BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function

ABSTRACT Acinetobacter baumannii is a high-risk pathogen due to the rapid global spread of multidrug-resistant lineages. Its phylogenetic divergence from other ESKAPE pathogens means that determinants of its antimicrobial resistance can be difficult to extrapolate from other widely studied bacteria....

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Autores principales:	Rhys Grinter, Faye C. Morris, Rhys A. Dunstan, Pok Man Leung, Ashleigh Kropp, Matthew Belousoff, Sachith D. Gunasinghe, Nichollas E. Scott, Simone Beckham, Anton Y. Peleg, Chris Greening, Jian Li, Eva Heinz, Trevor Lithgow
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Acinetobacter baumannii cell division cell envelope outer membrane proteins Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c28d5a874e247828497d0aa8a7f21e3
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spelling	oai:doaj.org-article:1c28d5a874e247828497d0aa8a7f21e32021-11-10T18:37:51ZBonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function10.1128/mBio.01480-212150-7511https://doaj.org/article/1c28d5a874e247828497d0aa8a7f21e32021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01480-21https://doaj.org/toc/2150-7511ABSTRACT Acinetobacter baumannii is a high-risk pathogen due to the rapid global spread of multidrug-resistant lineages. Its phylogenetic divergence from other ESKAPE pathogens means that determinants of its antimicrobial resistance can be difficult to extrapolate from other widely studied bacteria. A recent study showed that A. baumannii upregulates production of an outer membrane lipoprotein, which we designate BonA, in response to challenge with polymyxins. Here, we show that BonA has limited sequence similarity and distinct structural features compared to lipoproteins from other bacterial species. Analyses through X-ray crystallography, small-angle X-ray scattering, electron microscopy, and multiangle light scattering demonstrate that BonA has a dual BON (Bacterial OsmY and Nodulation) domain architecture and forms a decamer via an unusual oligomerization mechanism. This analysis also indicates this decamer is transient, suggesting dynamic oligomerization plays a role in BonA function. Antisera recognizing BonA shows it is an outer membrane protein localized to the divisome. Loss of BonA modulates the density of the outer membrane, consistent with a change in its structure or link to the peptidoglycan, and prevents motility in a clinical strain (ATCC 17978). Consistent with these findings, the dimensions of the BonA decamer are sufficient to permeate the peptidoglycan layer, with the potential to form a membrane-spanning complex during cell division. IMPORTANCE The pathogen Acinetobacter baumannii is considered an urgent threat to human health. A. baumannii is highly resistant to treatment with antibiotics, in part due to its protective cell envelope. This bacterium is only distantly related to other bacterial pathogens, so its cell envelope has distinct properties and contains components distinct from those of other bacteria that support its function. Here, we report the discovery of BonA, a protein that supports A. baumannii outer envelope function and is required for cell motility. We determine the atomic structure of BonA and show that it forms part of the cell division machinery and functions by forming a complex, features that mirror those of distantly related homologs from other bacteria. By improving our understanding of the A. baumannii cell envelope this work will assist in treating this pathogen.Rhys GrinterFaye C. MorrisRhys A. DunstanPok Man LeungAshleigh KroppMatthew BelousoffSachith D. GunasingheNichollas E. ScottSimone BeckhamAnton Y. PelegChris GreeningJian LiEva HeinzTrevor LithgowAmerican Society for MicrobiologyarticleAcinetobacter baumanniicell divisioncell envelopeouter membrane proteinsMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acinetobacter baumannii cell division cell envelope outer membrane proteins Microbiology QR1-502
spellingShingle	Acinetobacter baumannii cell division cell envelope outer membrane proteins Microbiology QR1-502 Rhys Grinter Faye C. Morris Rhys A. Dunstan Pok Man Leung Ashleigh Kropp Matthew Belousoff Sachith D. Gunasinghe Nichollas E. Scott Simone Beckham Anton Y. Peleg Chris Greening Jian Li Eva Heinz Trevor Lithgow BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function
description	ABSTRACT Acinetobacter baumannii is a high-risk pathogen due to the rapid global spread of multidrug-resistant lineages. Its phylogenetic divergence from other ESKAPE pathogens means that determinants of its antimicrobial resistance can be difficult to extrapolate from other widely studied bacteria. A recent study showed that A. baumannii upregulates production of an outer membrane lipoprotein, which we designate BonA, in response to challenge with polymyxins. Here, we show that BonA has limited sequence similarity and distinct structural features compared to lipoproteins from other bacterial species. Analyses through X-ray crystallography, small-angle X-ray scattering, electron microscopy, and multiangle light scattering demonstrate that BonA has a dual BON (Bacterial OsmY and Nodulation) domain architecture and forms a decamer via an unusual oligomerization mechanism. This analysis also indicates this decamer is transient, suggesting dynamic oligomerization plays a role in BonA function. Antisera recognizing BonA shows it is an outer membrane protein localized to the divisome. Loss of BonA modulates the density of the outer membrane, consistent with a change in its structure or link to the peptidoglycan, and prevents motility in a clinical strain (ATCC 17978). Consistent with these findings, the dimensions of the BonA decamer are sufficient to permeate the peptidoglycan layer, with the potential to form a membrane-spanning complex during cell division. IMPORTANCE The pathogen Acinetobacter baumannii is considered an urgent threat to human health. A. baumannii is highly resistant to treatment with antibiotics, in part due to its protective cell envelope. This bacterium is only distantly related to other bacterial pathogens, so its cell envelope has distinct properties and contains components distinct from those of other bacteria that support its function. Here, we report the discovery of BonA, a protein that supports A. baumannii outer envelope function and is required for cell motility. We determine the atomic structure of BonA and show that it forms part of the cell division machinery and functions by forming a complex, features that mirror those of distantly related homologs from other bacteria. By improving our understanding of the A. baumannii cell envelope this work will assist in treating this pathogen.
format	article
author	Rhys Grinter Faye C. Morris Rhys A. Dunstan Pok Man Leung Ashleigh Kropp Matthew Belousoff Sachith D. Gunasinghe Nichollas E. Scott Simone Beckham Anton Y. Peleg Chris Greening Jian Li Eva Heinz Trevor Lithgow
author_facet	Rhys Grinter Faye C. Morris Rhys A. Dunstan Pok Man Leung Ashleigh Kropp Matthew Belousoff Sachith D. Gunasinghe Nichollas E. Scott Simone Beckham Anton Y. Peleg Chris Greening Jian Li Eva Heinz Trevor Lithgow
author_sort	Rhys Grinter
title	BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function
title_short	BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function
title_full	BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function
title_fullStr	BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function
title_full_unstemmed	BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function
title_sort	bona from <italic toggle="yes">acinetobacter baumannii</italic> forms a divisome-localized decamer that supports outer envelope function
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/1c28d5a874e247828497d0aa8a7f21e3
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BonA from <italic toggle="yes">Acinetobacter baumannii</italic> Forms a Divisome-Localized Decamer That Supports Outer Envelope Function

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