Compounding Achromobacter Phages for Therapeutic Applications

Ana Georgina Cobián Cobián Güemes; Tram Le; Maria Isabel Rojas; Nicole Jacobson; Helena Dias Muller Villela; Katelyn McNair; Shr-Hau Hung; Lili Han; Lance Boling; Jessica Claire Octavio; Lorena Dominguez; Vito Adrian Cantú; Sinéad Archdeacon; Alejandro A. Vega; Michelle A. An; Hamza Hajama; Gregory Burkeen; Robert A. Edwards; Douglas J. Conrad; Forest Rohwer; Anca M. Segall

doi:10.3390/v15081665

Compounding Achromobacter Phages for Therapeutic Applications

Ana Georgina Cobián Cobián Güemes, Tram Le, Maria Isabel Rojas, Nicole Jacobson, Helena Dias Muller Villela, Katelyn McNair, Shr-Hau Hung, Lili Han, Lance Boling, Jessica Claire Octavio, Lorena Dominguez, Vito Adrian Cantú, Sinéad Archdeacon, Alejandro A. Vega, Michelle A. An, Hamza Hajama, Gregory Burkeen, Robert A. Edwards, Douglas J. Conrad, Forest RohwerAnca M. Segall

Biological, Environmental Sciences and Engineering

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

3 Scopus citations

Abstract

Achromobacter species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by Achromobacter xylosoxidans CF418 or Achromobacter ruhlandii CF116 experienced fatal exacerbations. Achromobacter spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of Achromobacter. In this study, twelve lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Achromobacter Kumeyaay phage collection. Six distinct Achromobacter phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available Achromobacter phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 Achromobacter clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in Achromobacter xylosoxidans CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as Achromobacter phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 109 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill Achromobacter spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.

Original language	English (US)
Pages (from-to)	1665
Journal	Viruses
Volume	15
Issue number	8
DOIs	https://doi.org/10.3390/v15081665
State	Published - Jul 30 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-08-03
Acknowledgements: This study was funded by the Spruance Foundation and Cystic Fibrosis Research Inc. A.G.C.G. was funded by CONACyT and UCMEXUS. A.M.S. was partially funded by NIDDK grant RC2DK116713. We are grateful to Christine Pourcel, Christiane Essoh, and their colleagues for kindly sharing the Côte d’Ivoire Achromophages collection. We thank Marina Kalyuzhnaya and Dwayne Roach for providing access to lab equipment. We are grateful to Ingrid Niesman, the Director of the SDSU Imaging facility, for the electron micrographs of the SE2 and maay phages. Many thanks to Greg Peters and to Jacob Vander Griend for fruitful discussions during this research, and to Ryan Rowe, for constructing the two transducing donor strains. We are grateful to Margaret Field for revising the meaning of the Kumeyaay words.

ASJC Scopus subject areas

Virology
Infectious Diseases

UN SDGs

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

Access to Document

10.3390/v15081665

https://repository.kaust.edu.sa/bitstream/10754/693389/1/viruses-15-01665-v2.pdf

Cite this

Cobián Güemes, A. G. C., Le, T., Rojas, M. I., Jacobson, N., Villela, H. D. M., McNair, K., Hung, S.-H., Han, L., Boling, L., Octavio, J. C., Dominguez, L., Cantú, V. A., Archdeacon, S., Vega, A. A., An, M. A., Hajama, H., Burkeen, G., Edwards, R. A., Conrad, D. J., ... Segall, A. M. (2023). Compounding Achromobacter Phages for Therapeutic Applications. Viruses, 15(8), 1665. https://doi.org/10.3390/v15081665

@article{ff11644d65db462ab72f7df9593d6b8b,

title = "Compounding Achromobacter Phages for Therapeutic Applications",

abstract = "Achromobacter species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by Achromobacter xylosoxidans CF418 or Achromobacter ruhlandii CF116 experienced fatal exacerbations. Achromobacter spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of Achromobacter. In this study, twelve lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Achromobacter Kumeyaay phage collection. Six distinct Achromobacter phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available Achromobacter phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 Achromobacter clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in Achromobacter xylosoxidans CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as Achromobacter phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 109 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill Achromobacter spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.",

author = "{Cobi{\'a}n G{\"u}emes}, {Ana Georgina Cobi{\'a}n} and Tram Le and Rojas, {Maria Isabel} and Nicole Jacobson and Villela, {Helena Dias Muller} and Katelyn McNair and Shr-Hau Hung and Lili Han and Lance Boling and Octavio, {Jessica Claire} and Lorena Dominguez and Cant{\'u}, {Vito Adrian} and Sin{\'e}ad Archdeacon and Vega, {Alejandro A.} and An, {Michelle A.} and Hamza Hajama and Gregory Burkeen and Edwards, {Robert A.} and Conrad, {Douglas J.} and Forest Rohwer and Segall, {Anca M.}",

