-treat NTM infections.

Preterm birth is a leading cause of neonatal morbidity and mortality, with intra-amniotic infection and inflammation being major contributors to early preterm labor (PTL). Despite ongoing research aimed at reducing inflammation in neonates, most studies have focused on post-delivery while few have been done prior to delivery. IL-1 is a central upstream mediator of inflammation in the amniotic cavity and the neonate. IL-1 is a key cytokine that is responsible for induction or propagation of the cytokine cascade responsible for PTL. Rytvela, an interleukin-1 receptor antagonist made up of seven D-amino acids, acts as a selective antagonist of IL-1 signaling, which could be used to act as a therapeutic approach to reduce inflammation and prevent PTL. The purpose of this experiment is to determine if interleukin-1 (IL-1) is a key molecular target for the development of antenatal therapeutics to prevent PTL and fetal injury. We hypothesize that Rytvela administered intravenously to the mother will cross the placenta and be detectable in the amniotic fluid and fetal plasma, suggesting that Rytvela could effectively block IL-1 signaling in the fetus and therefore reduce fetal inflammation. Maternal blood plasma samples were drawn at Day 1, 2, 6 and 10 post infusion. To confirm the transfer of Rytvela to the fetus, we used liquid chromatography-mass spectrometry (LC-MS) to detect the drug, looking at integration, peak identification, and backlog pressures to see if Rytvela is detectable in maternal plasma. Rytvela was detected and luminex plates were run to measure cytokine levels. After GBS infection, Il-1 beta and Il-23 concentrations increased. After Rytvela administration, the concentration of the pro-inflammatory cytokines decreased. Future directions will involve measuring cytokine levels at these time points and correlating them with Rytvela infusion to evaluate the drug’s impact on maternal-fetal inflammation

Pregnant women infected with influenza A virus (IAV) are at higher risk of morbidity, mortality, and poor fetal outcomes. However, the difference in the pathogenesis of IAV between pregnant women and non-pregnant women remains inadequately understood, primarily due to the lack of animal studies that use a translational model of infection. I hypothesized that higher IAV viral load and Type I interferon concentrations would be observed in the lungs and bronchoalveolar lavage of pregnant pig-tail macaques compared to non-pregnant macaques, and that correlating these metrics would yield different results across groups. We inoculated pregnant (n=11) and non-pregnant female (n=18) pig-tail macaques (Macaca nemestrina) with IAV H1N1 (A/California/07/2009) and euthanized them at 5 days post-inoculation, when we expected to observe peak lung pathology. We tested pulmonary function at baseline and study endpoint and conducted clinical assessments daily. I extracted RNA and performed quantitative polymerase chain reactions on the samples to calculate viral load. I also performed enzyme-linked immunosorbent assays to quantify concentrations of Type I interferons (IFN-α, IFN-β). Lastly, I analyzed pulmonary physiology data and clinical assessment scores as a reliable measure of disease severity. A bi-modal distribution of viral load was observed in the lungs of pregnant animals (high>9e5 copies/mg; low<2e4 copies/mg), which was not observed in non-pregnant animals.  When correlating viral load at 5 days post-inoculation with Type I IFN in the lung of the pregnant animals, I found a significant positive correlation between IFN-β and viral load in both the lungs (ρ=0.8, p=0.03) and BAL (ρ=0.9, p=0.02). These results suggest that despite a strong IFN-β response in the lung, a high viral load persisted in the pregnant animals. Next steps could explore whether the kinetics of the pulmonary innate immune response is delayed in pregnancy, which impairs viral clearance. 

The impact of microbial communities plays a large role in the lives of all organisms. Numerous thriving communities of microorganisms are present in places we often overlook. Our research investigates the identification of microbial communities present in the University of Washington Bothell's land, specifically the soil, leaves, and mushrooms commonly found around campus. We aim to support future microbiology lab students by identifying additional species that can be used as unknowns and address common issues students face when sequencing and identifying their known microbes. Our team collected 3 samples from 3 different environments, and each microbial strain was isolated, sequenced, and analyzed using Polymerase Chain Reaction (PCR) to amplify the 16s rRNA gene. The resulting genetic sequences obtained were then matched with NCBI BLAST to determine species identity. Additionally, microscopy and gram-staining were used to classify the bacterial isolates based on their structural characteristics. All collected data will be provided to future students to contribute to their understanding of microbial growth and increase the success rate of replicating and identifying their microbes. We aim to encourage further exploration of microbial life in commonly encountered environments and emphasize the significance of microbes in shaping the ecosystems around us. Understanding these microbial interactions can contribute to a broader understanding in fields such as microbial ecology, medicine, and public health.