Skip to main content
SpringerLink
Log in

dinF Elicits Nitric Oxide Signaling Induced by Periplanetasin-4 from American Cockroach in Escherichia coli

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Modern antibiotics have been developed with the aim of destroying cellular function; however, the risk of antibiotic-resistance is increasing continuously. As a result, antimicrobial peptide (AMP) is considered a novel strategy to substitute traditional drugs. This study focused on revealing the antibacterial mechanism(s) of periplanetasn-4, an AMP identified from Cockroach. To elucidate whether periplanetasin-4 generates reactive oxygen species (ROS), a crucial stress factor for cell death, intracellular ROS was measured in Escherichia coli. The degree of membrane and DNA damage was determined using the properties that ROS causes oxidative stress to cell components. Unlike normal cell death, membrane depolarization was observed but DNA fragmentation did not occur. In addition, accumulation of nitric oxide (NO), a free radical with high toxicity, was measured and the byproduct of NO also induced severe intracellular damage. Periplanetasin-4-induced NO also impacted on cytosol calcium levels and triggered lipid peroxidation and DNA oxidation. These features were weakened when NO synthesis was interrupted, and this data suggested that perplanetasin-4-induced NO participates in E. coli cell damage. Moreover, this AMP-induced NO stimulates expression of SOS repair proteins and activation of RecA, a bacterial caspase-like protein. Features of nitrosative damage did not occur especially without dinF gene which is associated with oxidative stress. Therefore, it was indicated that when there is a NO signal, dinF promotes cell death. In conclusion, the combined investigations demonstrated that the antibacterial mechanism(s) of periplanetasin-4 was a NO-induced cell death, and dinF gene is closely related to cell death pathway.

Graphic Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Scott MG et al (2002) The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 169(7):3883–3891

    Article  CAS  PubMed  Google Scholar 

  2. Sperandio B et al (2008) Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression. J Exp Med 205(5):1121–1132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lam SJ et al (2016) Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nat Microbiol 1(11):1–11

    Article  CAS  Google Scholar 

  4. Lázár V et al (2018) Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides. Nat Microbiol 3(6):718–731

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Nizet V (2006) Antimicrobial peptide resistance mechanisms of human bacterial pathogens. Curr Issues Mol Biol 8(1):11

    CAS  PubMed  Google Scholar 

  6. Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55(1):27–55

    Article  CAS  PubMed  Google Scholar 

  7. Tamba Y, Yamazaki M (2005) Single giant unilamellar vesicle method reveals effect of antimicrobial peptide magainin 2 on membrane permeability. Biochemistry 44(48):15823–15833

    Article  CAS  PubMed  Google Scholar 

  8. Mangoni ML et al (2004) Effects of the antimicrobial peptide temporin L on cell morphology, membrane permeability and viability of Escherichia coli. Biochemical Journal 380(3):859–865

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Uyterhoeven ET et al (2008) Investigating the nucleic acid interactions and antimicrobial mechanism of buforin II. FEBS Lett 582(12):1715–1718

    Article  CAS  PubMed  Google Scholar 

  10. Lee H, Hwang JS, Lee DG (2019) Periplanetasin-4, a novel antimicrobial peptide from the cockroach, inhibits communications between mitochondria and vacuoles. Biochem J 476(8):1267–1284

    Article  CAS  PubMed  Google Scholar 

  11. Luiking YC, Engelen MP, Deutz NE (2010) Regulation of nitric oxide production in health and disease. Curr Opin Clin Nutr Metab Care 13(1):97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Crane BR, Sudhamsu J, Patel BA (2010) Bacterial nitric oxide synthases. Annu Rev Biochem 79:445–470

    Article  CAS  PubMed  Google Scholar 

  13. Sudhamsu J, Crane BR (2009) Bacterial nitric oxide synthases: what are they good for? Trends Microbiol 17(5):212–218

    Article  CAS  PubMed  Google Scholar 

  14. Jones ML et al (2010) Antimicrobial properties of nitric oxide and its application in antimicrobial formulations and medical devices. Appl Microbiol Biotechnol 88(2):401–407