note = "KAUST Repository Item: Exported on 2023-08-03 Acknowledgements: This study was funded by the Spruance Foundation and Cystic Fibrosis Research Inc. A.G.C.G. was funded by CONACyT and UCMEXUS. A.M.S. was partially funded by NIDDK grant RC2DK116713. We are grateful to Christine Pourcel, Christiane Essoh, and their colleagues for kindly sharing the C{\^o}te d{\textquoteright}Ivoire Achromophages collection. We thank Marina Kalyuzhnaya and Dwayne Roach for providing access to lab equipment. We are grateful to Ingrid Niesman, the Director of the SDSU Imaging facility, for the electron micrographs of the SE2 and maay phages. Many thanks to Greg Peters and to Jacob Vander Griend for fruitful discussions during this research, and to Ryan Rowe, for constructing the two transducing donor strains. We are grateful to Margaret Field for revising the meaning of the Kumeyaay words.",

year = "2023",

month = jul,

day = "30",

doi = "10.3390/v15081665",

language = "English (US)",

volume = "15",

pages = "1665",

journal = "Viruses",

issn = "1999-4915",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "8",

}

Cobián Güemes, AGC, Le, T, Rojas, MI, Jacobson, N, Villela, HDM, McNair, K, Hung, S-H, Han, L, Boling, L, Octavio, JC, Dominguez, L, Cantú, VA, Archdeacon, S, Vega, AA, An, MA, Hajama, H, Burkeen, G, Edwards, RA, Conrad, DJ, Rohwer, F & Segall, AM 2023, 'Compounding Achromobacter Phages for Therapeutic Applications', Viruses, vol. 15, no. 8, pp. 1665. https://doi.org/10.3390/v15081665

TY - JOUR

T1 - Compounding Achromobacter Phages for Therapeutic Applications

AU - Cobián Güemes, Ana Georgina Cobián

AU - Le, Tram

AU - Rojas, Maria Isabel

AU - Jacobson, Nicole

AU - Villela, Helena Dias Muller

AU - McNair, Katelyn

AU - Hung, Shr-Hau

AU - Han, Lili

AU - Boling, Lance

AU - Octavio, Jessica Claire

AU - Dominguez, Lorena

AU - Cantú, Vito Adrian

AU - Archdeacon, Sinéad

AU - Vega, Alejandro A.

AU - An, Michelle A.

AU - Hajama, Hamza

AU - Burkeen, Gregory

AU - Edwards, Robert A.

AU - Conrad, Douglas J.

AU - Rohwer, Forest

AU - Segall, Anca M.

N1 - KAUST Repository Item: Exported on 2023-08-03 Acknowledgements: This study was funded by the Spruance Foundation and Cystic Fibrosis Research Inc. A.G.C.G. was funded by CONACyT and UCMEXUS. A.M.S. was partially funded by NIDDK grant RC2DK116713. We are grateful to Christine Pourcel, Christiane Essoh, and their colleagues for kindly sharing the Côte d’Ivoire Achromophages collection. We thank Marina Kalyuzhnaya and Dwayne Roach for providing access to lab equipment. We are grateful to Ingrid Niesman, the Director of the SDSU Imaging facility, for the electron micrographs of the SE2 and maay phages. Many thanks to Greg Peters and to Jacob Vander Griend for fruitful discussions during this research, and to Ryan Rowe, for constructing the two transducing donor strains. We are grateful to Margaret Field for revising the meaning of the Kumeyaay words.

PY - 2023/7/30

Y1 - 2023/7/30

N2 - Achromobacter species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by Achromobacter xylosoxidans CF418 or Achromobacter ruhlandii CF116 experienced fatal exacerbations. Achromobacter spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of Achromobacter. In this study, twelve lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Achromobacter Kumeyaay phage collection. Six distinct Achromobacter phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available Achromobacter phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 Achromobacter clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in Achromobacter xylosoxidans CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as Achromobacter phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 109 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill Achromobacter spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.

AB - Achromobacter species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by Achromobacter xylosoxidans CF418 or Achromobacter ruhlandii CF116 experienced fatal exacerbations. Achromobacter spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of Achromobacter. In this study, twelve lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Achromobacter Kumeyaay phage collection. Six distinct Achromobacter phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available Achromobacter phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 Achromobacter clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in Achromobacter xylosoxidans CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as Achromobacter phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 109 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill Achromobacter spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.

UR - http://hdl.handle.net/10754/693389

UR - https://www.mdpi.com/1999-4915/15/8/1665

U2 - 10.3390/v15081665

DO - 10.3390/v15081665

M3 - Article

C2 - 37632008

SN - 1999-4915

VL - 15

SP - 1665

JO - Viruses

JF - Viruses

IS - 8

ER -

Compounding Achromobacter Phages for Therapeutic Applications

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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