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Article ; Online: The Inovirus Pf4 Triggers Antiviral Responses and Disrupts the Proliferation of Airway Basal Epithelial Cells.

Popescu, Medeea C / Haddock, Naomi L / Burgener, Elizabeth B / Rojas-Hernandez, Laura S / Kaber, Gernot / Hargil, Aviv / Bollyky, Paul L / Milla, Carlos E

Viruses

2024 Volume 16, Issue 1

Abstract: Background: The inovirus Pf4 is a lysogenic bacteriophage of : Methods: Primary BCs isolated from pwCF and wild-type (WT) donors were cultured in vitro and exposed to Pf4 or bacterial Lipopolysaccharide (LPS) followed by transcriptomic and functional ...

Abstract	Background: The inovirus Pf4 is a lysogenic bacteriophage of Methods: Primary BCs isolated from pwCF and wild-type (WT) donors were cultured in vitro and exposed to Pf4 or bacterial Lipopolysaccharide (LPS) followed by transcriptomic and functional assays. Results: We found that BCs internalized Pf4 and this elicits a strong antiviral response as well as neutrophil chemokine production. Further, we found that BCs that take up Pf4 demonstrate defective migration and proliferation. Conclusions: Our findings are highly suggestive of Pf4 playing a role in the pathogenicity of
MeSH term(s)	Animals ; Humans ; Respiratory System ; Epithelial Cells ; Epithelium ; Cystic Fibrosis ; Cell Proliferation ; Antiviral Agents ; Pseudomonas aeruginosa/physiology ; Pseudomonas Infections/microbiology ; Mammals
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2024-01-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010165
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Innate Sense of Bacteriophages.

Bollyky, Paul L / Secor, Patrick R

Cell host & microbe

2019 Volume 25, Issue 2, Page(s) 177–179

Abstract: Perturbation of the gut microbiota is associated with inflammatory bowel disease, obesity, and even cancer. In this issue of Cell Host & Microbe, Gogokhia et al. 2019 sought to kill cancer-causing bacteria with bacteriophages. However, the bacteriophages ...

Abstract	Perturbation of the gut microbiota is associated with inflammatory bowel disease, obesity, and even cancer. In this issue of Cell Host & Microbe, Gogokhia et al. 2019 sought to kill cancer-causing bacteria with bacteriophages. However, the bacteriophages themselves directly stimulated an immune response, which worsened inflammatory bowel disease pathogenesis.
MeSH term(s)	Bacteriophages ; Colitis ; Humans ; Inflammation ; Inflammatory Bowel Diseases/microbiology ; Intestines/microbiology
Language	English
Publishing date	2019-02-19
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2019.01.020
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Zs.A 6578: Show issues

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Article ; Online: Targeted deletion of Pf prophages from diverse

Schmidt, Amelia K / Schwartzkopf, Caleb M / Pourtois, Julie D / Burgener, Elizabeth B / Faith, Dominick R / Joyce, Alex / Lamma, Tyrza / Kumar, Geetha / Bollyky, Paul L / Secor, Patrick R

Journal of bacteriology

2024 , Page(s) e0040223

Abstract: Pseudomonas ... ...

Abstract	Pseudomonas aeruginosa
Language	English
Publishing date	2024-04-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/jb.00402-23
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Article ; Online: Bacterial outer membrane vesicles bound to bacteriophages modulate neutrophil responses to bacterial infection.

Pennetzdorfer, Nina / Popescu, Medeea C / Haddock, Naomi L / Dupuy, Fannie / Kaber, Gernot / Hargil, Aviv / Johansson, Patrik K / Enejder, Annika / Bollyky, Paul L

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1250339

Abstract: Pseudomonas ... ...

Abstract	Pseudomonas aeruginosa
MeSH term(s)	Humans ; Animals ; Mice ; Neutrophils/metabolism ; Bacteriophages ; Bacterial Outer Membrane/metabolism ; Toll-Like Receptor 3 ; Pseudomonas Infections/microbiology ; Endotoxins ; Mammals
Chemical Substances	Toll-Like Receptor 3 ; Endotoxins
Language	English
Publishing date	2023-10-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1250339
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Article: Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding.

Chen, Qingquan / Cai, Pam / Chang, Tony Hong Wei / Burgener, Elizabeth / Kratochvil, Michael J / Gupta, Aditi / Hargil, Aviv / Secor, Patrick R / Nielsen, Josefine Eilsø / Barron, Annelise E / Milla, Carlos / Heilshorn, Sarah C / Spakowitz, Andy / Bollyky, Paul L

bioRxiv : the preprint server for biology

2024

Abstract: Despite great progress in the field, ... ...

Abstract	Despite great progress in the field, chronic
Language	English
Publishing date	2024-03-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.10.584330
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Article ; Online: Bacteriophages and the Immune System.

Popescu, Medeea / Van Belleghem, Jonas D / Khosravi, Arya / Bollyky, Paul L

Annual review of virology

2021 Volume 8, Issue 1, Page(s) 415–435

Abstract: Bacteriophages-viruses that infect bacteria-are abundant within our bodies, but their significance to human health is only beginning to be explored. Here, we synthesize what is currently known about our phageome and its interactions with the immune ... ...

