Original Paper

Inhibition of Dermal MRSA Colonization by Microalgal Micro- and Nanoparticles
G. Lukowski^a, U. Lindequist^{a, b}, S. Mundt^{a, b}, A. Kramer^c, W.-D. Jülich<sup>a, b

a</sup>Institute of Marine Biotechnology e.V. and Institutes of
^bPharmacy and
^cHygiene and Environmental Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany

Address of Corresponding Author

Skin Pharmacol Physiol 2008;21:98-105 (DOI: 10.1159/000113066)

  Key Words

• Methicillin-resistant Staphylococcus aureus
• Micro- and nanoparticles
• Prevention of colonization
• Animal skin

  Abstract

The aim of this study was to investigate the prevention of the dermal colonization of methicillin-resistant Staphylococcus aureus (MRSA) strains by the application of micro- and nanoparticles called Maresome. Maresome were prepared from selected microalgae by a novel emulsion technique. They contain lipids and all other components of the microalgae in an encapsulated form. It could be shown that Maresome prepared from a cyanobacterial strain of the order Nostocales (Bio33-Maresome) were able to inhibit the dermal colonization of different MRSA strains (North German Epidemic Strain, Col, N315) and even of the vancomycin-resistant strain MU50 in the models 'mouse ear' and 'cow udder teat'. Pretreatment of the skin with Maresome reduced the number of attached MRSA by 3-4 log units in comparison to the control. We assume that a prophylactic skin care with Maresome could complete the multibarrier anti-infectious strategy against MRSA.

Copyright © 2008 S. Karger AG, Basel

  References

1.

Schito GC: The importance of the development of antibiotic resistance in Staphylococcus aureus. Clin Microbiol Infect 2006;12:3-8.

2.

Bertrand X: Methicillin-resistant Staphylococcus aureus in elderly care facilities. Aging Health 2006;2:37-45.

3.

Jenkins SG: Resistance trends in Staphylococcus aureus [Protekt years 1-3 (1999-2002)]. J Chemother 2004;16:83-91.

4.

RKI: Zur MRSA-Situation in Deutschland im Jahr 2003. Epidemiol Bull 2004;42:358-361.

5.

Fachtagung der AG Nosokomiale Infektionen am RKI zur Intensivierung der Umsetzung von Präventionsstrategien bei MRSA. Epidemiol Bull Robert-Koch-Institut 2005;5:31-38.

6.

Wagenvoort JHT: MRSA prevention strategies in European countries. Hyg Med 2006;31:28.

7.

Kampf G, Kramer A: Eradication of methicillin-resistant Staphylococcus aureus with an antiseptic soap and nasal mupirocin among colonized patients - an open uncontrolled clinical trial. Ann Clin Microbiol Antimicrob 2004;3:9-14.

8.

Zastrow KD, Kramer A: Recommendations for isolation and antiseptic sanitation of patients with MRSA colonization or infection; in Kramer A, Behrens-Baumann W (eds): Antiseptic Prophylaxis and Therapy in Ocular Infections: Principles, Clinical Practice and Infection Control. Basel, Karger, 2002, vol 33, pp 250-262.

9.

Lindequist U, Schweder T: Marine biotechnology; in Rehm HJ (ed): Biotechnology, ed 2. Weinheim, Wiley-VCH, 2001, pp 442-473.

10.

De Winder B, Matthijs HCP, Mur LR: The role of water retaining substrata on the photosynthetic response of three drought tolerant phototropic microorganisms isolated from a terrestrial habitat. Arch Microbiol 1989;152:458-462.

11.

Lukowski G, Lindequist U, Mundt S, Jülich WD: Pharmazeutisch oder kosmetisch wirksame Mittel aus lipidhaltigen marinen Organismen. 2003, PCT-03/00747.

12.

Gomes AR, Westh H, De Lencastre H: Origins and evolution of methicillin-resistant Staphylococcus aureus clonal lineages. Antimicrob Agents Chemother 2006;50:3237-3244.

13.

Shafer WM, Iandolo JJ: Genetics of staphylococcal enterotoxin B in methicillin-resistant isolates of Staphylococcus aureus. Infect Immun 1979;25:902-911.

14.

Hiramatsu K: The emergence of Staphylococcus aureus with reduced susceptibility to vancomycin in Japan. Am J Med 1998;104:7-10.

15.

Okonogi K, Noji Y, Kondo M, Imada A, Yokota T: Emergence of methicillin-resistant clones from cephamycin-resistant Staphylococcus aureus.J Antimicrob Chemother 1989;24:637-645.

16.

Gill SR, Fouts DE, Archer GL, Mongodin EF, DeBoy RT, Ravel J, Paulsen IT, Kolonay JF, Brinkac L, Beanan M, Dodson RJ, Daugherty SC, Madupu R, Angiuoli SV, Durkin AS, Haft DH, Vamathevan J, Khouri H, Utterback T, Lee C, Dimitrov G, Jiang L, Qin H, Weidman J, Tran K, Kang K, Hance IR, Nelson KE, Fraser CM: Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J Bacteriol 2005;187:2426-2438.

17.

Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, Cui L, Oguchi A, Aoki Ki, Nagai Y, Lian J, Ito T, Kanamori M, Matsumaru H, Maruyama A, Murakami H, Hosoyama A, Mizutani-Ui Y, Takahashi NK, Sawano T, Inoue R, Kaito C, Sekimizu K, Hirakawa H, Kuhara S, Goto S, Yabuzaki J, Kanehisa M, Yamashita A, Oshima K, Furuya K, Yoshino C, Shiba T, Hattori M, Ogasawara N, Hayashi H, Hiramatsu K: Whole genome sequencing of methicillin-resistant Staphylococcus aureus.Lancet 2001;357:1225-1234.

18.

De Lencastre H, Wu SW, Pinho MG, Ludovice AM, Filipe S, Gardete S, Sobral R, Gill S, Chung M, Tomasz A: Antibiotic resistance as a stress response: complete sequencing of a large number of chromosomal loci in Staphylococcus aureus strain COL that impact on the expression of resistance to methicillin. Microb Drug Resist 1999;5:163-175.

19.

Mundt S, Kreitlow S, Nowotny A, Effmert U: Biochemical and pharmacological investigations of selected cyanobacteria. Int J Hyg Environ Health 2001;203:327-334.

20.

European Pharmacopoeia: Microbiological assay of antibiotics. 5th ed. Council of Europe (COE) - European Directorate for the Quality of Medicines (EDQM). 2005;5.3:188.

21.

Lukowski G, Müller JJ: Potential modelling of acrylic acid copolymer nanoparticles. Int J Pharm 1998;168:173-179.

22.

Dingler A: Solid Lipid Nanoparticles as Colloidal Drug Carriers for Dermal Application; PhD thesis, Free University Berlin, 1998, pp 186-203.

23.

Cross SH, Innes B, Roberts MS, Tsuzuki T, Robertson TA, McCormick P: Human skin penetration of sunscreen nanoparticles: in vitro assessment of a novel micronized zinc oxide formulation. Skin Pharmacol Physiol 2007;20:148-154.

24.

Satou N, Morikawa A, Ohmoto K, Urabe H, Shinzani, H, Wakasa K, Yamaki M: Adhesion of streptococci to saliva-coated and uncoated composite-based resins. J Mat Sci 1996;7:749-752.

25.

Gross M, Cramton SE, Friedrich G, Peschel A: Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. Infect Immun 2001;69:3423-3426.

26.

Nicolaides N: Skin lipids: their biochemical uniqueness. Science 1974;186:19-26.

27.

Nieman C: Influences of trace amounts of fatty acids on the growth of microorganisms. Bacteriol Rev 1954;18:147-161.

28.

Kabara JJ, Swieczkowski DM, Conley AJ, Truant JP: Fatty acids and derivatives as antimicrobial agents. Antimicrob Agents Chemother 1972;2:23-28.

29.

Heczko PB, Lüt R, Hryniewicz W, Neugebauer M, Pulverer G: Susceptibility of Staphylococcus aureus and group A, B, C and G streptococci to free fatty acids. J Clin Microbiol 1979;9:333-335.

30.

Kelsey JA, Bayles KW, Shafii B, McGuire MA: Fatty acids and monoacylglycerols inhibit growth of Staphylococcus aureus. Lipids 2006;41:951-961.

31.

Wille JJ, Kydonieus A: Palmitoleic acid isomer (C16:16) in human skin sebum is effective against gram-positive bacteria. Skin Pharmacol Appl Skin Physiol 2003;16:176-187.

32.

Chamberlain NR, Mehrtens BG, Xiong Z, Kapral FA, Boardman JL, Rearick JI: Correlation of carotenoid production, decreased membrane fluidity, and resistance to oleic acid killing in Staphylococcus aureus 18Z. Infect Immun 1991;59:4332-4337.

33.

Othes S, Pire R: Fatty acid composition of Chlorella and Spirulina microalgae species. J AOAC Int2001;84:1708-1714.

34.

Olszewska M: Molekularbiologische, morphologische und chemotaxonomische Charakterisierung ausgewählter Cyanobakterienstämme; Diploma thesis, Greifswald, 2003, pp 33-46.

35.

Kuroda M, Nagasaki S, Ito R, Ohta T: Sesquiterpene farnesol as a competitive inhibitor of lipase activity of Staphylococcus aureus. FEMS Microbiol Lett 2007;273:28-34.

36.

Foster TJ: Nasal colonization by Staphylococcus aureus. Nat Med 2004;10:447-504.

37.

Clarke SR, Mohamed R, Bian L, Routh AF, Kokai-Kun JF, Mond JJ, Tarkowski A, Foster JS: The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host Microbe 2007;1:199-212.

  Author Contacts

Dr. Gerold Lukowski
Institute of Marine Biotechnology e.V.
Walter-Rathenau-Strasse 49a
DE-17489 Greifswald (Germany)
Tel. +49 3834 864 865, Fax +49 3834 864 885, E-Mail lukowski@uni-greifswald.de

  Article Information

Received: December 1, 2006
Accepted after revision: September 28, 2007
Published online: January 14, 2008
Number of Print Pages : 8
Number of Figures : 6, Number of Tables : 2, Number of References : 37

  Publication Details

Skin Pharmacology and Physiology (Journal of Pharmacological and Biophysical Research)

Vol. 21, No. 2, Year 2008 (Cover Date: March 2008)

Journal Editor: Lademann, J. (Berlin)
ISSN: 1660-5527 (Print), eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP

  Drug Dosage / Copyright

Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.