Skip to main content

Advertisement

SpringerLink
Log in

Involvement of outer membrane proteins and peroxide-sensor genes in Burkholderia cepacia resistance to isothiazolone

  • Original Paper
  • Published:
World Journal of Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Isothiazolones are used as preservatives in various modern industrial products. Although microorganisms that exhibit resistance towards these biocides have been identified, the underlying resistance mechanisms are still unclear. Therefore, we investigated the resistance properties of the following Burkholderia cepacia strains to Kathon (a representative of isothiazolones): a wild-type (WT) strain; a laboratory resistance strain (BC-IR) induced from WT; and an isolated strain (BC-327) screened from industrial contamination samples. The bacterial cell structure was disrupted by 50 μg ml−1 Kathon treatment. BC-IR and BC-327 did not display resistance in the presence of 1 ml L−1 Tween 80, 1 ml L−1 Triton X-100, 0.1 % sodium dodecyl sulfate or 1 mmol L−1 EDTA-2Na. Additionally, BC-IR and BC-327 exhibited lower relative conductivity from 10 to 180 min. The types as well as the levels of outer-membrane proteins (OMPs) were altered among WT, BC-IR and BC-327. Finally, the two Kathon-resistance strains BC-IR and BC-327 presented higher resistance capacity to H2O2. We measured the levels of peroxide-sensor genes and observed that the transcriptional activator oxyR, superoxide dismutase sod1, sod2, catalase cat1 and cat3 were all up-regulated under oxidative conditions for all strains. Taken together, OMPs and peroxide-sensor genes in B. cepacia contributed to isothiazolone resistance; However, the laboratory strain BC-IR exhibited a different resistance mechanism and properties compared to the isolated strain BC-327.

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

  • Adibpour N, Khalaj A, Rezaee S, Daneshtalab M (2007) In vitro antifungal activity of 2-(4-substituted phenyl)-3(2H)-isothiazolones. Folia Microbiol 52:573–576

    Article  CAS  Google Scholar 

  • Adibpour N, Khalaj A, Rajabalian S (2010) Synthesis and antibacterial activity of isothiazolyl oxazolidinones and analogous 3(2H)-isothiazolones. Eur J Med Chem 45:19–24

    Article  CAS  Google Scholar 

  • Bogman K, Erne-Brand F, Alsenz J, Drewe J (2003) The role of surfactants in the reversal of active transport mediated by multidrug resistance proteins. J Pharm Sci 92:1250–1261

    Article  CAS  Google Scholar 

  • Brözel VS, Cloete TE (1994) Resistance of Pseudomonas aeruginosa to isothiazolone. J Appl Bacteriol 76:576–582

    Article  Google Scholar 

  • Chapman JS, Diehl MA (1995) Methylchloroisothiazolone-induced growth inhibition and lethality in Escherichia coli. J Appl Microbiol 78:134–141

    CAS  Google Scholar 

  • Chapman JS, Diehl MA, Fearnside KB (1998) Preservative tolerance and resistance. Int J Cosmet Sci 20:31–39

    Article  CAS  Google Scholar 

  • Cheng JJ, Thanassi JA, Thoma CL, Bradbury BJ, Deshpande M, Pucci MJ (2007) Dual targeting of DNA gyrase and topoisomerase IV: target interactions of heteroaryl isothiazolones in Staphylococcus aureus. Antimicrob Agents Chemother 51:2445–2453

    Article  CAS  Google Scholar 

  • Cloete TE (2003) Resistance mechanisms of bacteria to antimicrobial compounds. Int Biodeterior Biodegradation 51:277–282

    Article  CAS  Google Scholar 

  • Collier PJ, Austin P, Gilbert P (1990a) Uptake and distribution of some isothiazolone biocides into Escherichia coli ATCC 8739 and Schizosaccharomyces pombe NCYC 1354. Int J Pharm 66:201–206

    Article  CAS  Google Scholar 

  • Collier PJ, Ramsey AJ, Austin P, Gilbert P (1990b) Growth inhibitory and biocidal activity of some isothiazolone biocides. J Appl Microbiol 69:569–577

    CAS  Google Scholar 

  • Collier PJ, Austin P, Gilbert P (1991) Isothiazolone biocides: enzyme-inhibiting pro-drugs. Int J Pharm 74:195–201

