Microfluidic analysis of salt-stress-mediated antibiotic tolerance in Mycobacterium smegmatis.

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Title: Microfluidic analysis of salt-stress-mediated antibiotic tolerance in Mycobacterium smegmatis.
Authors: Agrawal, Akanksha1 (AUTHOR), Udaya Kumar, Dhananjay1 (AUTHOR), Mukherjee, Raju1 (AUTHOR) raju.mukherjee@iisertirupati.ac.in, Mampallil, Dileep2 (AUTHOR) dileep.mampallil@iisertirupati.ac.in
Source: Lab on a Chip. 12/21/2025, Vol. 25 Issue 24, p6718-6729. 12p.
Subjects: Mycobacterium smegmatis, Drug resistance, Microfluidics, Bacterial growth, Salinization, Gene expression, Multidrug tolerance (Microbiology), Membrane transport proteins
Abstract: Understanding how bacteria respond to complex environmental stresses is essential for addressing antibiotic resistance. In the natural environment, bacteria can experience salt stress, for instance, due to spontaneous water evaporation. Here, we present a microfluidic platform that enables long-term culture of Mycobacterium smegmatis, a fast-growing, non-pathogenic model for mycobacteria. Using a microfluidic gradient generator, we established stable salt and antibiotic concentration profiles across growth chambers and monitored bacterial proliferation over multiple generations. When exposed to antibiotics in conjunction with elevated salt concentrations, M. smegmatis exhibited a significant increase in the minimum inhibitory concentration, indicating a salt-induced drug resistance. Salt stress also led to slower growth, shorter cell length, and reduced division asymmetry. While efflux pump inhibitors partially restored antibiotic sensitivity, gene expression profiles and dye-based efflux assays showed minimal early activation of known efflux genes, but upregulation of ribosomal biosynthesis and stress adaptation. In general, these findings demonstrate how abiotic stress promotes phenotypic drug tolerance and reshapes antibiotic susceptibility prior to developing genetic resistance, thus providing valuable insights into managing the global threat of antibiotic resistance. [ABSTRACT FROM AUTHOR]
Copyright of Lab on a Chip is the property of Royal Society of Chemistry and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 189732279
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  Data: Microfluidic analysis of salt-stress-mediated antibiotic tolerance in Mycobacterium smegmatis.
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  Data: <searchLink fieldCode="AR" term="%22Agrawal%2C+Akanksha%22">Agrawal, Akanksha</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Udaya+Kumar%2C+Dhananjay%22">Udaya Kumar, Dhananjay</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mukherjee%2C+Raju%22">Mukherjee, Raju</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> raju.mukherjee@iisertirupati.ac.in</i><br /><searchLink fieldCode="AR" term="%22Mampallil%2C+Dileep%22">Mampallil, Dileep</searchLink><relatesTo>2</relatesTo> (AUTHOR)<i> dileep.mampallil@iisertirupati.ac.in</i>
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  Data: <searchLink fieldCode="JN" term="%22Lab+on+a+Chip%22">Lab on a Chip</searchLink>. 12/21/2025, Vol. 25 Issue 24, p6718-6729. 12p.
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  Data: <searchLink fieldCode="DE" term="%22Mycobacterium+smegmatis%22">Mycobacterium smegmatis</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance%22">Drug resistance</searchLink><br /><searchLink fieldCode="DE" term="%22Microfluidics%22">Microfluidics</searchLink><br /><searchLink fieldCode="DE" term="%22Bacterial+growth%22">Bacterial growth</searchLink><br /><searchLink fieldCode="DE" term="%22Salinization%22">Salinization</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22Multidrug+tolerance+%28Microbiology%29%22">Multidrug tolerance (Microbiology)</searchLink><br /><searchLink fieldCode="DE" term="%22Membrane+transport+proteins%22">Membrane transport proteins</searchLink>
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  Data: Understanding how bacteria respond to complex environmental stresses is essential for addressing antibiotic resistance. In the natural environment, bacteria can experience salt stress, for instance, due to spontaneous water evaporation. Here, we present a microfluidic platform that enables long-term culture of Mycobacterium smegmatis, a fast-growing, non-pathogenic model for mycobacteria. Using a microfluidic gradient generator, we established stable salt and antibiotic concentration profiles across growth chambers and monitored bacterial proliferation over multiple generations. When exposed to antibiotics in conjunction with elevated salt concentrations, M. smegmatis exhibited a significant increase in the minimum inhibitory concentration, indicating a salt-induced drug resistance. Salt stress also led to slower growth, shorter cell length, and reduced division asymmetry. While efflux pump inhibitors partially restored antibiotic sensitivity, gene expression profiles and dye-based efflux assays showed minimal early activation of known efflux genes, but upregulation of ribosomal biosynthesis and stress adaptation. In general, these findings demonstrate how abiotic stress promotes phenotypic drug tolerance and reshapes antibiotic susceptibility prior to developing genetic resistance, thus providing valuable insights into managing the global threat of antibiotic resistance. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Lab on a Chip is the property of Royal Society of Chemistry and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1039/d5lc00713e
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      – Code: eng
        Text: English
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        PageCount: 12
        StartPage: 6718
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      – SubjectFull: Mycobacterium smegmatis
        Type: general
      – SubjectFull: Drug resistance
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      – SubjectFull: Microfluidics
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      – SubjectFull: Bacterial growth
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      – SubjectFull: Salinization
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      – SubjectFull: Gene expression
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      – SubjectFull: Multidrug tolerance (Microbiology)
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      – SubjectFull: Membrane transport proteins
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      – TitleFull: Microfluidic analysis of salt-stress-mediated antibiotic tolerance in Mycobacterium smegmatis.
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            NameFull: Agrawal, Akanksha
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              Text: 12/21/2025
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              Y: 2025
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