Skip to main content

Advertisement

SpringerLink
Log in

Global transcriptome analysis of the Mycobacterium bovis BCG response to sodium hypochlorite

  • Genomics and Proteomics
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Tuberculosis is a common and often deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis and infrequently by other subspecies of the M. tuberculosis complex, such as M. bovis. Sodium hypochlorite (bleach) is routinely used in hospitals and health care facilities for surface sterilization; however, the modes of action of bleach on M. bovis BCG and how this organism develops resistance to sodium hypochlorite have not been elucidated. In this study, we performed a global toxicogenomic analysis of the M. bovis response to 2.5 mM sodium hypochlorite after 10 and 20 min. M. bovis BCG growth was monitored by measuring the quantity of ATP in picomoles produced over a short exposure time (10–60 min) to sodium hypochlorite. This study revealed significant regulation of oxidative stress response genes of M. bovis BCG, such as oxidoreductase, peroxidase, heat shock proteins and lipid transport, and metabolism genes. We interpreted this response as a potentially more lethal interplay between fatty acid metabolism, sulfur metabolism, and oxidative stress. Our results also suggest that sodium hypochlorite repressed transcription of genes involved in cell wall synthesis of M. bovis. This study shows that the treatment of M. bovis BCG with bleach inhibits the biosynthesis of outer cell wall mycolic acids and also induces oxidative damage.

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

Similar content being viewed by others

References

  • Affymetrix (2004) Affymetrix GeneChip® expression analysis technical manual. Affymetrix, Inc, Santa Clara

    Google Scholar 

  • Albrich JM, Hurst JK (1982) Oxidative inactivation of Escherichia coli by hypochlorous acid. Rates and differentiation of respiratory from other reaction sites. FEBS Lett 144:157–161

    CAS  PubMed  Google Scholar 

  • Banu S, Honore N, Saint-Joanis B, Philpott D, Prevost MC, Cole ST (2002) Are the PE-PGRS proteins of Mycobacterium tuberculosis variable surface antigens? Mol Microbiol 44:9–19

    Article  CAS  PubMed  Google Scholar 

  • Barry CE 3rd, Lee RE, Mdluli K, Sampson AE, Schroeder BG, Slayden RA, Yuan Y (1998) Mycolic acids: structure, biosynthesis and physiological functions. Prog Lipid Res 37:143–179

    Article  CAS  PubMed  Google Scholar 

  • Brennan MJ, Delogu G, Chen Y, Bardarov S, Kriakov J, Alavi M, Jacobs WR Jr (2001) Evidence that mycobacterial PE_PGRS proteins are cell surface constituents that influence interactions with other cells. Infect Immun 69:7326–7333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cahn P, Perez H, Ben G, Ochoa C (2003) Tuberculosis and HIV: a partnership against the most vulnerable. J Int Assoc Physicians AIDS Care (Chic Ill) 2:106–123

    Article  Google Scholar 

  • Cain KP, Benoit SR, Winston CA, Mac Kenzie WR (2008) Tuberculosis among foreign-born persons in the United States. Jama 300:405–412

    Article  CAS  PubMed  Google Scholar 

  • Candeias LP, Patel KB, Stratford MR, Wardman P (1993) Free hydroxyl radicals are formed on reaction between the neutrophil-derived species superoxide anion and hypochlorous acid. FEBS Lett 333:151–153

    Article  CAS  PubMed  Google Scholar 

  • Chang W, Small DA, Toghrol F, Bentley WE (2005) Microarray analysis of Pseudomonas aeruginosa reveals induction of pyocin genes in response to hydrogen peroxide. BMC Genomics 6:115

    PubMed  PubMed Central  Google Scholar 

  • Chang W, Small DA, Toghrol F, Bentley WE (2006a) Global transcriptome analysis of Staphylococcus aureus response to hydrogen peroxide. J Bacteriol 188:1648–1659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang W, Toghrol F, Bentley WE (2006b) Toxicogenomic response of Staphylococcus aureus to peracetic acid. Environ Sci Technol 40:5124–5131

