Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

Irene Rodriguez-Arce; Tamim Al-Jubair; Begona Euba; Ariadna Fernandez-Calvet; Celia Gil-Campillo; Sara Marti; Susanna Tornroth-Horsefield; Kristian Riesbeck; Junkal Garmendia

doi:10.1080/21505594.2019.1596506

Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

Irene Rodriguez-Arce, Tamim Al-Jubair, Begona Euba, Ariadna Fernandez-Calvet, Celia Gil-Campillo, Sara Marti, Susanna Tornroth-Horsefield, Kristian Riesbeck, Junkal Garmendia

Inflammation, Metabolism and Oxidation

7 Citations (Scopus)

1 Downloads (Pure)

Abstract

Nutrient iron sequestration is the most significant form of nutritional immunity and causes bacterial pathogens to evolve strategies of host iron scavenging. Cigarette smoking contains iron particulates altering lung and systemic iron homeostasis, which may enhance colonization in the lungs of patients suffering chronic obstructive pulmonary disease (COPD) by opportunistic pathogens such as nontypeable. NTHi is a heme auxotroph, and the NTHi genome contains multiple heme acquisition systems whose role in pulmonary infection requires a global understanding. In this study, we determined the relative contribution to NTHi airway infection of the four heme-acquisition systems HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF that are located at the bacterial outer membrane or the periplasm. Our computational studies provided plausible 3D models for HbpA, SapA, PE, and HxuA interactions with heme. Generation and characterization of single mutants in the hxuCBA, hpe, sapA, and hbpA genes provided evidence for participation in heme binding-storage and inter-bacterial donation. The hxuA, sapA, hbpA, and hpe genes showed differential expression and responded to heme. Moreover, HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF presented moonlighting properties related to resistance to antimicrobial peptides or glutathione import, together likely contributing to the NTHi-host airway interplay, as observed upon cultured airway epithelia and in vivo lung infection. The observed multi-functionality was shown to be system-specific, thus limiting redundancy. Together, we provide evidence for heme uptake systems as bacterial factors that act in a coordinated and multi-functional manner to subvert nutritional- and other sources of host innate immunity during NTHi airway infection.

Original language	English
Journal	Virulence
Volume	10
Issue number	1
Pages (from-to)	315-333
ISSN	2150-5594
DOIs	https://doi.org/10.1080/21505594.2019.1596506
Publication status	Published - 1 Jan 2019

Keywords

Haemophilus influenzae
heme binding
iron nutritional immunity
protein moonlighting
respiratory infection

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10.1080/21505594.2019.1596506

OA-Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway pathogen interplay in a coordinated mannerFinal published version, 2.93 MBLicence: CC BY

Cite this

Rodriguez-Arce, I., Al-Jubair, T., Euba, B., Fernandez-Calvet, A., Gil-Campillo, C., Marti, S., Tornroth-Horsefield, S., Riesbeck, K., & Garmendia, J. (2019). Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner. Virulence, 10(1), 315-333. https://doi.org/10.1080/21505594.2019.1596506

Rodriguez-Arce, I, Al-Jubair, T, Euba, B, Fernandez-Calvet, A, Gil-Campillo, C, Marti, S, Tornroth-Horsefield, S, Riesbeck, K & Garmendia, J 2019, 'Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner', Virulence, vol. 10, no. 1, pp. 315-333. https://doi.org/10.1080/21505594.2019.1596506

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abstract = "Nutrient iron sequestration is the most significant form of nutritional immunity and causes bacterial pathogens to evolve strategies of host iron scavenging. Cigarette smoking contains iron particulates altering lung and systemic iron homeostasis, which may enhance colonization in the lungs of patients suffering chronic obstructive pulmonary disease (COPD) by opportunistic pathogens such as nontypeable. NTHi is a heme auxotroph, and the NTHi genome contains multiple heme acquisition systems whose role in pulmonary infection requires a global understanding. In this study, we determined the relative contribution to NTHi airway infection of the four heme-acquisition systems HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF that are located at the bacterial outer membrane or the periplasm. Our computational studies provided plausible 3D models for HbpA, SapA, PE, and HxuA interactions with heme. Generation and characterization of single mutants in the hxuCBA, hpe, sapA, and hbpA genes provided evidence for participation in heme binding-storage and inter-bacterial donation. The hxuA, sapA, hbpA, and hpe genes showed differential expression and responded to heme. Moreover, HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF presented moonlighting properties related to resistance to antimicrobial peptides or glutathione import, together likely contributing to the NTHi-host airway interplay, as observed upon cultured airway epithelia and in vivo lung infection. The observed multi-functionality was shown to be system-specific, thus limiting redundancy. Together, we provide evidence for heme uptake systems as bacterial factors that act in a coordinated and multi-functional manner to subvert nutritional- and other sources of host innate immunity during NTHi airway infection.",

