Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae

Research output: Contribution to journalJournal articleResearchpeer-review

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Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae. / Jalalvand, Farshid; Su, Yu-Ching; Manat, Guillaume; Chernobrovkin, Alexey; Kadari, Mahendar; Jonsson, Sandra; Janousková, Martina; Rutishauser, Dorothea; Semsey, Szabolcs; Løbner-Olesen, Anders; Sandblad, Linda; Flärdh, Klas; Mengin-Lecreulx, Dominique; Zubarev, Roman A.; Riesbeck, Kristian.

In: Frontiers in Cellular and Infection Microbiology, Vol. 12, 984955, 2022.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jalalvand, F, Su, Y-C, Manat, G, Chernobrovkin, A, Kadari, M, Jonsson, S, Janousková, M, Rutishauser, D, Semsey, S, Løbner-Olesen, A, Sandblad, L, Flärdh, K, Mengin-Lecreulx, D, Zubarev, RA & Riesbeck, K 2022, 'Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae', Frontiers in Cellular and Infection Microbiology, vol. 12, 984955. https://doi.org/10.3389/fcimb.2022.984955

APA

Jalalvand, F., Su, Y-C., Manat, G., Chernobrovkin, A., Kadari, M., Jonsson, S., Janousková, M., Rutishauser, D., Semsey, S., Løbner-Olesen, A., Sandblad, L., Flärdh, K., Mengin-Lecreulx, D., Zubarev, R. A., & Riesbeck, K. (2022). Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae. Frontiers in Cellular and Infection Microbiology, 12, [984955]. https://doi.org/10.3389/fcimb.2022.984955

Vancouver

Jalalvand F, Su Y-C, Manat G, Chernobrovkin A, Kadari M, Jonsson S et al. Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae. Frontiers in Cellular and Infection Microbiology. 2022;12. 984955. https://doi.org/10.3389/fcimb.2022.984955

Author

Jalalvand, Farshid ; Su, Yu-Ching ; Manat, Guillaume ; Chernobrovkin, Alexey ; Kadari, Mahendar ; Jonsson, Sandra ; Janousková, Martina ; Rutishauser, Dorothea ; Semsey, Szabolcs ; Løbner-Olesen, Anders ; Sandblad, Linda ; Flärdh, Klas ; Mengin-Lecreulx, Dominique ; Zubarev, Roman A. ; Riesbeck, Kristian. / Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae. In: Frontiers in Cellular and Infection Microbiology. 2022 ; Vol. 12.

Bibtex

@article{63b31ba58d2b41e585b756beeca01b24,
title = "Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae",
abstract = "The human pathogen Haemophilus influenzae causes respiratory tract infections and is commonly associated with prolonged carriage in patients with chronic obstructive pulmonary disease. Production of outer membrane vesicles (OMVs) is a ubiquitous phenomenon observed in Gram-negative bacteria including H. influenzae. OMVs play an important role in various interactions with the human host; from neutralization of antibodies and complement activation to spread of antimicrobial resistance. Upon vesiculation certain proteins are found in OMVs and some proteins are retained at the cell membrane. The mechanism for this phenomenon is not fully elucidated. We employed mass spectrometry to study vesiculation and the fate of proteins in the outer membrane. Functional groups of proteins were differentially distributed on the cell surface and in OMVs. Despite its supposedly periplasmic and outer membrane location, we found that the peptidoglycan synthase-activator Lipoprotein A (LpoA) was accumulated in OMVs relative to membrane fractions. A mutant devoid of LpoA lost its fitness as revealed by growth and electron microscopy. Furthermore, high-pressure liquid chromatography disclosed a lower concentration (55%) of peptidoglycan in the LpoA-deficient H. influenzae compared to the parent wild type bacterium. Using an LpoA-mNeonGreen fusion protein and fluorescence microscopy, we observed that LpoA was enriched in {"}foci{"} in the cell envelope, and further located in the septum during cell division. To define the fate of LpoA, C-terminally truncated LpoA-variants were constructed, and we found that the LpoA C-terminal domain promoted optimal transportation to the OMVs as revealed by flow cytometry. Taken together, our study highlights the importance of LpoA for H. influenzae peptidoglycan biogenesis and provides novel insights into cell wall integrity and OMV production.",
keywords = "Humans, Haemophilus influenzae/metabolism, Protein Domains, Bacterial Outer Membrane Proteins/metabolism, Lipoprotein(a)/metabolism, Peptidoglycan/metabolism, Cell Wall/metabolism, Anti-Infective Agents/metabolism",
author = "Farshid Jalalvand and Yu-Ching Su and Guillaume Manat and Alexey Chernobrovkin and Mahendar Kadari and Sandra Jonsson and Martina Janouskov{\'a} and Dorothea Rutishauser and Szabolcs Semsey and Anders L{\o}bner-Olesen and Linda Sandblad and Klas Fl{\"a}rdh and Dominique Mengin-Lecreulx and Zubarev, {Roman A.} and Kristian Riesbeck",
note = "Copyright {\textcopyright} 2022 Jalalvand, Su, Manat, Chernobrovkin, Kadari, Jonsson, Janouskov{\'a}, Rutishauser, Semsey, L{\o}bner-Olesen, Sandblad, Fl{\"a}rdh, Mengin-Lecreulx, Zubarev and Riesbeck.",
year = "2022",
doi = "10.3389/fcimb.2022.984955",
language = "English",
volume = "12",
journal = "Frontiers in Cellular and Infection Microbiology",
issn = "2235-2988",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Protein domain-dependent vesiculation of Lipoprotein A, a protein that is important in cell wall synthesis and fitness of the human respiratory pathogen Haemophilus influenzae

