Phage-based target discovery and its exploitation towards novel antibacterial molecules

Wan, Xing; Hendrix, Hanne; Skurnik, Mikael; Lavigne, Rob

doi:10.1016/j.copbio.2020.08.015

Cited by 23 publications

(14 citation statements)

References 47 publications

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“…The high cell density, continuous inflow of nutrients, stable temperature, moisture, conjugation opportunities, and biofilm structures set the stage for signal transmission and communication, and provide excellent opportunities for phage evolution, predation, replication, and survival [27,28]. Phages are neglected human pathogens that hijack the metabolic system of bacteria to propagate [29,30], thereby significantly altering certain bacterial populations in the gut and indirectly contributing to the shift from health to disease in mammals [31,32]. However, there are few reports on the mechanisms of phage homeostasis maintenance.…”

Section: Discussionmentioning

confidence: 99%

Autoinducer‐2‐mediated quorum‐sensing system resists T4 phage infection in Escherichia coli

et al. 2021

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In response to the restriction of nutrients and predation by natural enemies, bacteria have evolved complex coping strategies to ensure the reproduction and survival of individual species. Quorum sensing (QS) is involved in the bacterial response to phage predation and regulation of cellular metabolism. However, to date, no clear evidence exists regarding the involvement of autoinducer‐2 (AI‐2)‐mediated QS systems in Escherichia coli in response to the challenges of nutrient restriction and phage infection. In this study, the role of the AI‐2‐mediated QS system in resisting T4 phage infection and regulating cell mechanisms in E. coli was revealed for the first time. This effect of the AI‐2‐mediated QS was achieved by simultaneously downregulating the T4 absorption site and carbon and glucose metabolism. Additionally, we found that lsrB, a metabolic brake, participates in AI‐2‐mediated regulation and maintenance of the normal metabolic balance of cells. The novel phage defense strategy and regulation and maintenance of cellular metabolism effectively limited the expansion of the phage population.

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Section: Discussionmentioning

confidence: 99%

Autoinducer‐2‐mediated quorum‐sensing system resists T4 phage infection in Escherichia coli

et al. 2021

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“…However, care must be taken to ensure that hypothetical proteins chosen for removal do not negatively affect phage fitness. Additionally, phage hypothetical proteins encoded by early genes significantly affect host metabolism during phage infection and may have bactericidal effects upon overexpression, demonstrating an untapped source of inspiration for novel antimicrobial molecules with specific narrow spectrum bacterial targets [190,191].…”

Section: Perspectives and Future Directionsmentioning

confidence: 99%

The Potential of Phage Therapy against the Emerging Opportunistic Pathogen Stenotrophomonas maltophilia

McCutcheon

Dennis

2021

Viruses

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The isolation and characterization of bacteriophages for the treatment of infections caused by the multidrug resistant pathogen Stenotrophomonas maltophilia is imperative as nosocomial and community-acquired infections are rapidly increasing in prevalence. This increase is largely due to the numerous virulence factors and antimicrobial resistance genes encoded by this bacterium. Research on S. maltophilia phages to date has focused on the isolation and in vitro characterization of novel phages, often including genomic characterization, from the environment or by induction from bacterial strains. This review summarizes the clinical significance, virulence factors, and antimicrobial resistance mechanisms of S. maltophilia, as well as all phages isolated and characterized to date and strategies for their use. We further address the limited in vivo phage therapy studies conducted against this bacterium and discuss the future research needed to spearhead phages as an alternative treatment option against multidrug resistant S. maltophilia.

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“…In addition to phage enzyme-based antimicrobials and phage therapy, advancements in genome-driven screening, annotation, and interaction modelling have improved our understanding of hypothetical proteins with once unknown function. These small and early genes have been targeted for their potential as novel polypeptides with bactericidal properties [327]. Phage-based hijacking proteins and mechanisms may be suitable in either uncovering new targets for existing antibacterial agents or for novel antimicrobials altogether [327].…”

Section: Future Perspectives and Applications Of Bacteriophages In Thmentioning

confidence: 99%

“…These small and early genes have been targeted for their potential as novel polypeptides with bactericidal properties [327]. Phage-based hijacking proteins and mechanisms may be suitable in either uncovering new targets for existing antibacterial agents or for novel antimicrobials altogether [327]. Furthermore, while current studies exploring phage-based therapeutics may focus on a traditional approach in directly killing bacterial cells or inhibiting their growth, new phage-based antivirulence strategies may aim to disarm bacterial pathogens and render them less virulent or more susceptible to other avenues of removal [244].…”

Section: Future Perspectives and Applications Of Bacteriophages In Thmentioning

confidence: 99%

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

et al. 2021

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Extended overuse and misuse of antibiotics and other antibacterial agents has resulted in an antimicrobial resistance crisis. Bacteriophages, viruses that infect bacteria, have emerged as a legitimate alternative antibacterial agent with a wide scope of applications which continue to be discovered and refined. However, the potential of some bacteriophages to aid in the acquisition, maintenance, and dissemination of negatively associated bacterial genes, including resistance and virulence genes, through transduction is of concern and requires deeper understanding in order to be properly addressed. In particular, their ability to interact with mobile genetic elements such as plasmids, genomic islands, and integrative conjugative elements (ICEs) enables bacteriophages to contribute greatly to bacterial evolution. Nonetheless, bacteriophages have the potential to be used as therapeutic and biocontrol agents within medical, agricultural, and food processing settings, against bacteria in both planktonic and biofilm environments. Additionally, bacteriophages have been deployed in developing rapid, sensitive, and specific biosensors for various bacterial targets. Intriguingly, their bioengineering capabilities show great promise in improving their adaptability and effectiveness as biocontrol and detection tools. This review aims to provide a balanced perspective on bacteriophages by outlining advantages, challenges, and future steps needed in order to boost their therapeutic and biocontrol potential, while also providing insight on their potential role in contributing to bacterial evolution and survival.

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Phage-based target discovery and its exploitation towards novel antibacterial molecules

Cited by 23 publications

References 47 publications

Autoinducer‐2‐mediated quorum‐sensing system resists T4 phage infection in Escherichia coli

Autoinducer‐2‐mediated quorum‐sensing system resists T4 phage infection in Escherichia coli

The Potential of Phage Therapy against the Emerging Opportunistic Pathogen Stenotrophomonas maltophilia

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

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