A link between pH homeostasis and colistin resistance in bacteria

Abstract Colistin resistance is complex and multifactorial. DbcA is an inner membrane protein belonging to the DedA superfamily required for maintaining extreme colistin resistance of Burkholderia thailandensis. The molecular mechanisms behind this remain unclear. Here, we report that ∆dbcA displays...

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Autores principales:	Pradip R. Panta, William T. Doerrler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb6eba5f34604ed08c0841776b10f802
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spelling	oai:doaj.org-article:cb6eba5f34604ed08c0841776b10f8022021-12-02T17:45:17ZA link between pH homeostasis and colistin resistance in bacteria10.1038/s41598-021-92718-72045-2322https://doaj.org/article/cb6eba5f34604ed08c0841776b10f8022021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92718-7https://doaj.org/toc/2045-2322Abstract Colistin resistance is complex and multifactorial. DbcA is an inner membrane protein belonging to the DedA superfamily required for maintaining extreme colistin resistance of Burkholderia thailandensis. The molecular mechanisms behind this remain unclear. Here, we report that ∆dbcA displays alkaline pH/bicarbonate sensitivity and propose a role of DbcA in extreme colistin resistance of B. thailandensis by maintaining cytoplasmic pH homeostasis. We found that alkaline pH or presence of sodium bicarbonate displays a synergistic effect with colistin against not only extremely colistin resistant species like B. thailandensis and Serratia marcescens, but also a majority of Gram-negative and Gram-positive bacteria tested, suggesting a link between cytoplasmic pH homeostasis and colistin resistance across species. We found that lowering the level of oxygen in the growth media or supplementation of fermentable sugars such as glucose not only alleviated alkaline pH stress, but also increased colistin resistance in most bacteria tested, likely by avoiding cytoplasmic alkalinization. Our observations suggest a previously unreported link between pH, oxygen, and colistin resistance. We propose that maintaining optimal cytoplasmic pH is required for colistin resistance in a majority of bacterial species, consistent with the emerging link between cytoplasmic pH homeostasis and antibiotic resistance.Pradip R. PantaWilliam T. DoerrlerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pradip R. Panta William T. Doerrler A link between pH homeostasis and colistin resistance in bacteria
description	Abstract Colistin resistance is complex and multifactorial. DbcA is an inner membrane protein belonging to the DedA superfamily required for maintaining extreme colistin resistance of Burkholderia thailandensis. The molecular mechanisms behind this remain unclear. Here, we report that ∆dbcA displays alkaline pH/bicarbonate sensitivity and propose a role of DbcA in extreme colistin resistance of B. thailandensis by maintaining cytoplasmic pH homeostasis. We found that alkaline pH or presence of sodium bicarbonate displays a synergistic effect with colistin against not only extremely colistin resistant species like B. thailandensis and Serratia marcescens, but also a majority of Gram-negative and Gram-positive bacteria tested, suggesting a link between cytoplasmic pH homeostasis and colistin resistance across species. We found that lowering the level of oxygen in the growth media or supplementation of fermentable sugars such as glucose not only alleviated alkaline pH stress, but also increased colistin resistance in most bacteria tested, likely by avoiding cytoplasmic alkalinization. Our observations suggest a previously unreported link between pH, oxygen, and colistin resistance. We propose that maintaining optimal cytoplasmic pH is required for colistin resistance in a majority of bacterial species, consistent with the emerging link between cytoplasmic pH homeostasis and antibiotic resistance.
format	article
author	Pradip R. Panta William T. Doerrler
author_facet	Pradip R. Panta William T. Doerrler
author_sort	Pradip R. Panta
title	A link between pH homeostasis and colistin resistance in bacteria
title_short	A link between pH homeostasis and colistin resistance in bacteria
title_full	A link between pH homeostasis and colistin resistance in bacteria
title_fullStr	A link between pH homeostasis and colistin resistance in bacteria
title_full_unstemmed	A link between pH homeostasis and colistin resistance in bacteria
title_sort	link between ph homeostasis and colistin resistance in bacteria
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cb6eba5f34604ed08c0841776b10f802
work_keys_str_mv	AT pradiprpanta alinkbetweenphhomeostasisandcolistinresistanceinbacteria AT williamtdoerrler alinkbetweenphhomeostasisandcolistinresistanceinbacteria AT pradiprpanta linkbetweenphhomeostasisandcolistinresistanceinbacteria AT williamtdoerrler linkbetweenphhomeostasisandcolistinresistanceinbacteria
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A link between pH homeostasis and colistin resistance in bacteria

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