Stephen Salipante
· MD, PhD – Associate ProfessorVerifiedUniversity of Washington · MD/PhD Program
Active 2003–2026
About
Stephen Salipante is a faculty member in the Department of Laboratory Medicine & Pathology at UW Medicine, University of Washington. The department serves as a regional resource for clinical laboratory services, integrating sophisticated testing and informatics capabilities with the resources of an academic institution to provide clinical and anatomical pathology services. Recognized for excellence in clinical training, research initiatives, and community service, the department serves the five-state WWAMI region, including Washington, Wyoming, Alaska, Montana, and Idaho. While specific details about Dr. Salipante's research focus, background, or key contributions are not provided on the page, his role within this department indicates involvement in clinical laboratory services, research, and education related to laboratory medicine and pathology.
Research topics
- Biology
- Microbiology
- Immunology
- Genetics
- Medicine
- Internal medicine
- Virology
- Computer Science
- Molecular biology
- Chromatography
- Computational biology
- Chemistry
- Mathematics
- Biochemistry
- Telecommunications
- Pathology
Selected publications
2026-02-20
peer-reviewOpen accessBacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the physiological role of the T6SS in Bacteroides within a gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but an eventual fitness cost. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.
Open Forum Infectious Diseases · 2026-02-13
articleOpen accessAbstract We present a case in which vancomycin and dalbavancin exposure preceded emergence of nonsusceptibility to dalbavancin, vancomycin, and daptomycin in a strain of methicillin-resistant Staphylococcus aureus in the setting of a left ventricular assist device (LVAD) infection. We characterized 6 related but genetically unique isolates collected over more than 1 year of recurrent therapy and found that the most resistant isolate acquired multiple walK-related mutations, which has been previously implicated in dalbavancin resistance with vancomycin and daptomycin cross-resistance. Using time-kills at subinhibitory exposures, we found that cefadroxil is synergistic with dalbavancin against the susceptible and resistant strains. This is the first report of dalbavancin nonsusceptibly associated with an LVAD infection, but dalbavancin resistance has been documented previously in association with treatment of endovascular infections. Combination therapy with synergistic and orally bioavailable agents like cefadroxil may be a reasonable strategy to enhance activity and possibly diminish emergence of resistance to dalbavancin.
The Unified Human Virome Database: A toolkit for expanded human virome analysis
bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-02
articleOpen accessCurrent approaches for computationally analyzing viruses within human microbiomes often rely on databases largely composed of fragmented viral genomes from gastrointestinal samples, limiting identification of viruses exclusively found outside the gastrointestinal tract and analyses requiring high-quality genomes. To address these issues, we created the Unified Human Virome Database (UHVDB), comprising 575,497 high-quality, annotated viral genomes from human gastrointestinal, airway, skin, and urogenital sample metagenomes. We developed an associated toolkit that uses UHVDB to characterize viruses and their potential activity from metagenomes, then applied this toolkit to 1,983 airway sample metagenomes from people with cystic fibrosis. Over half of detected viruses lacked evidence of potential activity and were detected transiently. UHVDB is nearly three times larger than prior viral databases and its ability to identify likely active viruses enables rigorous analysis of viruses from diverse human sample types, expanding the capacity to define virus contributions to health and disease.
bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-16
articleOpen accessThe microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures. We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into pellets ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the pellets, and blood was collected to compare corticosterone levels relative to traditional gavage FMT. Plasma corticosterone levels were found to be significantly lower in mice receiving FMT via pellets compared to oral gavage. Furthermore, relative to gavage FMT, microbial signatures of mice receiving FMT via pellets were more similar to those of the donor pellets at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta-diversity distances. Together, these results establish effective antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.
The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome
eLife · 2026-02-20
articleOpen accessBacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the physiological role of the T6SS in Bacteroides within a gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but an eventual fitness cost. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.
Frontiers in Immunology · 2026-04-24
articleOpen accessBackground: The microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures. Methods: We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into aliquots ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the frozen aliquots, and blood was collected to compare corticosterone relative to that after delivery via traditional gavage. Results: Plasma corticosterone levels were found to be significantly lower in mice receiving frozen aliquots compared to oral gavage. Furthermore, relative to controls, microbial signatures of mice receiving FMT via frozen aliquots were more similar to those of the donors at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta diversity distances. Conclusion: Together, these results establish antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.
Discovery and Cryo-EM-Guided Development of a Neuropilin-2-Binding Aptamer for Receptor Antagonism
Journal of the American Chemical Society · 2026-05-21
articleReceptor antagonists represent a major class of targeted cancer therapeutics, yet SELEX-based aptamer discovery often yields high-affinity binders that display limited functional blockade because epitope positioning is not explicitly selected. Herein, we report a multistage discovery and optimization workflow that integrates cell-SELEX, cryo-electron microscopy (cryo-EM), and a structure-constrained follow-up SELEX to generate ligand-blocking antagonists of Neuropilin-2 (NRP2), a cancer-associated coreceptor for vascular endothelial growth factor (VEGF). We performed initial unbiased cell-SELEX against primary human urine-derived renal progenitor cells and identified an NRP2-binding DNA aptamer (NRP2Apt) with nanomolar affinity and high specificity. Using cryo-EM analysis of the NRP2Apt-NRP2 complex, we defined the spatial relationship between aptamer structural elements and the VEGF-binding pocket, providing direct epitope-level insight that is inaccessible from sequence information alone. Guided by these structural observations, we designed an NRP2Apt-scaffolded library in which a VEGF-proximal loop was extended and randomized, and subjected this library to NRP2 protein SELEX, yielding a lead antagonist with substantially enhanced inhibition of VEGF-NRP2 interactions while preserving strong NRP2 affinity. Finally, inspired by the homodimeric form of VEGF ligands, we engineered a bivalent aptamer that displayed enhanced antagonism and markedly increased serum stability. Collectively, we establish a cryo-EM-guided, iterative SELEX framework in which structural constraints are incorporated into library design to optimize the ligand-blocking activity of receptor-binding aptamers.
2026-02-20
peer-reviewOpen accessBacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the physiological role of the T6SS in Bacteroides within a gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but an eventual fitness cost. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.
The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome
eLife · 2026-02-20 · 1 citations
articleOpen accessBacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the physiological role of the T6SS in Bacteroides within a gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but an eventual fitness cost. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.
2026-02-20
peer-reviewOpen accessBacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the physiological role of the T6SS in Bacteroides within a gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but an eventual fitness cost. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.
Recent grants
NIH · $1.3M · 2019
Center for Cystic Fibrosis Translational Research in the Post-CFTR modulator Era
NIH · $29.9M · 2010–2030
NIH · $1.1M · 2018–2022
Frequent coauthors
- 59 shared
Kelsi Penewit
- 56 shared
Adam Waalkes
- 33 shared
Brad T. Cookson
University of Washington
- 33 shared
Colin C. Pritchard
University of Washington
- 29 shared
Brian H. Shirts
Brotman Baty Institute
- 26 shared
Marshall S. Horwitz
University of Washington Medical Center
- 21 shared
William M. Grady
- 21 shared
Elizabeth A. Holmes
University of Washington
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