    Article  CAS  PubMed  Google Scholar 

  15. Kim H, Lee DG (2020) Nitric oxide–inducing Genistein elicits apoptosis-like death via an intense SOS response in Escherichia coli. Appl Microbiol Biotechnol 104(24):10711–10724

    Article  CAS  PubMed  Google Scholar 

  16. Kim H, Lee DG (2021) Lupeol-induced nitric oxide elicits apoptosis-like death within Escherichia coli in a DNA fragmentation-independent manner. Biochemical Journal 478(4):855–869

    Article  CAS  PubMed  Google Scholar 

  17. Kim I-W et al (2016) De novo transcriptome analysis and detection of antimicrobial peptides of the American cockroach Periplaneta americana (Linnaeus). PLoS One 11(5):e0155304

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Almeida B et al (2007) NO-mediated apoptosis in yeast. J Cell Sci 120(18):3279–3288

    Article  CAS  PubMed  Google Scholar 

  19. Nishimura A, Kawahara N, Takagi H (2013) The flavoprotein Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells. Biochem Biophys Res Commun 430(1):137–143

    Article  CAS  PubMed  Google Scholar 

  20. Baba T et al (2006) Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Molecular systems biology. https://doi.org/10.1038/msb4100050

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lee B, Lee DG (2017) Reactive oxygen species depletion by silibinin stimulates apoptosis-like death in escherichia coli. J Microbiol Biotechnol 27(12):2129–2140

    Article  CAS  PubMed  Google Scholar 

  22. Lee H, Lee DG (2019) SOS genes contribute to Bac8c induced apoptosis-like death in Escherichia coli. Biochimie 157:195–203

    Article  CAS  PubMed  Google Scholar 

  23. Allen SA et al (2010) Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae. Biotechnol Biofuels 3(1):1–10

    Article  CAS  Google Scholar 

  24. Kamat J et al (2000) Reactive oxygen species mediated membrane damage induced by fullerene derivatives and its possible biological implications. Toxicology 155(1–3):55–61

    Article  CAS  PubMed  Google Scholar 

  25. Roos WP, Thomas AD, Kaina B (2016) DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer 16(1):20

    Article  CAS  PubMed  Google Scholar 

  26. Vumma R et al (2016) Antibacterial effects of nitric oxide on uropathogenic Escherichia coli during bladder epithelial cell colonization—a comparison with nitrofurantoin. J Antibiot 69(3):183–186

    Article  CAS  Google Scholar 

  27. Pereira L et al (2017) β-Adrenergic induced SR Ca2+ leak is mediated by an Epac-NOS pathway. J Mol Cell Cardiol 108:8–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Xiong Z-Q et al (2013) The mechanism of antifungal action of a new polyene macrolide antibiotic antifungalmycin 702 from Streptomyces padanus JAU4234 on the rice sheath blight pathogen Rhizoctonia solani. PloS One 8(8):e73884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Michel B (2005) After 30 years of study, the bacterial SOS response still surprises us. PLoS Biol 3(7):e255

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Rodríguez-Beltrán J et al (2012) The Escherichia coli SOS gene dinF protects against oxidative stress and bile salts. PloS one 7(4):e34791

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Peeters SH, de Jonge MI (2018) For the greater good: Programmed cell death in bacterial communities. Microbiol Res 207:161–169

    Article  CAS  PubMed  Google Scholar 

  32. Moges F et al (2016) Cockroaches as a source of high bacterial pathogens with multidrug resistant strains in Gondar town, Ethiopia. BioMed Res Int. https://doi.org/10.1155/2016/2825056

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ali SM et al (2017) Identification and characterization of antibacterial compound (s) of cockroaches (Periplaneta americana). Appl Microbiol Biotechnol 101(1):253–286

    Article  CAS  PubMed  Google Scholar 

  34. Hong J et al (2017) The American cockroach peptide periplanetasin-2 blocks Clostridium Difficile toxin A-induced cell damage and inflammation in the gut. J Microbiol Biotechnol 27(4):694–700

