Addison Duda

All Publications

• An Engineered Prodrug Selectively Suppresses β-Lactam-Resistant Bacteria in a Mixed Microbial Setting. ACS infectious diseases Duda, A. M., Ma, H. R., Villalobos, C. A., Kuhn, S. A., Angle, S. S., He, K., Jackson, A. C., Suh, C. M., Puccio, E. A., Anderson, D. J., Fowler, V. G., You, L., Franz, K. J. 2025

  Abstract

  The rise of β-lactam resistance necessitates new strategies to combat bacterial infections. We purposefully engineered the β-lactam prodrug AcephPT to exploit β-lactamase activity to selectively suppress resistant bacteria producing extended-spectrum-β-lactamases (ESBLs). Selective targeting of resistant bacteria requires avoiding interaction with penicillin-binding proteins, the conventional targets of β-lactam antibiotics, while maintaining recognition by ESBLs to activate AcephPT only in resistant cells. We show that AcephPT selectively suppresses Gram-negative ESBL-producing bacteria in clonal populations and in mixed microbial cultures, with effective selectivity for both lab strains and clinical isolates expressing ESBLs. Time-course NMR experiments confirm the hydrolytic activation of AcephPT exclusively by ESBL-producing bacteria. In mixed microbial cultures, AcephPT suppresses proliferation of an ESBL-producing strain while sustaining growth of β-lactamase-nonproducing bacteria, highlighting its potential to combat β-lactam resistance while promoting antimicrobial stewardship.

  View details for DOI 10.1021/acsinfecdis.5c00179

  View details for PubMedID 40503650

• Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases. Science advances Sokratian, A., Zhou, Y., Tatli, M., Burbidge, K. J., Xu, E., Viverette, E., Donzelli, S., Duda, A. M., Yuan, Y., Li, H., Strader, S., Patel, N., Shiell, L., Malankhanova, T., Chen, O., Mazzulli, J. R., Perera, L., Stahlberg, H., Borgnia, M., Bartesaghi, A., Lashuel, H. A., West, A. B. 2024; 10 (44): eadq3539

  Abstract

  The intricate process of α-synuclein aggregation and fibrillization holds pivotal roles in Parkinson's disease (PD) and multiple system atrophy (MSA). While mouse α-synuclein can fibrillize in vitro, whether these fibrils commonly used in research to induce this process or form can reproduce structures in the human brain remains unknown. Here, we report the first atomic structure of mouse α-synuclein fibrils, which was solved in parallel by two independent teams. The structure shows striking similarity to MSA-amplified and PD-associated E46K fibrils. However, mouse α-synuclein fibrils display altered packing arrangements, reduced hydrophobicity, and heightened fragmentation sensitivity and evoke only weak immunological responses. Furthermore, mouse α-synuclein fibrils exhibit exacerbated pathological spread in neurons and humanized α-synuclein mice. These findings provide critical insights into the structural underpinnings of α-synuclein pathogenicity and emphasize a need to reassess the role of mouse α-synuclein fibrils in the development of related diagnostic probes and therapeutic interventions.

  View details for DOI 10.1126/sciadv.adq3539

  View details for PubMedID 39485845

  View details for PubMedCentralID PMC11800946

• Anionic nanoplastic contaminants promote Parkinson's disease-associated α-synuclein aggregation. Science advances Liu, Z., Sokratian, A., Duda, A. M., Xu, E., Stanhope, C., Fu, A., Strader, S., Li, H., Yuan, Y., Bobay, B. G., Sipe, J., Bai, K., Lundgaard, I., Liu, N., Hernandez, B., Bowes Rickman, C., Miller, S. E., West, A. B. 2023; 9 (46): eadi8716

  Abstract

  Recent studies have identified increasing levels of nanoplastic pollution in the environment. Here, we find that anionic nanoplastic contaminants potently precipitate the formation and propagation of α-synuclein protein fibrils through a high-affinity interaction with the amphipathic and non-amyloid component (NAC) domains in α-synuclein. Nanoplastics can internalize in neurons through clathrin-dependent endocytosis, causing a mild lysosomal impairment that slows the degradation of aggregated α-synuclein. In mice, nanoplastics combine with α-synuclein fibrils to exacerbate the spread of α-synuclein pathology across interconnected vulnerable brain regions, including the strong induction of α-synuclein inclusions in dopaminergic neurons in the substantia nigra. These results highlight a potential link for further exploration between nanoplastic pollution and α-synuclein aggregation associated with Parkinson's disease and related dementias.

  View details for DOI 10.1126/sciadv.adi8716

  View details for PubMedID 37976362

  View details for PubMedCentralID PMC10656074

• Intramolecular Oxidative Diaryl Coupling of Tetrasubstituted Diphenylamines for the Preparation of Bis(trifluoromethyl) Dimethyl Carbazoles SYNOPEN Duda, A. M., Giurini, M. T., Gillmore, J. G., Guarr, T. F. 2021; 05 (04): 308-313

  View details for DOI 10.1055/a-1662-7462

  View details for Web of Science ID 000716699400001