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author = "Irene Rodriguez-Arce and Tamim Al-Jubair and Begona Euba and Ariadna Fernandez-Calvet and Celia Gil-Campillo and Sara Marti and Susanna Tornroth-Horsefield and Kristian Riesbeck and Junkal Garmendia",

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T1 - Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

AU - Rodriguez-Arce, Irene

AU - Al-Jubair, Tamim

AU - Euba, Begona

AU - Fernandez-Calvet, Ariadna

AU - Gil-Campillo, Celia

AU - Marti, Sara

AU - Tornroth-Horsefield, Susanna

AU - Riesbeck, Kristian

AU - Garmendia, Junkal

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N2 - Nutrient iron sequestration is the most significant form of nutritional immunity and causes bacterial pathogens to evolve strategies of host iron scavenging. Cigarette smoking contains iron particulates altering lung and systemic iron homeostasis, which may enhance colonization in the lungs of patients suffering chronic obstructive pulmonary disease (COPD) by opportunistic pathogens such as nontypeable. NTHi is a heme auxotroph, and the NTHi genome contains multiple heme acquisition systems whose role in pulmonary infection requires a global understanding. In this study, we determined the relative contribution to NTHi airway infection of the four heme-acquisition systems HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF that are located at the bacterial outer membrane or the periplasm. Our computational studies provided plausible 3D models for HbpA, SapA, PE, and HxuA interactions with heme. Generation and characterization of single mutants in the hxuCBA, hpe, sapA, and hbpA genes provided evidence for participation in heme binding-storage and inter-bacterial donation. The hxuA, sapA, hbpA, and hpe genes showed differential expression and responded to heme. Moreover, HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF presented moonlighting properties related to resistance to antimicrobial peptides or glutathione import, together likely contributing to the NTHi-host airway interplay, as observed upon cultured airway epithelia and in vivo lung infection. The observed multi-functionality was shown to be system-specific, thus limiting redundancy. Together, we provide evidence for heme uptake systems as bacterial factors that act in a coordinated and multi-functional manner to subvert nutritional- and other sources of host innate immunity during NTHi airway infection.

AB - Nutrient iron sequestration is the most significant form of nutritional immunity and causes bacterial pathogens to evolve strategies of host iron scavenging. Cigarette smoking contains iron particulates altering lung and systemic iron homeostasis, which may enhance colonization in the lungs of patients suffering chronic obstructive pulmonary disease (COPD) by opportunistic pathogens such as nontypeable. NTHi is a heme auxotroph, and the NTHi genome contains multiple heme acquisition systems whose role in pulmonary infection requires a global understanding. In this study, we determined the relative contribution to NTHi airway infection of the four heme-acquisition systems HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF that are located at the bacterial outer membrane or the periplasm. Our computational studies provided plausible 3D models for HbpA, SapA, PE, and HxuA interactions with heme. Generation and characterization of single mutants in the hxuCBA, hpe, sapA, and hbpA genes provided evidence for participation in heme binding-storage and inter-bacterial donation. The hxuA, sapA, hbpA, and hpe genes showed differential expression and responded to heme. Moreover, HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF presented moonlighting properties related to resistance to antimicrobial peptides or glutathione import, together likely contributing to the NTHi-host airway interplay, as observed upon cultured airway epithelia and in vivo lung infection. The observed multi-functionality was shown to be system-specific, thus limiting redundancy. Together, we provide evidence for heme uptake systems as bacterial factors that act in a coordinated and multi-functional manner to subvert nutritional- and other sources of host innate immunity during NTHi airway infection.

KW - Haemophilus influenzae

KW - heme binding

KW - iron nutritional immunity

KW - protein moonlighting

KW - respiratory infection

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DO - 10.1080/21505594.2019.1596506

M3 - Journal article

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SN - 2150-5594

VL - 10

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JO - Virulence

JF - Virulence

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