    Article  CAS  PubMed  Google Scholar 

  • Chang MW, Toghrol F, Bentley WE (2007) Toxicogenomic response to chlorination includes induction of major virulence genes in Staphylococcus aureus. Environ Sci Technol 41:7570–7575

    Article  CAS  PubMed  Google Scholar 

  • Cole ST (2002) Comparative and functional genomics of the Mycobacterium tuberculosis complex. Microbiology 148:2919–2928

    Article  CAS  PubMed  Google Scholar 

  • Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544

    Article  CAS  PubMed  Google Scholar 

  • Danilchanka O, Mailaender C, Niederweis M (2008) Identification of a novel multidrug efflux pump of Mycobacterium tuberculosis. Antimicrob Agents Chemother 52:2503–2511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delogu G, Brennan MJ (2001) Comparative immune response to PE and PE_PGRS antigens of Mycobacterium tuberculosis. Infect Immun 69:5606–5611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dosanjh NS, Rawat M, Chung JH, Av-Gay Y (2005) Thiol specific oxidative stress response in Mycobacteria. FEMS Microbiol Lett 249:87–94

    Article  CAS  PubMed  Google Scholar 

  • Dubnau E, Chan J, Raynaud C, Mohan VP, Laneelle MA, Yu K, Quemard A, Smith I, Daffe M (2000) Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol Microbiol 36:630–637

    Article  CAS  PubMed  Google Scholar 

  • Dukan S, Touati D (1996) Hypochlorous acid stress in Escherichia coli: resistance, DNA damage, and comparison with hydrogen peroxide stress. J Bacteriol 178:6145–6150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Espinal MA (2003) The global situation of MDR-TB. Tuberculosis (Edinb) 83:44–51

    Article  Google Scholar 

  • Espitia C, Laclette JP, Mondragon-Palomino M, Amador A, Campuzano J, Martens A, Singh M, Cicero R, Zhang Y, Moreno C (1999) The PE-PGRS glycine-rich proteins of Mycobacterium tuberculosis: a new family of fibronectin-binding proteins? Microbiology 145(Pt 12):3487–3495

    Article  CAS  PubMed  Google Scholar 

  • Fox BG, Lyle KS, Rogge CE (2004) Reactions of the diiron enzyme stearoyl-acyl carrier protein desaturase. Acc Chem Res 37:421–429

    Article  CAS  PubMed  Google Scholar 

  • Gomez JE, McKinney JD (2004) M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb) 84:29–44

    Article  Google Scholar 

  • Graham JE, Clark-Curtiss JE (1999) Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS). Proc Natl Acad Sci U S A 96:11554–11559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holmgren A (1989) Thioredoxin and glutaredoxin systems. J Biol Chem 264:13963–13966

    CAS  PubMed  Google Scholar 

  • Imlay JA, Linn S (1986) Bimodal pattern of killing of DNA-repair-defective or anoxically grown Escherichia coli by hydrogen peroxide. J Bacteriol 166:519–527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang HJ, Chang MW, Toghrol F, Bentley WE (2008) Microarray analysis of toxicogenomic effects of triclosan on Staphylococcus aureus. Appl Microbiol Biotechnol 78:695–707

    Article  CAS  PubMed  Google Scholar 

  • Khan AU, Kasha M (1994a) Singlet molecular oxygen evolution upon simple acidification of aqueous hypochlorite: application to studies on the deleterious health effects of chlorinated drinking water. Proc Natl Acad Sci U S A 91:12362–12364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan AU, Kasha M (1994b) Singlet molecular oxygen in the Haber-Weiss reaction. Proc Natl Acad Sci U S A 91:12365–12367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller RA, Britigan BE (1997) Role of oxidants in microbial pathophysiology. Clin Microbiol Rev 10:1–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nordberg J, Arner ES (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31:1287–1312

