Compounding Achromobacter Phages for Therapeutic Applications

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

doi:10.3390/v15081665

Open AccessArticle

Compounding Achromobacter Phages for Therapeutic Applications

by

Ana Georgina Cobián Güemes

^1,*

,

Tram Le

¹,

Maria Isabel Rojas

¹

,

Nicole E. Jacobson

¹,

Helena Villela

^1,2,

Katelyn McNair

³

,

Shr-Hau Hung

¹

,

Lili Han

^1,4,

Lance Boling

¹,

Jessica Claire Octavio

¹,

Lorena Dominguez

¹,

Vito Adrian Cantú

³,

Sinéad Archdeacon

⁵

,

Alejandro A. Vega

^1,6

,

Michelle A. An

¹,

Hamza Hajama

¹

,

Gregory Burkeen

¹

,

Robert A. Edwards

^1,3,7

,

Douglas J. Conrad

⁸,

Forest Rohwer

¹ and

Anca M. Segall

^1,3,*

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¹

Department of Biology, Viral Information Institute, San Diego State University, San Diego, CA 92182, USA

²

Marine Microbiomes Lab, Red Sea Research Center, King Abdullah University of Science and Technology, Building 2, Level 3, Room 3216 WS03, Thuwal 23955-6900, Saudi Arabia

³

Computational Sciences Research Center, San Diego State University, San Diego, CA 92182, USA

⁴

Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China

⁵

College of Biological Sciences, University of California Davis, Davis, CA 95616, USA

⁶

David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90025, USA

⁷

Flinders Accelerator for Microbiome Exploration, Flinders University, Sturt Road, Bedford Park 5042, Australia

⁸

Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, San Diego, CA 9500, USA

^*

Authors to whom correspondence should be addressed.

Viruses 2023, 15(8), 1665; https://doi.org/10.3390/v15081665

Submission received: 9 June 2023 / Revised: 27 July 2023 / Accepted: 27 July 2023 / Published: 30 July 2023

(This article belongs to the Special Issue Viruses versus Bacteria—Novel Approaches to Phage Therapy as a Tool against Multidrug-Resistant Pathogens)

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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, thirteen 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.

Keywords: Achromobacter phage; phage therapy; prophage induction; phage production

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MDPI and ACS Style

Cobián Güemes, A.G.; Le, T.; Rojas, M.I.; Jacobson, N.E.; Villela, H.; McNair, K.; Hung, S.-H.; Han, L.; Boling, L.; Octavio, J.C.; et al. Compounding Achromobacter Phages for Therapeutic Applications. Viruses 2023, 15, 1665. https://doi.org/10.3390/v15081665

AMA Style

Cobián Güemes AG, Le T, Rojas MI, Jacobson NE, Villela H, McNair K, Hung S-H, Han L, Boling L, Octavio JC, et al. Compounding Achromobacter Phages for Therapeutic Applications. Viruses. 2023; 15(8):1665. https://doi.org/10.3390/v15081665

Chicago/Turabian Style

Cobián Güemes, Ana Georgina, Tram Le, Maria Isabel Rojas, Nicole E. Jacobson, Helena Villela, Katelyn McNair, Shr-Hau Hung, Lili Han, Lance Boling, Jessica Claire Octavio, and et al. 2023. "Compounding Achromobacter Phages for Therapeutic Applications" Viruses 15, no. 8: 1665. https://doi.org/10.3390/v15081665

APA Style

Cobián Güemes, A. G., Le, T., Rojas, M. I., Jacobson, N. E., Villela, H., 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

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Compounding Achromobacter Phages for Therapeutic Applications

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