Roles of Lon protease and its substrate MarA during sodium salicylate-mediated growth reduction and antibiotic resistance in Escherichia coli

Chetana Bhaskarla, Mrinmoy Das, Taru Verma, Anujith Kumar, S. Mahadevan, Dipankar Nandi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The cellular proteolytic machinery orchestrates protein turnover and regulates several key biological processes. This study addresses the roles of Lon, a major ATP-dependent protease, in modulating the responses of Escherichia coli strain MG1655 to low and high amounts of sodium salicyclate (NaSal), a widely used clinically relevant analgesic. NaSal affects several bacterial responses, including growth and resistance to multiple antibiotics. The loss of lon reduces growth in response to high, but not low, amounts of NaSal. From amongst a panel of Lon substrates, MarA was identified to be the downstream target of Lon. Thus, stabilization of MarA in the absence of lon lowers growth of the strain in the presence of higher amounts of NaSal. The steady-state transcript levels of marA and its target genes, acrA, acrB and tolC, are higher in the Dlon strain compared with the WT strain. Consequently, the resistance to antibiotics, e.g. tetracycline and nalidixic acid, is enhanced in Δlon in a marA-dependent manner. Furthermore, the target genes of MarA, i.e. acrB and tolC, are responsible for NaSal-mediated antibiotic resistance. Studies using atomic force microscopy demonstrated that ciprofloxacin led to greater cell filamentation, which is lower in the Dlon strain due to higher levels of MarA. Overall, this study delineates the roles of Lon protease, its substrate MarA and downstream targets of MarA, e.g. acrB and tolC, during NaSal-mediated growth reduction and antibiotic resistance. The implications of these observations in the adaptation of E. coli under different environmental conditions are discussed.

Original languageEnglish
Article number000271
Pages (from-to)764-776
Number of pages13
JournalMicrobiology (United Kingdom)
Volume162
Issue number5
DOIs
Publication statusPublished - 01-05-2016

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Protease La
Sodium Salicylate
Microbial Drug Resistance
Nose
Escherichia coli
Growth
ATP-Dependent Proteases
Biological Phenomena
Nalidixic Acid
Atomic Force Microscopy
Ciprofloxacin
Tetracycline
Genes
Analgesics
Sodium
Anti-Bacterial Agents

All Science Journal Classification (ASJC) codes

  • Microbiology

Cite this

Bhaskarla, Chetana ; Das, Mrinmoy ; Verma, Taru ; Kumar, Anujith ; Mahadevan, S. ; Nandi, Dipankar. / Roles of Lon protease and its substrate MarA during sodium salicylate-mediated growth reduction and antibiotic resistance in Escherichia coli. In: Microbiology (United Kingdom). 2016 ; Vol. 162, No. 5. pp. 764-776.
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Roles of Lon protease and its substrate MarA during sodium salicylate-mediated growth reduction and antibiotic resistance in Escherichia coli. / Bhaskarla, Chetana; Das, Mrinmoy; Verma, Taru; Kumar, Anujith; Mahadevan, S.; Nandi, Dipankar.

In: Microbiology (United Kingdom), Vol. 162, No. 5, 000271, 01.05.2016, p. 764-776.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Roles of Lon protease and its substrate MarA during sodium salicylate-mediated growth reduction and antibiotic resistance in Escherichia coli

AU - Bhaskarla, Chetana

AU - Das, Mrinmoy

AU - Verma, Taru

AU - Kumar, Anujith

AU - Mahadevan, S.

AU - Nandi, Dipankar

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N2 - The cellular proteolytic machinery orchestrates protein turnover and regulates several key biological processes. This study addresses the roles of Lon, a major ATP-dependent protease, in modulating the responses of Escherichia coli strain MG1655 to low and high amounts of sodium salicyclate (NaSal), a widely used clinically relevant analgesic. NaSal affects several bacterial responses, including growth and resistance to multiple antibiotics. The loss of lon reduces growth in response to high, but not low, amounts of NaSal. From amongst a panel of Lon substrates, MarA was identified to be the downstream target of Lon. Thus, stabilization of MarA in the absence of lon lowers growth of the strain in the presence of higher amounts of NaSal. The steady-state transcript levels of marA and its target genes, acrA, acrB and tolC, are higher in the Dlon strain compared with the WT strain. Consequently, the resistance to antibiotics, e.g. tetracycline and nalidixic acid, is enhanced in Δlon in a marA-dependent manner. Furthermore, the target genes of MarA, i.e. acrB and tolC, are responsible for NaSal-mediated antibiotic resistance. Studies using atomic force microscopy demonstrated that ciprofloxacin led to greater cell filamentation, which is lower in the Dlon strain due to higher levels of MarA. Overall, this study delineates the roles of Lon protease, its substrate MarA and downstream targets of MarA, e.g. acrB and tolC, during NaSal-mediated growth reduction and antibiotic resistance. The implications of these observations in the adaptation of E. coli under different environmental conditions are discussed.

AB - The cellular proteolytic machinery orchestrates protein turnover and regulates several key biological processes. This study addresses the roles of Lon, a major ATP-dependent protease, in modulating the responses of Escherichia coli strain MG1655 to low and high amounts of sodium salicyclate (NaSal), a widely used clinically relevant analgesic. NaSal affects several bacterial responses, including growth and resistance to multiple antibiotics. The loss of lon reduces growth in response to high, but not low, amounts of NaSal. From amongst a panel of Lon substrates, MarA was identified to be the downstream target of Lon. Thus, stabilization of MarA in the absence of lon lowers growth of the strain in the presence of higher amounts of NaSal. The steady-state transcript levels of marA and its target genes, acrA, acrB and tolC, are higher in the Dlon strain compared with the WT strain. Consequently, the resistance to antibiotics, e.g. tetracycline and nalidixic acid, is enhanced in Δlon in a marA-dependent manner. Furthermore, the target genes of MarA, i.e. acrB and tolC, are responsible for NaSal-mediated antibiotic resistance. Studies using atomic force microscopy demonstrated that ciprofloxacin led to greater cell filamentation, which is lower in the Dlon strain due to higher levels of MarA. Overall, this study delineates the roles of Lon protease, its substrate MarA and downstream targets of MarA, e.g. acrB and tolC, during NaSal-mediated growth reduction and antibiotic resistance. The implications of these observations in the adaptation of E. coli under different environmental conditions are discussed.

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