The role of host molecules in communication with the resident and pathogenic microbiota: A review

White, Joni Renee; Dauros-Singorenko, Priscila; Hong, Jiwon; Vanholsbeeck, Frédérique; Phillips, Anthony R.J.; Swift, Simon

doi:10.1016/j.medmic.2020.100005

Cited by 19 publications

(14 citation statements)

References 108 publications

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“…For example, where EVs stabilise bioactive molecules, such as RNAs, they may enable more efficient delivery to bacteria, and effect non-lethal control of microbial behaviour [ 99 ]. To this end, we have previously reviewed host molecules that may contribute to changes in the resident and pathogenic microbiota [ 100 ], and here we highlight the role that EVs may play in connecting these molecules with bacteria.…”

Section: Host Ev-mediated Response To Infectionmentioning

confidence: 99%

The complex, bidirectional role of extracellular vesicles in infection

White

Dauros-Singorenko

Hong

et al. 2021

Biochemical Society Transactions

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Cells from all domains of life release extracellular vesicles (EVs), packages that carry a cargo of molecules that participate in communication, co-ordination of population behaviours, virulence and immune response mechanisms. Mammalian EVs play an increasingly recognised role to fight infection, yet may also be commandeered to disseminate pathogens and enhance infection. EVs released by bacterial pathogens may deliver toxins to host cells, signalling molecules and new DNA to other bacteria, and act as decoys, protecting infecting bacteria from immune killing. In this review, we explore the role of EVs in infection from the perspective of both the pathogen and host, and highlight their importance in the host/pathogen relationship. We highlight proposed strategies for EVs in therapeutics, and call attention to areas where existing knowledge and evidence is lacking.

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Section: Host Ev-mediated Response To Infectionmentioning

confidence: 99%

The complex, bidirectional role of extracellular vesicles in infection

White

Dauros-Singorenko

Hong

et al. 2021

Biochemical Society Transactions

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“…In general terms, the adaption of P. aeruginosa CYP168A1 to metabolize arachidonic acid to 18-, 19-, and nominally 20-HETE may reflect a burgeoning ability of the pathogen to modulate the immune response of the host organism in order to make the lung environment more palatable for colonization. A hallmark of pathogen success as a parasite is the ability for it be able to “communicate” with the host organism through the production of proteins and small molecule metabolites that have the ability to modulate the immune response and/or improve the characteristics of the host environment in order to permit pathogen growth and replication (109, 110). P. aeruginosa may accomplish this through its metabolism of arachidonic acid to metabolites, such as 18-, 19,- and 20-HETE, that provide important physiological functions.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosacytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE

Tooker

Kandel

Work

et al. 2021

Preprint

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Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen that is highly prevalent in individuals with cystic fibrosis (CF). A major problem in treating CF patients infected with P. aeruginosa is the development of antibiotic resistance. Therefore, the identification of novel P. aeruginosa antibiotic drug targets is of the upmost urgency. The genome of P. aeruginosa contains four putative cytochrome P450 enzymes (CYPs) of unknown function that have never before been characterized. Analogous to some of the CYPs from M. tuberculosis, the P. aeruginosa CYPs may be important for growth and colonization of the CF patient’s lung. In this study, we cloned, expressed, and characterized CYP168A1 from P. aeruginosa and identified it as a sub-terminal fatty acid hydroxylase. Spectral binding data and computational modeling of substrates and inhibitors suggest that CYP168A1 has a large, expansive active site preferring long chain fatty acids and large hydrophobic inhibitors. Furthermore, metabolism experiments confirm that the enzyme is capable of hydroxylating arachidonic acid, an important inflammatory signaling molecule present in abundance in the CF lung, to 19-hydroxyeicosatetraenoic acid (19-HETE; Km = 41.1 µM, Vmax = 222 pmol/min/nmol P450), a potent vasoconstrictor which may play a role in the pathogen’s ability to colonize the mammalian lung. Metabolism of arachidonic acid is subject to substrate inhibition and is also inhibited by the presence of ketoconazole. This study points to the discovery of a new potential drug target that may be of utility in treating drug resistant P. aeruginosa.

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“…Evidence from animal and human studies depict that the host exercises control over the population of gut microbiota, through many host molecules such as microRNA, hormones, cytokines and metabolites, which interact with the microbiome and induce alterations in the growth or behavior of bacteria [ 38 ]. Many of these molecules have been shown to interact directly with the microorganisms.…”

Section: Gut Microbiota and Its Close Relationship To Dietmentioning

confidence: 99%

“…Many of these molecules have been shown to interact directly with the microorganisms. Extracellular vesicles are proposed to help to carry these molecules to bacteria for increased uptake [ 38 ].…”

Section: Gut Microbiota and Its Close Relationship To Dietmentioning

confidence: 99%

Gut microbiome and Mediterranean diet in the context of obesity. Current knowledge, perspectives and potential therapeutic targets

et al. 2021

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Mediterranean Diet has been recognized as one of the healthiest and sustainable dietary patterns worldwide, based on the food habits of people living in the Mediterranean region. It is focused on a plant-based cuisine combining local agricultural products and moderate intake of fish. As eating habits seem to exert a major impact on the composition of gut microbiota, numerous studies show that an adherence to the Mediterranean diet positively influences the microbiome ecosystem network. This has a profound effect on multiple host metabolic pathways and plays a major role in immune and metabolic homeostasis. Among metabolic disorders, obesity represents a major health issue where Mediterranean Dietary regime could possibly slowdown its spread. The aim of this review is to emphasize the interaction between diet and gut microbiota and the potential beneficial effects of Mediterranean diet on metabolic disorders like obesity, which is responsible for the development of many noncommunicable diseases.

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The role of host molecules in communication with the resident and pathogenic microbiota: A review

Cited by 19 publications

References 108 publications

The complex, bidirectional role of extracellular vesicles in infection

The complex, bidirectional role of extracellular vesicles in infection

Pseudomonas aeruginosacytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE

Gut microbiome and Mediterranean diet in the context of obesity. Current knowledge, perspectives and potential therapeutic targets

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