An E. coli lon mutant conferring partial resistance to colicin may reveal a novel role in regulating proteins involved in the translocation of colicin

Lee, Yuan-Yu; Hu, Hsiao-Tin; Liang, Po‐Huang; Chak, Kin‐Fu

doi:10.1016/j.bbrc.2006.05.062

Cited by 3 publications

(2 citation statements)

References 31 publications

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“…We found that lon mutation caused a multidrug resistance phenotype with increased MICs of several antibiotics. In addition to the results presented here, lon mutation in E. coli has also been shown to cause low resistance to colicin (Lee et al ., ), doxycycline (Girgis et al ., ), the plant oils thymol and menthol (Shapira and Mimran, ) and to be positively selected following growth at sub‐inhibitory concentrations of cefoxitin (Girgis et al ., ). Taken together, these results show that a lon mutation causes a lower multidrug resistance than that resulting from typical acrAB ‐inducing mutations such as marR or acrR mutations.…”

Section: Discussionmentioning

confidence: 99%

Lon protease inactivation, or translocation of the lon gene, potentiate bacterial evolution to antibiotic resistance

Nicoloff

Andersson

2013

Molecular Microbiology

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SummaryPrevious work demonstrated that selection for Escherichia coli mutants with low antibiotic resistance frequently resulted in co-selection of lon mutations and that lon − mutants evolved higher-level resistance faster than a lon + strain. Here we show that lon mutation causes a very low multidrug resistance by inducing the AcrAB-TolC pump via stabilization of the acrAB transcriptional activators MarA and SoxS, which are substrates of the Lon protease. Fast evolution of lon − mutants towards higher resistance involves selection of frequent next-step mutations consisting of large duplications including acrAB and the mutated lon gene. Resistance results from the combined effects of acrAB duplication and lon mutation increasing dosage of efflux pump. In contrast, when acrAB duplication occurs as the first step mutation, increased Lon activity caused by lon + co-duplication mitigates the effect of acrAB duplication on resistance, and faster evolution towards higher resistance is not observed. As predicted, when the functional lon gene is relocated far from acrAB to prevent their co-duplication, first-step acrAB duplication confers higher resistance, which then allows selection of frequent next-step mutations and results in faster evolution towards higher resistance. Our results demonstrate how order of appearance of mutations and gene location can influence the rate of resistance evolution.

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Section: Discussionmentioning

confidence: 99%

Lon protease inactivation, or translocation of the lon gene, potentiate bacterial evolution to antibiotic resistance

Nicoloff

Andersson

2013

Molecular Microbiology

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“…Earlier studies reported that E. coli lon mutants are sensitive to colicin (Lee et al, 2006), doxycycline (Girgis et al, 2009) and plant oils (Shapira & Mimran, 2007), but resistant to several antibiotics and organic solvents (Nicoloff & Andersson, 2013;Nicoloff et al, 2007;Watanabe & Doukyu, 2014). A previous study also revealed that lon mutants display a 40-50 % increase in acrAB transcription and high MarA levels (Nicoloff et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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 Dlon 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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Attenuated colicin-based screening to discover and create novel resistance genes

Futai

2014

Journal of Microbiological Methods

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An E. coli lon mutant conferring partial resistance to colicin may reveal a novel role in regulating proteins involved in the translocation of colicin

Cited by 3 publications

References 31 publications

Lon protease inactivation, or translocation of the lon gene, potentiate bacterial evolution to antibiotic resistance

Lon protease inactivation, or translocation of the lon gene, potentiate bacterial evolution to antibiotic resistance

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

Attenuated colicin-based screening to discover and create novel resistance genes

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