    Article  CAS  PubMed  Google Scholar 

  35. Yoon IN et al (2017) The American cockroach peptide periplanetasin-4 inhibits Clostridium difficile toxin A-induced cell toxicities and inflammatory responses in the mouse gut. J Pept Sci 23(11):833–839

    Article  CAS  PubMed  Google Scholar 

  36. Yun J, Hwang J-S, Lee DG (2017) The antifungal activity of the peptide, periplanetasin-2, derived from American cockroach Periplaneta americana. Biochemical Journal 474(17):3027–3043

    Article  CAS  PubMed  Google Scholar 

  37. Kohanski MA et al (2008) Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death. Cell 135(4):679–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Uhl L, Dukan S (2016) Hydrogen peroxide induced cell death: the major defences relative roles and consequences in E. coli. PloS one 11(8):e0159706

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Smirnova GV et al (2015) Extracellular superoxide provokes glutathione efflux from Escherichia coli cells. Res Microbiol 166(8):609–617

    Article  CAS  PubMed  Google Scholar 

  40. Islam BU et al (2015) Pathophysiological role of peroxynitrite induced DNA damage in human diseases: a special focus on poly (ADP-ribose) polymerase (PARP). Indian J Clin Biochem 30(4):368

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Bicker G (2001) Sources and targets of nitric oxide signalling in insect nervous systems. Cell Tissue Res 303(2):137–146

    Article  CAS  PubMed  Google Scholar 

  42. Bryan NS, Bian K, Murad F (2009) Discovery of the nitric oxide signaling pathway and targets for drug development. Front Biosci 14(1):1–18

    Article  CAS  Google Scholar 

  43. Privett BJ et al (2012) Examination of bacterial resistance to exogenous nitric oxide. Nitric Oxide 26(3):169–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sun C et al (2018) Nitric oxide acts downstream of hydrogen peroxide in regulating aluminum-induced antioxidant defense that enhances aluminum resistance in wheat seedlings. Environ Exp Bot 145:95–103

    Article  CAS  Google Scholar 

  45. Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33(7):829–37

    Article  PubMed  CAS  Google Scholar 

  46. Maslowska KH, Makiela-Dzbenska K, Fijalkowska IJ (2019) The SOS system: a complex and tightly regulated response to DNA damage. Environ Mol Mutagen 60(4):368–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Asplund-Samuelsson J (2015) The art of destruction: revealing the proteolytic capacity of bacterial caspase homologs. Mol Microbiol 98(1):1–6

    Article  CAS  PubMed  Google Scholar 

  48. Brambilla E et al (2018) DnaA and LexA proteins regulate transcription of the uvrB gene in Escherichia coli: the role of DnaA in the control of the SOS regulon. Front Microbiol 9:1212

    Article  PubMed  PubMed Central  Google Scholar 

  49. Janion C (2008) Inducible SOS response system of DNA repair and mutagenesis in Escherichia coli. Int J Biol Sci 4(6):338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Next-Generation BioGreen 21 Program (Project No. PJ01325603), Rural Development Administration, Republic of Korea. This manuscript also has been grammatically edited by a native speaker, a professional editing firm, Enago.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors.

Author information

Author notes

  1. Heejeong Lee and JaeSam Hwang contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Korea

    Heejeong Lee & Dong Gun Lee

  2. Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Wanju, Republic of Korea

    Jae Sam Hwang

Authors
  1. Heejeong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jae Sam Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Gun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H. Lee, J.S. Hwang, and D.G. Lee conceived the study and designed the experiment. H. Lee performed the experiments and collected the data. H. Lee and D.G. Lee analyzed the data. H. Lee wrote the manuscript.

Corresponding author

Correspondence to Dong Gun Lee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (docx 985 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, H., Hwang, J.S. & Lee, D.G. dinF Elicits Nitric Oxide Signaling Induced by Periplanetasin-4 from American Cockroach in Escherichia coli. Curr Microbiol 78, 3550–3561 (2021). https://doi.org/10.1007/s00284-021-02615-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-021-02615-5

Search

Navigation