Bacteriophage Adaptation to a Mammalian Mucosa Reveals a Trans-Domain Evolutionary Axis

Chin, Wai Hoe; Kett, Ciaren; Cooper, Oren; Müseler, Deike; Zhang, Yaqi; Bamert, Rebecca S.; Patwa, Ruzeen; Woods, Laura C.; Devendran, Citsabehsan; Tiralongo, Joe; Lithgow, Trevor; McDonald, Michael J.; Neild, Adrian; Barr, Jeremy J.

doi:10.2139/ssrn.3871902

Cited by 2 publications

(3 citation statements)

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“…Moreover, the diversity and plasticity of the phage genome can also improve phage adaptability to GI sites and form niches in the mammalian gut environment. In a guton-a-chip mucosal environment, evolved phage populations, particularly those with a genetic mutation on phage capsid protein, could cause the altered glycan-binding phenotype, showing a competitive fitness advantage over ancestral phages [29]. Specifically, phages with mutated phage capsid protein Hoc facilitate phage adherence to mucus via binding to human fucosylated mucin glycans and are further localized toward bacterial hosts [29].…”

Section: Phages In the Mammalian Gutmentioning

confidence: 99%

“…In a guton-a-chip mucosal environment, evolved phage populations, particularly those with a genetic mutation on phage capsid protein, could cause the altered glycan-binding phenotype, showing a competitive fitness advantage over ancestral phages [29]. Specifically, phages with mutated phage capsid protein Hoc facilitate phage adherence to mucus via binding to human fucosylated mucin glycans and are further localized toward bacterial hosts [29]. Additionally, compared to the control group (phage-bacterial co-evolution without a mammalian mucosal environment), increasing phage variations with distinct gene mutational profiles were observed in the group with a mammalian mucosal environment.…”

Section: Phages In the Mammalian Gutmentioning

confidence: 99%

“…Additionally, compared to the control group (phage-bacterial co-evolution without a mammalian mucosal environment), increasing phage variations with distinct gene mutational profiles were observed in the group with a mammalian mucosal environment. The evolution of these phages in response to the dynamic mammalian gut environment demonstrates a trans-domain evolutionary process along the phage-mammalian axis [29]. Similarly, the tail fiber genes encoding proteins in some phages can bind to human heparansulfated proteoglycans and later place phages near the epithelial cell surface, facilitating contact with bacterial hosts and infection [30].…”

Section: Phages In the Mammalian Gutmentioning

confidence: 99%

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Gut Phageome—An Insight into the Role and Impact of Gut Microbiome and Their Correlation with Mammal Health and Diseases

Zhang,

Sharma,

Tom

et al. 2023

Microorganisms

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The gut microbiota, including bacteria, archaea, fungi, and viruses, compose a diverse mammalian gut environment and are highly associated with host health. Bacteriophages, the viruses that infect bacteria, are the primary members of the gastrointestinal virome, known as the phageome. However, our knowledge regarding the gut phageome remains poorly understood. In this review, the critical role of the gut phageome and its correlation with mammalian health were summarized. First, an overall profile of phages across the gastrointestinal tract and their dynamic roles in shaping the surrounding microorganisms was elucidated. Further, the impacts of the gut phageome on gastrointestinal fitness and the bacterial community were highlighted, together with the influence of diets on the gut phageome composition. Additionally, new reports on the role of the gut phageome in the association of mammalian health and diseases were reviewed. Finally, a comprehensive update regarding the advanced phage benchwork and contributions of phage-based therapy to prevent/treat mammalian diseases was provided. This study provides insights into the role and impact of the gut phagenome in gut environments closely related to mammal health and diseases. The findings provoke the potential applications of phage-based diagnosis and therapy in clinical and agricultural fields. Future research is needed to uncover the underlying mechanism of phage–bacterial interactions in gut environments and explore the maintenance of mammalian health via phage-regulated gut microbiota.

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Section: Phages In the Mammalian Gutmentioning

confidence: 99%

Section: Phages In the Mammalian Gutmentioning

confidence: 99%

Section: Phages In the Mammalian Gutmentioning

confidence: 99%

See 1 more Smart Citation

Gut Phageome—An Insight into the Role and Impact of Gut Microbiome and Their Correlation with Mammal Health and Diseases

Zhang,

Sharma,

Tom

et al. 2023

Microorganisms

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Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

2023

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For those born with cystic fibrosis (CF), hyper-concentrated mucus with a dysfunctional structure significantly impacts CF airways, providing a perfect environment for bacterial colonization and subsequent chronic infection. Early treatment with antibiotics limits the prevalence of bacterial pathogens but permanently alters the CF airway microenvironment, resulting in antibiotic resistance and other long-term consequences. With little investment into new traditional antibiotics, safe and effective alternative therapeutic options are urgently needed. One gathering significant traction is bacteriophage (phage) therapy. However, little is known about which phages are effective for respiratory infections, the dynamics involved between phage(s) and the host airway, and associated by-products, including mucus. Work utilizing gut cell models suggest that phages adhere to mucus components, reducing microbial colonization and providing non-host-derived immune protection. Thus, phages retained in the CF mucus layer result from the positive selection that enables them to remain in the mucus layer. Phages bind weakly to mucus components, slowing down the diffusion motion and increasing their chance of encountering bacterial species for subsequent infection. Adherence of phage to mucus could also facilitate phage enrichment and persistence within the microenvironment, resulting in a potent phage phenotype or vice versa. However, how the CF microenvironment responds to phage and impacts phage functionality remains unknown. This review discusses CF associated lung diseases, the impact of CF mucus, and chronic bacterial infection. It then discusses the therapeutic potential of phages, their dynamic relationship with mucus and whether this may enhance or hinder airway bacterial infections in CF.

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Bacteriophage Adaptation to a Mammalian Mucosa Reveals a Trans-Domain Evolutionary Axis

Cited by 2 publications

References 0 publications

Gut Phageome—An Insight into the Role and Impact of Gut Microbiome and Their Correlation with Mammal Health and Diseases

Gut Phageome—An Insight into the Role and Impact of Gut Microbiome and Their Correlation with Mammal Health and Diseases

Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

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