AU - Jalalvand, Farshid

AU - Su, Yu-Ching

AU - Manat, Guillaume

AU - Chernobrovkin, Alexey

AU - Kadari, Mahendar

AU - Jonsson, Sandra

AU - Janousková, Martina

AU - Rutishauser, Dorothea

AU - Semsey, Szabolcs

AU - Løbner-Olesen, Anders

AU - Sandblad, Linda

AU - Flärdh, Klas

AU - Mengin-Lecreulx, Dominique

AU - Zubarev, Roman A.

AU - Riesbeck, Kristian

N1 - Copyright © 2022 Jalalvand, Su, Manat, Chernobrovkin, Kadari, Jonsson, Janousková, Rutishauser, Semsey, Løbner-Olesen, Sandblad, Flärdh, Mengin-Lecreulx, Zubarev and Riesbeck.

PY - 2022

Y1 - 2022

N2 - The human pathogen Haemophilus influenzae causes respiratory tract infections and is commonly associated with prolonged carriage in patients with chronic obstructive pulmonary disease. Production of outer membrane vesicles (OMVs) is a ubiquitous phenomenon observed in Gram-negative bacteria including H. influenzae. OMVs play an important role in various interactions with the human host; from neutralization of antibodies and complement activation to spread of antimicrobial resistance. Upon vesiculation certain proteins are found in OMVs and some proteins are retained at the cell membrane. The mechanism for this phenomenon is not fully elucidated. We employed mass spectrometry to study vesiculation and the fate of proteins in the outer membrane. Functional groups of proteins were differentially distributed on the cell surface and in OMVs. Despite its supposedly periplasmic and outer membrane location, we found that the peptidoglycan synthase-activator Lipoprotein A (LpoA) was accumulated in OMVs relative to membrane fractions. A mutant devoid of LpoA lost its fitness as revealed by growth and electron microscopy. Furthermore, high-pressure liquid chromatography disclosed a lower concentration (55%) of peptidoglycan in the LpoA-deficient H. influenzae compared to the parent wild type bacterium. Using an LpoA-mNeonGreen fusion protein and fluorescence microscopy, we observed that LpoA was enriched in "foci" in the cell envelope, and further located in the septum during cell division. To define the fate of LpoA, C-terminally truncated LpoA-variants were constructed, and we found that the LpoA C-terminal domain promoted optimal transportation to the OMVs as revealed by flow cytometry. Taken together, our study highlights the importance of LpoA for H. influenzae peptidoglycan biogenesis and provides novel insights into cell wall integrity and OMV production.

AB - The human pathogen Haemophilus influenzae causes respiratory tract infections and is commonly associated with prolonged carriage in patients with chronic obstructive pulmonary disease. Production of outer membrane vesicles (OMVs) is a ubiquitous phenomenon observed in Gram-negative bacteria including H. influenzae. OMVs play an important role in various interactions with the human host; from neutralization of antibodies and complement activation to spread of antimicrobial resistance. Upon vesiculation certain proteins are found in OMVs and some proteins are retained at the cell membrane. The mechanism for this phenomenon is not fully elucidated. We employed mass spectrometry to study vesiculation and the fate of proteins in the outer membrane. Functional groups of proteins were differentially distributed on the cell surface and in OMVs. Despite its supposedly periplasmic and outer membrane location, we found that the peptidoglycan synthase-activator Lipoprotein A (LpoA) was accumulated in OMVs relative to membrane fractions. A mutant devoid of LpoA lost its fitness as revealed by growth and electron microscopy. Furthermore, high-pressure liquid chromatography disclosed a lower concentration (55%) of peptidoglycan in the LpoA-deficient H. influenzae compared to the parent wild type bacterium. Using an LpoA-mNeonGreen fusion protein and fluorescence microscopy, we observed that LpoA was enriched in "foci" in the cell envelope, and further located in the septum during cell division. To define the fate of LpoA, C-terminally truncated LpoA-variants were constructed, and we found that the LpoA C-terminal domain promoted optimal transportation to the OMVs as revealed by flow cytometry. Taken together, our study highlights the importance of LpoA for H. influenzae peptidoglycan biogenesis and provides novel insights into cell wall integrity and OMV production.

KW - Humans

KW - Haemophilus influenzae/metabolism

KW - Protein Domains

KW - Bacterial Outer Membrane Proteins/metabolism

KW - Lipoprotein(a)/metabolism

KW - Peptidoglycan/metabolism

KW - Cell Wall/metabolism

KW - Anti-Infective Agents/metabolism

U2 - 10.3389/fcimb.2022.984955

DO - 10.3389/fcimb.2022.984955

M3 - Journal article

C2 - 36275016

VL - 12

JO - Frontiers in Cellular and Infection Microbiology

JF - Frontiers in Cellular and Infection Microbiology

SN - 2235-2988

M1 - 984955

ER -

ID: 323547982