Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

Michelle S. Bach; Christiaan R. de Vries; Arya Khosravi; Johanna M. Sweere; Medeea C. Popescu; Qingquan Chen; Sally Demirdjian; Aviv Hargil; Jonas D. Van Belleghem; Gernot Kaber; Maryam Hajfathalian; Elizabeth B. Burgener; Dan Liu; Quynh Lam Tran; Tejas Dharmaraj; Maria Birukova; Vivekananda Sunkari; Swathi Balaji; Nandini Ghosh; Shomita S. Mathew-Steiner; Mohamed S. El Masry; Sundeep G. Keswani; Niaz Banaei; Laurence Nedelec; Chandan K. Sen; Venita Chandra; Patrick R. Secor; Gina A. Suh; Paul L. Bollyky

doi:10.1016/j.xcrm.2022.100656

Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

Michelle S. Bach
, Christiaan R. de Vries
, Arya Khosravi
, Johanna M. Sweere
, Medeea C. Popescu
, Qingquan Chen
, Sally Demirdjian
, Aviv Hargil
, Jonas D. Van Belleghem
, Gernot Kaber
, Maryam Hajfathalian
, Elizabeth B. Burgener
, Dan Liu
, Quynh Lam Tran
, Tejas Dharmaraj
, Maria Birukova
, Vivekananda Sunkari
, Swathi Balaji
, Nandini Ghosh
, Shomita S. Mathew-Steiner

Mohamed S. El Masry, Sundeep G. Keswani, Niaz Banaei, Laurence Nedelec, Chandan K. Sen, Venita Chandra, Patrick R. Secor, Gina A. Suh, Paul L. Bollyky

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.

Original language	English
Article number	100656
Journal	Cell Reports Medicine
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2022.100656
State	Published - Jun 21 2022

Funding

M.S.B. was supported by the Stanford Bio-X Fellowship. C.R.d.V. was supported by grant T32 AI007502 , Doris Duke Physician Scientist Fellowship, and K08AI151089 . A.K. was supported by grant T32 AI007502 . J.M.S. was supported by the Gabilan Stanford Graduate Fellowship for Science and Engineering and the Lubert Stryer Bio-X Stanford Interdisciplinary Graduate Fellowship. M.H. was supported by funding from NIH grant 1K99EB028838-01A1 . P.L.B. was supported by grants R21AI133370 , R21AI133240 , and R01AI12492093 , and grants from Stanford SPARK , the Falk Medical Research Trust , and the Cystic Fibrosis Foundation (CFF).

Funder number
R01AI12492093, 1K99EB028838-01A1, R21AI133240
R21AI133370

Keywords

Pf
Pseudomonas
bacteriophage
filamentous phage
immunology
microbiology
wounds

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xcrm.2022.100656

Cite this

Bach, M. S., de Vries, C. R., Khosravi, A., Sweere, J. M., Popescu, M. C., Chen, Q., Demirdjian, S., Hargil, A., Van Belleghem, J. D., Kaber, G., Hajfathalian, M., Burgener, E. B., Liu, D., Tran, Q. L., Dharmaraj, T., Birukova, M., Sunkari, V., Balaji, S., Ghosh, N., ... Bollyky, P. L. (2022). Filamentous bacteriophage delays healing of Pseudomonas-infected wounds. Cell Reports Medicine, 3(6), Article 100656. https://doi.org/10.1016/j.xcrm.2022.100656

@article{6c0ac57ac1624ced9b7dfb192c12fd33,

title = "Filamentous bacteriophage delays healing of Pseudomonas-infected wounds",

abstract = "Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.",

keywords = "Pf, Pseudomonas, bacteriophage, filamentous phage, immunology, microbiology, wounds",

author = "Bach, \{Michelle S.\} and \{de Vries\}, \{Christiaan R.\} and Arya Khosravi and Sweere, \{Johanna M.\} and Popescu, \{Medeea C.\} and Qingquan Chen and Sally Demirdjian and Aviv Hargil and \{Van Belleghem\}, \{Jonas D.\} and Gernot Kaber and Maryam Hajfathalian and Burgener, \{Elizabeth B.\} and Dan Liu and Tran, \{Quynh Lam\} and Tejas Dharmaraj and Maria Birukova and Vivekananda Sunkari and Swathi Balaji and Nandini Ghosh and Mathew-Steiner, \{Shomita S.\} and \{El Masry\}, \{Mohamed S.\} and Keswani, \{Sundeep G.\} and Niaz Banaei and Laurence Nedelec and Sen, \{Chandan K.\} and Venita Chandra and Secor, \{Patrick R.\} and Suh, \{Gina A.\} and Bollyky, \{Paul L.\}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = jun,

day = "21",

doi = "10.1016/j.xcrm.2022.100656",

language = "English",

volume = "3",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "6",

}

Bach, MS, de Vries, CR, Khosravi, A, Sweere, JM, Popescu, MC, Chen, Q, Demirdjian, S, Hargil, A, Van Belleghem, JD, Kaber, G, Hajfathalian, M, Burgener, EB, Liu, D, Tran, QL, Dharmaraj, T, Birukova, M, Sunkari, V, Balaji, S, Ghosh, N, Mathew-Steiner, SS, El Masry, MS, Keswani, SG, Banaei, N, Nedelec, L, Sen, CK, Chandra, V, Secor, PR, Suh, GA & Bollyky, PL 2022, 'Filamentous bacteriophage delays healing of Pseudomonas-infected wounds', Cell Reports Medicine, vol. 3, no. 6, 100656. https://doi.org/10.1016/j.xcrm.2022.100656

TY - JOUR

T1 - Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

AU - Bach, Michelle S.

AU - de Vries, Christiaan R.

AU - Khosravi, Arya

AU - Sweere, Johanna M.

AU - Popescu, Medeea C.

AU - Chen, Qingquan

AU - Demirdjian, Sally

AU - Hargil, Aviv

AU - Van Belleghem, Jonas D.

AU - Kaber, Gernot

AU - Hajfathalian, Maryam

AU - Burgener, Elizabeth B.

AU - Liu, Dan

AU - Tran, Quynh Lam

AU - Dharmaraj, Tejas

AU - Birukova, Maria

AU - Sunkari, Vivekananda

AU - Balaji, Swathi

AU - Ghosh, Nandini

AU - Mathew-Steiner, Shomita S.

AU - El Masry, Mohamed S.

AU - Keswani, Sundeep G.

AU - Banaei, Niaz

AU - Nedelec, Laurence

AU - Sen, Chandan K.

AU - Chandra, Venita

AU - Secor, Patrick R.

AU - Suh, Gina A.

AU - Bollyky, Paul L.

PY - 2022/6/21

Y1 - 2022/6/21

N2 - Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.

AB - Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.

KW - Pf

KW - Pseudomonas

KW - bacteriophage

KW - filamentous phage

KW - immunology

KW - microbiology

KW - wounds

UR - https://www.scopus.com/pages/publications/85132620076

U2 - 10.1016/j.xcrm.2022.100656

DO - 10.1016/j.xcrm.2022.100656

M3 - Article

C2 - 35732145

AN - SCOPUS:85132620076

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 6

M1 - 100656

ER -

Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

Abstract

Funding

Keywords

UN SDGs

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