    Article  CAS  Google Scholar 

  • El Abdellaoui H, Varaprasad CVNS, Barawkar D, Chakravarty S, Maderna A, Tam R, Chen HM, Allan M, Wu JZ, Appleby T, Yan SQ, Zhang WJ, Lang S, Yao NH, Hamatake R, Hong Z (2006) Identification of isothiazole-4-carboxamidines derivatives as a novel class of allosteric MEK1 inhibitors. Bioorg Med Chem Lett 16:5561–5566

    Article  CAS  Google Scholar 

  • Ettorre A, Andreassi M, Anselmi C, Neri P, Andreassi L, Di Stefano A (2003) Involvement of oxidative stress in apoptosis induced by a mixture of isothiazolinones in normal human keratinocytes. J Invest Dermatol 121:328–336

    Article  CAS  Google Scholar 

  • Furdas SD, Shekfeh S, Bissinger EM, Wagner JM, Schlimme S, Valkov V, Hendzel M, Jung M, Sippl W (2011) Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors. Bioorgan Med Chem 19:3678–3689

    Article  CAS  Google Scholar 

  • Gedi V, Moon JY, Lim WM, Lee MY, Lee SC, Koo BS, Govindwar S, Yoon MY (2011) Identification and characterization of inhibitors of Haemophilus influenzae acetohydroxyacid synthase. Enzyme Microb Technol 49:1–5

    Article  CAS  Google Scholar 

  • Greenberg JT, Demple B (1986) Glutathione in Escherichia coli is dispensable for resistance to H2O2 and gamma radiation. J Bacteriol 168:1026–1029

    CAS  Google Scholar 

  • Howard-Flanders P, Theriot L (1966) Mutants of Escherichia coli K-12 defective in DNA repair and in genetic recombination. Genetics 53:1137–1150

    CAS  Google Scholar 

  • Jimenez L, Smalls S (2000) Molecular detection of Burkholderia cepacia in toiletry, cosmetic, and pharmaceutical raw materials and finished products. J AOAC Int 83:963–966

    CAS  Google Scholar 

  • Khalaj A, Adibpour N, Shahverdi AR, Daneshtalab M (2004) Synthesis and antibacterial activity of 2-(4-substituted phenyl)-3(2H)-isothiazolones. Eur J Med Chem 39:699–705

    Article  CAS  Google Scholar 

  • King A, Lodola A, Carmi C, Fu J, Mor M, Piomelli D (2009) A critical cysteine residue in monoacylglycerol lipase is targeted by a new class of isothiazolinone-based enzyme inhibitors. Brit J Pharmacol 157:974–983

    Article  CAS  Google Scholar 

  • Kiselyov AS, Semenova M, Semenov VV (2009) 3, 4-Disubstituted isothiazoles: novel potent inhibitors of VEGF receptors 1 and 2. Bioorg Med Chem Lett 19:1195–1198

    Article  CAS  Google Scholar 

  • Leive L (1968) Studies on the permeability change produced in coliform bacteria by ethylenediaminetetraacetate. J Biol Chem 243:2373–2380

    CAS  Google Scholar 

  • Lewin C, Doherty C, Govan J (1993) In vitro activities of meropenem, PD 127391, PD 131628, ceftazidime, chloramphenicol, co-trimoxazole, and ciprofloxacin against Pseudomonas cepacia. Antimicrob Agents Chemother 37:123–125

    Article  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-[Delta][Delta] CT method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Palleroni NJ (2005) Genus I. Burkholderia. In: Garrity GM (ed) Bergey's manual of systematic bacteriology, 2nd edn. Volume 2: The Proteobacteria, Part C: The Alpha-, Beta-, Delta-, and Epsilonproteobacteria. Springer, New York, pp 575-600

  • Pedras MS, Suchy M (2006) Design, synthesis, and antifungal activity of inhibitors of brassilexin detoxification in the plant pathogenic fungus Leptosphaeria maculans. Bioorg Med Chem 14:714–723

    Article  CAS  Google Scholar 

  • Pucci MJ, Cheng JJ, Podos SD, Thoma CL, Thanassi JA, Buechter DD, Mushtaq G, Vigliotti GA, Bradbury BJ, Deshpande M (2007) In vitro and in vivo antibacterial activities of heteroaryl isothiazolones against resistant gram-positive pathogens. Antimicrob Agents Chemother 51:1259–1267

    Article  CAS  Google Scholar 

  • Pucci MJ, Podos SD, Thanassi JA, Leggio MJ, Bradbury BJ, Deshpande M (2011) In vitro and in vivo profiles of ACH-702, an isothiazoloquinolone, against bacterial pathogens. Antimicrob Agents Chemother 55:2860–2871

