A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica

ABSTRACT Photorhabdus is a bacterial genus containing both insect and emerging human pathogens. Most insect-restricted species display temperature restriction, unable to grow above 34°C, while Photorhabdus asymbiotica can grow at 37°C to infect mammalian hosts and cause Photorhabdosis. Metabolic ada...

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Main Authors: Elena Lucy Carter, Nicholas R. Waterfield, Chrystala Constantinidou, Mohammad Tauqeer Alam
Format: Article
Language:English
Published: American Society for Microbiology 2024-11-01
Series:mSystems
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Online Access:https://journals.asm.org/doi/10.1128/msystems.00970-23
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author Elena Lucy Carter
Nicholas R. Waterfield
Chrystala Constantinidou
Mohammad Tauqeer Alam
author_facet Elena Lucy Carter
Nicholas R. Waterfield
Chrystala Constantinidou
Mohammad Tauqeer Alam
author_sort Elena Lucy Carter
collection DOAJ
description ABSTRACT Photorhabdus is a bacterial genus containing both insect and emerging human pathogens. Most insect-restricted species display temperature restriction, unable to grow above 34°C, while Photorhabdus asymbiotica can grow at 37°C to infect mammalian hosts and cause Photorhabdosis. Metabolic adaptations have been proposed to facilitate the survival of this pathogen at higher temperatures, yet the biological mechanisms underlying these are poorly understood. We have reconstructed an extensively manually curated genome-scale metabolic model of P. asymbiotica (iEC1073, BioModels ID MODEL2309110001), validated through in silico gene knockout and nutrient utilization experiments with an excellent agreement between experimental data and model predictions. Integration of iEC1073 with transcriptomics data obtained for P. asymbiotica at temperatures of 28°C and 37°C allowed the development of temperature-specific reconstructions representing metabolic adaptations the pathogen undergoes when shifting to a higher temperature in a mammalian compared to insect host. Analysis of these temperature-specific reconstructions reveals that nucleotide metabolism is enriched with predicted upregulated and downregulated reactions. iEC1073 could be used as a powerful tool to study the metabolism of P. asymbiotica, in different genetic or environmental conditions.IMPORTANCEPhotorhabdus bacterial species contain both human and insect pathogens, and most of these species cannot grow in higher temperatures. However, Photorhabdus asymbiotica, which infects both humans and insects, can grow in higher temperatures and undergoes metabolic adaptations at a temperature of 37°C compared to that of insect body temperature. Therefore, it is important to examine how this bacterial species can metabolically adapt to survive in higher temperatures. In this work, using a mathematical model, we have examined the metabolic shift that takes place when the bacteria switch from growth conditions in 28°C to 37°C. We show that P. asymbiotica potentially experiences predicted temperature-induced metabolic adaptations at 37°C predominantly clustered within the nucleotide metabolism pathway.
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spelling doaj-art-0a95af45a2954883ac91c76c21fd743c2024-12-25T12:35:40ZengAmerican Society for MicrobiologymSystems2379-50772024-11-0191110.1128/msystems.00970-23A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbioticaElena Lucy Carter0Nicholas R. Waterfield1Chrystala Constantinidou2Mohammad Tauqeer Alam3Warwick Medical School, University of Warwick, Gibbet Hill Campus, Coventry, United KingdomWarwick Medical School, University of Warwick, Gibbet Hill Campus, Coventry, United KingdomWarwick Medical School, University of Warwick, Gibbet Hill Campus, Coventry, United KingdomDepartment of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab EmiratesABSTRACT Photorhabdus is a bacterial genus containing both insect and emerging human pathogens. Most insect-restricted species display temperature restriction, unable to grow above 34°C, while Photorhabdus asymbiotica can grow at 37°C to infect mammalian hosts and cause Photorhabdosis. Metabolic adaptations have been proposed to facilitate the survival of this pathogen at higher temperatures, yet the biological mechanisms underlying these are poorly understood. We have reconstructed an extensively manually curated genome-scale metabolic model of P. asymbiotica (iEC1073, BioModels ID MODEL2309110001), validated through in silico gene knockout and nutrient utilization experiments with an excellent agreement between experimental data and model predictions. Integration of iEC1073 with transcriptomics data obtained for P. asymbiotica at temperatures of 28°C and 37°C allowed the development of temperature-specific reconstructions representing metabolic adaptations the pathogen undergoes when shifting to a higher temperature in a mammalian compared to insect host. Analysis of these temperature-specific reconstructions reveals that nucleotide metabolism is enriched with predicted upregulated and downregulated reactions. iEC1073 could be used as a powerful tool to study the metabolism of P. asymbiotica, in different genetic or environmental conditions.IMPORTANCEPhotorhabdus bacterial species contain both human and insect pathogens, and most of these species cannot grow in higher temperatures. However, Photorhabdus asymbiotica, which infects both humans and insects, can grow in higher temperatures and undergoes metabolic adaptations at a temperature of 37°C compared to that of insect body temperature. Therefore, it is important to examine how this bacterial species can metabolically adapt to survive in higher temperatures. In this work, using a mathematical model, we have examined the metabolic shift that takes place when the bacteria switch from growth conditions in 28°C to 37°C. We show that P. asymbiotica potentially experiences predicted temperature-induced metabolic adaptations at 37°C predominantly clustered within the nucleotide metabolism pathway.https://journals.asm.org/doi/10.1128/msystems.00970-23metabolic modelingflux balance analysisgenome scale modelPhotorhabdusstress adaptation
spellingShingle Elena Lucy Carter
Nicholas R. Waterfield
Chrystala Constantinidou
Mohammad Tauqeer Alam
A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica
mSystems
metabolic modeling
flux balance analysis
genome scale model
Photorhabdus
stress adaptation
title A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica
title_full A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica
title_fullStr A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica
title_full_unstemmed A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica
title_short A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica
title_sort temperature induced metabolic shift in the emerging human pathogen photorhabdus asymbiotica
topic metabolic modeling
flux balance analysis
genome scale model
Photorhabdus
stress adaptation
url https://journals.asm.org/doi/10.1128/msystems.00970-23
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