    Article  CAS  PubMed  Google Scholar 

  • Pasterkamp H (2001) Of Microsoft and mycobacteria. Can J Infect Dis 12:72–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pym AS, Cole ST (1999) Post DOTS, post genomics: the next century of tuberculosis control. Lancet 353:1004–1005

    Article  CAS  PubMed  Google Scholar 

  • Shimakata T, Fujita Y, Kusaka T (1980) Involvement of one of two enoyl-CoA hydratases and enoyl-CoA reductase in the acetyl-CoA-dependent elongation of medium chain fatty acids by Mycobacterium smegmatis. J Biochem 88:1051–1058

    Article  CAS  PubMed  Google Scholar 

  • Singh VK, Moskovitz J, Wilkinson BJ, Jayaswal RK (2001) Molecular characterization of a chromosomal locus in Staphylococcus aureus that contributes to oxidative defence and is highly induced by the cell-wall-active antibiotic oxacillin. Microbiology 147:3037–3045

    Article  CAS  PubMed  Google Scholar 

  • Small DA, Chang W, Toghrol F, Bentley WE (2007a) Comparative global transcription analysis of sodium hypochlorite, peracetic acid, and hydrogen peroxide on Pseudomonas aeruginosa. Appl Microbiol Biotechnol 76:1093–1105

    Article  CAS  PubMed  Google Scholar 

  • Small DA, Chang W, Toghrol F, Bentley WE (2007b) Toxicogenomic analysis of sodium hypochlorite antimicrobial mechanisms in Pseudomonas aeruginosa. Appl Microbiol Biotechnol 74:176–185

    Article  CAS  PubMed  Google Scholar 

  • U.S. Food and Drug Administration (2003) Indirect food additives: adjuvants, production aids, and sanitizers 21 C.F.R. U.S. Food and Drug Administration, Washington D.C.

  • Wilson T, de Lisle GW, Marcinkeviciene JA, Blanchard JS, Collins DM (1998) Antisense RNA to ahpC, an oxidative stress defence gene involved in isoniazid resistance, indicates that AhpC of Mycobacterium bovis has virulence properties. Microbiology 144(Pt 10):2687–2695

    Article  CAS  PubMed  Google Scholar 

  • Winter J, Ilbert M, Graf PC, Ozcelik D, Jakob U (2008) Bleach activates a redox-regulated chaperone by oxidative protein unfolding. Cell 135:691–701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan Y, Lee RE, Besra GS, Belisle JT, Barry CE 3rd (1995) Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 92:6630–6634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research is supported by the US Environmental Protection Agency Grant number T-83284001-2. Although the research described in this paper has been funded wholly by the US Environmental Protection Agency, it has not been subjected to the Agency’s peer and administrative review and, therefore, may not necessarily reflect the views of the EPA nor does the mention of trade names or commercial products constitute endorsement of recommendation of use.

Author information

Authors and Affiliations

  1. Department of Biochemistry, College of Oriental Medicine, Kyung Hee University, Seoul, 130–701, Republic of Korea

    Hyeung-Jin Jang

  2. Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, MD, 20742, USA

    Chantal Nde & William E. Bentley

  3. Microarray Research Laboratory, Biological and Economic Analysis Division, Office of Pesticide Programs, US Environmental Protection Agency, Fort Meade, MD, 20755, USA

    Freshteh Toghrol

Authors
  1. Hyeung-Jin Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chantal Nde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Freshteh Toghrol
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William E. Bentley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Freshteh Toghrol.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplement Figure 1

Standard curve showing the correlation between ATP measurements in relative light units (RLU) and picomoles (GIF 141 Kb).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jang, HJ., Nde, C., Toghrol, F. et al. Global transcriptome analysis of the Mycobacterium bovis BCG response to sodium hypochlorite. Appl Microbiol Biotechnol 85, 127–140 (2009). https://doi.org/10.1007/s00253-009-2208-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-009-2208-0

Keywords

Search

Navigation