Abstract	Bacteriophages-viruses that infect bacteria-are abundant within our bodies, but their significance to human health is only beginning to be explored. Here, we synthesize what is currently known about our phageome and its interactions with the immune system. We first review how phages indirectly affect immunity via bacterial expression of phage-encoded proteins. We next review how phages directly influence innate immunity and bacterial clearance. Finally, we discuss adaptive immunity against phages and its implications for phage/bacterial interactions. In light of these data, we propose that our microbiome can be understood as an interconnected network of bacteria, bacteriophages, and human cells and that the stability of these tri-kingdom interactions may be important for maintaining our immunologic and metabolic health. Conversely, the disruption of this balance, through exposure to exogenous phages, microbial dysbiosis, or immune dysregulation, may contribute to disease.
MeSH term(s)	Bacteria ; Bacteriophages/genetics ; Humans ; Immune System ; Microbiota ; Viruses
Language	English
Publishing date	2021-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2764224-0
ISSN	2327-0578 ; 2327-056X
ISSN (online)	2327-0578
ISSN	2327-056X
DOI	10.1146/annurev-virology-091919-074551
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Article ; Online: Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.

Barnes, Henry W / Demirdjian, Sally / Haddock, Naomi L / Kaber, Gernot / Martinez, Hunter A / Nagy, Nadine / Karmouty-Quintana, Harry / Bollyky, Paul L

Matrix biology : journal of the International Society for Matrix Biology

2023 Volume 116, Page(s) 49–66

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. Then we briefly summarize the known roles of HA in airway inflammation and immunity. We then address what is known about HA and the pathogenesis of COVID-19 acute respiratory distress syndrome (COVID-19 ARDS). Next, we examine potential roles for HA in post-acute SARS-CoV-2 infection (PASC), also known as "long COVID" as well as in COVID-associated fibrosis. Finally, we discuss the potential therapeutics that target HA as a means to treat COVID-19, including the repurposed drug hymecromone (4-methylumbelliferone). We conclude that HA is a promising potential therapeutic target for the treatment of COVID-19.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Hyaluronic Acid ; Inflammation/pathology ; Post-Acute COVID-19 Syndrome
Chemical Substances	Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2023-02-05
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2023.02.001
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Article ; Online: Phage diversity in cell-free DNA identifies bacterial pathogens in human sepsis cases.

Haddock, Naomi L / Barkal, Layla J / Ram-Mohan, Nikhil / Kaber, Gernot / Chiu, Charles Y / Bhatt, Ami S / Yang, Samuel / Bollyky, Paul L

Nature microbiology

2023 Volume 8, Issue 8, Page(s) 1495–1507

Abstract: Bacteriophages, viruses that infect bacteria, have great specificity for their bacterial hosts at the strain and species level. However, the relationship between the phageome and associated bacterial population dynamics is unclear. Here we generated a ... ...

Abstract	Bacteriophages, viruses that infect bacteria, have great specificity for their bacterial hosts at the strain and species level. However, the relationship between the phageome and associated bacterial population dynamics is unclear. Here we generated a computational pipeline to identify sequences associated with bacteriophages and their bacterial hosts in cell-free DNA from plasma samples. Analysis of two independent cohorts, including a Stanford Cohort of 61 septic patients and 10 controls and the SeqStudy cohort of 224 septic patients and 167 controls, reveals a circulating phageome in the plasma of all sampled individuals. Moreover, infection is associated with overrepresentation of pathogen-specific phages, allowing for identification of bacterial pathogens. We find that information on phage diversity enables identification of the bacteria that produced these phages, including pathovariant strains of Escherichia coli. Phage sequences can likewise be used to distinguish between closely related bacterial species such as Staphylococcus aureus, a frequent pathogen, and coagulase-negative Staphylococcus, a frequent contaminant. Phage cell-free DNA may have utility in studying bacterial infections.
MeSH term(s)	Humans ; Bacteriophages/genetics ; Bacteria/genetics ; Escherichia coli/genetics ; Sepsis
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-023-01406-x
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Article ; Online: Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University.

Würstle, Silvia / Lee, Alina / Kortright, Kaitlyn E / Winzig, Franziska / An, William / Stanley, Gail L / Rajagopalan, Govindarajan / Harris, Zach / Sun, Ying / Hu, Buqu / Blazanin, Michael / Hajfathalian, Maryam / Bollyky, Paul L / Turner, Paul E / Koff, Jonathan L / Chan, Benjamin K

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2657

Abstract: Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d'Hérelle's first publication on the clinical applications of phages. At the Center for ... ...

Abstract	Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d'Hérelle's first publication on the clinical applications of phages. At the Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established to offer safe and potent phages for single-patient investigational new drug applications while recognizing the time constraints imposed by infection(s). This study provides a practical walkthrough of the pipeline with an Autographiviridae phage targeting Pseudomonas aeruginosa (phage vB_PaeA_SB, abbreviated to ΦSB). Notably, a thorough phage characterization and the evolutionary selection pressure exerted on bacteria by phages, analogous to antibiotics, are incorporated into the pipeline.
MeSH term(s)	Humans ; Bacteriophages ; Phage Therapy ; Pseudomonas aeruginosa ; Universities ; Pseudomonas Phages/genetics ; Pseudomonas Infections/therapy ; Pseudomonas Infections/microbiology
Language	English
Publishing date	2024-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52192-3
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Article: The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

Echterhof, Arne / Dharmaraj, Tejas / McBride, Robert / Berry, Joel / Hopkins, Max / Selvakumar, Hemaa / Miesel, Lynn / Chia, Ju-Hsin / Lin, Kun-Yuan / Shen, Chien-Chang / Lee, Yu-Ling / Yeh, Yu-Chuan / Liao, Wei Ting / Suh, Gina / Blankenberg, Francis G / Frymoyer, Adam R / Bollyky, Paul L

bioRxiv : the preprint server for biology

2024

Abstract: With the increasing prevalence of antimicrobial-resistant bacterial infections, there is great interest in using lytic bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage ... ...

Abstract	With the increasing prevalence of antimicrobial-resistant bacterial infections, there is great interest in using lytic bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics
Language	English
Publishing date	2024-01-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.25.577154
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