    Article  CAS  Google Scholar 

  • Reddy BM, Tanneeru K, Meetei PA, Guruprasad L (2011) 3D-QSAR and molecular docking studies on substituted isothiazole analogs as inhibitors against MEK-1 kinase. Chem Biol Drug Des 79:84–91

    Article  Google Scholar 

  • Rushton L, Sass A, Baldwin A, Dowson CG, Donoghue D, Mahenthiralingam E (2013) Key role for efflux in the preservative susceptibility and adaptive resistance of Burkholderia cepacia complex bacteria. Antimicrob Agents Chemother 57:2972–2980

    Article  CAS  Google Scholar 

  • Sharmeen L, McQuade T, Heldsinger A, Gogliotti R, Domagala J, Gracheck S (2001) Inhibition of the early phase of HIV replication by an isothiazolone, PD 161374. Antiviral Res 49:101–114

    Article  CAS  Google Scholar 

  • Speksnijder P, van Ravestijn J, de Voogt P (2010) Trace analysis of isothiazolinones in water samples by large-volume direct injection liquid chromatography tandem mass spectrometry. J Chromatogr A 1217:5184–5189

    Article  CAS  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  CAS  Google Scholar 

  • Tang QY, Feng MG (2007) DPS data processing system: experimental design, statistical analysis and data mining. Science Press, Beijing

    Google Scholar 

  • Tattawasart U, Maillard JY, Furr JR, Russell AD (2000) Outer membrane changes in Pseudomonas stutzeri resistant to chlorhexidine diacetate and cetylpyridinium chloride. Int J Antimicrob Agents 16:233–238

    Article  CAS  Google Scholar 

  • Vermis K, Vandamme P, Nelis HJ (2003) Burkholderia cepacia complex genomovars: utilization of carbon sources, susceptibility to antimicrobial agents and growth on selective media. J Appl Microbiol 95:1191–1199

    Article  CAS  Google Scholar 

  • Vicentini CB, Romagnoli C, Manfredini S, Rossi D, Mares D (2011) Pyrazolo [3, 4-c]isothiazole and isothiazolo [4, 3-d]isoxazole derivatives as antifungal agents. Pharm Biol 49:545–552

    Article  CAS  Google Scholar 

  • Williams TM (2007) The mechanism of action of isothiazolone biocide. Power Plant Chem 9:14–22

    CAS  Google Scholar 

  • Winder CL, Al-Adham IS, Abdel Malek SM, Buultjens TE, Horrocks AJ, Collier PJ (2000) Outer membrane protein shifts in biocide-resistant Pseudomonas aeruginosa PAO1. J Appl Microbiol 89:289–295

    Article  CAS  Google Scholar 

  • Woodcock D, Linsenmeyer M, Chojnowski G, Kriegler A, Nink V, Webster L, Sawyer W (1992) Reversal of multidrug resistance by surfactants. Br J Cancer 66:62

    Article  CAS  Google Scholar 

  • Xu FL, Lin Q, Hou BR (2009) Synthesis and bioactivity of novel benzisothiazolone derivatives as potential microbiocides. J Heterocycl Chem 46:320–323

    Article  CAS  Google Scholar 

  • Yabuuchi E, Kosako Y, Oyaizu H, Yano I, Hotta H, Hashimoto Y, Ezaki T, Arakawa M (1992) Proposal of Burkholderia gen. nov; and transfer of seven species of the Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov. Microbiol Immunol 36:1251–1275

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was funded by Scientific and Technological Project of Guangdong Province (No. 2011B010500024), Strategic Cooperation Projects Guangdong Province and Chinese Academy (No. 2011B090300018) and Young Foundation of Guangdong Academy of Sciences for Scientific Research (No. qnjj201203).

Author information

Authors and Affiliations

  1. State Key Laboratory of Applied Microbiology, South China (The Ministry-Province Joint Development), Guangdong Institute of Microbiology, Guangzhou, 510070, Guangdong, People’s Republic of China

    Gang Zhou, Qing-shan Shi, You-sheng Ouyang & Yi-ben Chen

Authors
  1. Gang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing-shan Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. You-sheng Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi-ben Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing-shan Shi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, G., Shi, Qs., Ouyang, Ys. et al. Involvement of outer membrane proteins and peroxide-sensor genes in Burkholderia cepacia resistance to isothiazolone. World J Microbiol Biotechnol 30, 1251–1260 (2014). https://doi.org/10.1007/s11274-013-1538-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11274-013-1538-3

Keywords

Search

Navigation