Regulators of oxidative stress response genes in Escherichia coli and their functional conservation in bacteria

Chiang, Sarah M.; Schellhorn, Herb E.

doi:10.1016/j.abb.2012.02.007

Cited by 306 publications

(243 citation statements)

References 198 publications

Supporting

Mentioning

237

Contrasting

Unclassified

Order By: Relevance

“…S4); the full complement of reporter constructs is detailed in SI Appendix. In our assay, we focused on the activity of the promoters pOxyS and pSoxS, which are activated by the main regulators of the response to H 2 O 2 and superoxide, OxyR and SoxR, respectively (64). We assessed whether ampicillin or norfloxacin induces expression from a diverse set of promoters; gentamicin was not tested because of the confounding effects of aminoglycosides on GFP reporter assays.…”

Section: Resultsmentioning

confidence: 99%

Antibiotics induce redox-related physiological alterations as part of their lethality

Dwyer

Belenky

Yang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

739

683

View full text Add to dashboard Cite

Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H 2 O 2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H 2 O 2 . We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality.reactive oxygen species | DNA repair | mutagenesis T he increasing incidence of antibiotic-resistant infections coupled with a declining antibiotic pipeline has created a global public health threat (1-6). Therefore there is a pressing need to expand our conceptual understanding of how antibiotics act and to use insights gained from such efforts to enhance our antibiotic arsenal. It has been proposed that different classes of bactericidal antibiotics, regardless of their drug-target interactions, generate varying levels of deleterious reactive oxygen species (ROS) that contribute to cell killing (7,8). This unanticipated notion, built upon important prior work (9-11), has been extended and supported by multiple laboratories investigating wide-ranging drug classes (e.g., β-lactams, aminoglycosides, and fluoroquinolones) and bacterial species (e.g., Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Mycobacterium tuberculosis, Bacillus subtilis, Staphylococcus aureus, Acinetobacter baumannii, Burkholderia cepecia, Streptococcus pneumonia, Enterococcus faecalis) using independent lines of evidence (12-39). Importantly,...

show abstract

Section: Resultsmentioning

confidence: 99%

Antibiotics induce redox-related physiological alterations as part of their lethality

Dwyer

Belenky

Yang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

739

683

View full text Add to dashboard Cite

show abstract

“…Similarly, there are two catalases in E. coli: hydroperoxidase I (HPI) and hydroperoxidase II (HPII), and they are encoded by katG and katE, respectively. The gene katG is part of the H 2 O 2 dependent oxyR regulated response system, while the gene katE is regulated by RpoS independent of H 2 O 2 induction (Mukhopadhyay and Schellhorn, 1994;Chiang and Schellhorn, 2012 (Nachin et al, 2005). However, only a few studies have applied this method to investigate PC inactivation mechanisms (Gao et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…The expression of gene sodC is controlled by another regulator RpoS which is related with stationary phase and general stress, and to our knowledge, the regulation of sodB gene is not elucidated (Storz et al, 1990;Chiang and Schellhorn, 2012). Similarly, there are two catalases in E. coli: hydroperoxidase I (HPI) and hydroperoxidase II (HPII), and they are encoded by katG and katE, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…These ROSs can simultaneously inactivate bacteria and degrade the cellular component or metabolites (Robertson et al, 2012). Another alternative, called a photoelectrocatalytic (PEC) system, applies a potential bias using the immobilized catalyst as a photoanode, enhancing inactivation performance by suppressing h þ and e À recombination (Baram et al, 2007;Li et al, 2011Li et al, , 2015 (Chiang and Schellhorn, 2012). Leung et al (2008) discovered the increase of catalase and SOD activities during PC treatment of marine bacteria, indicating that the oxidative stress responses were induced by the over-production of ROSs during the PC inactivation process.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Unveiling the photoelectrocatalytic inactivation mechanism of Escherichia coli : Convincing evidence from responses of parent and anti-oxidation single gene knockout mutants

Sun

et al. 2016

Water Research

View full text Add to dashboard Cite

“…18 Considering that the RpoS response upregulates pol IV by ~100% and promotes resistance to oxidation, the ability of pol IV to incorporate 8-oxo-dGTP may also be beneficial for survival. 19,20 Although the mode of replication in which pol IV incorporates 8-oxo-dGTP has yet to be elucidated, the suggested high frequency of 8-oxo-dGTP incorporation during antibiotic treatment indicates that pol IV is actively engaged in replication during stress, which may be accounted for by pol IV RDR activity. 18 Taken together, pol IV was probably selected to perform multiple functions in DNA damage tolerance in stressed cells, including RDR, TLS, and 8-oxo-dGMP incorporation.…”

Section: Introductionmentioning

confidence: 99%

DNA polymerases are error-prone at RecA-mediated recombination intermediates

2013

View full text Add to dashboard Cite

G enetic studies have suggested thatY-family translesion DNA polymerase IV (DinB) performs error-prone recombination-directed replication (RDR) under conditions of stress due to its ability to promote mutations during double-strand break (DSB) repair in growth-limited E. coli cells. In recent studies we have demonstrated that pol IV is preferentially recruited to D-loop recombination intermediates at stressinduced concentrations and is highly mutagenic during RDR in vitro. These findings verify longstanding genetic data that have implicated pol IV in promoting stress-induced mutagenesis at D-loops. In this Extra View, we demonstrate the surprising finding that A-family pol I, which normally exhibits high-fidelity DNA synthesis, is highly error-prone at D-loops like pol IV. These findings indicate that DNA polymerases are intrinsically error-prone at RecA-mediated D-loops and suggest that auxiliary factors are necessary for suppressing mutations during RDR in non-stressed proliferating cells.

show abstract

Regulators of oxidative stress response genes in Escherichia coli and their functional conservation in bacteria

Cited by 306 publications

References 198 publications

Antibiotics induce redox-related physiological alterations as part of their lethality

Antibiotics induce redox-related physiological alterations as part of their lethality

Unveiling the photoelectrocatalytic inactivation mechanism of Escherichia coli : Convincing evidence from responses of parent and anti-oxidation single gene knockout mutants

DNA polymerases are error-prone at RecA-mediated recombination intermediates

Contact Info

Product

Resources

About