Preliminary Communication

Activity of short lipopeptides and conventional antimicrobials against planktonic cells and biofilms formed by clinical strains of Staphylococcus aureus

* Author for correspondence

Faculty of Pharmacy, Medical University of Gdansk, Al. Hallera 107, 80-416 Gdansk, Poland.

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Email the corresponding author at mdawgul@gumed.edu.pl

Wioletta Baranska-Rybak

Faculty of Medicine, Medical University of Gdansk, Debinki 7, 80-211 Gdansk, Poland

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Elzbieta Kamysz

Faculty of Chemistry, University of Gdansk, Sobieskiego 18/19, 80-952 Gdansk, Poland

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Anna Karafova

Faculty of Pharmacy, Medical University of Gdansk, Al. Hallera 107, 80-416 Gdansk, Poland

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Roman Nowicki

Faculty of Medicine, Medical University of Gdansk, Debinki 7, 80-211 Gdansk, Poland

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Wojciech Kamysz

Faculty of Pharmacy, Medical University of Gdansk, Al. Hallera 107, 80-416 Gdansk, Poland

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Published Online:23 Aug 2012https://doi.org/10.4155/fmc.12.100

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Abstract

Background: The therapy for staphylococcal skin diseases is facing several difficulties caused by the growth of biofilms and development of resistant strains. Short synthetic lipopeptides designed on the basis of antimicrobial peptide structure seem to provide an alternative to conventional therapy. The purpose of this study was to synthesize a group of lipopeptides and evaluate their antistaphylococcal activity against biofilms formed by clinical strains of Staphylococcus aureus. Results: The compounds exhibited a strong antibiofilm activity against all the isolates. The maturity of the biofilms has shown a well-defined influence on antimicrobial activity of conventional antimicrobials. Discussion: Results showed that the lipopeptides were promising agents as the time of the culture did not greatly affect their activity.

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

1 Dawson AL, Dellavalle RP, Elston DM. Infectious skin diseases: a review and needs assessment. Dermatol. Clin.30,141–151 (2012).
Medline CASGoogle Scholar
2 Percival SL, Emanuel CH, Cutting KF, Williams DW. Microbiology of the skin and the role of biofilms in infection. Int. Wound J.9(1),14–32 (2011).
MedlineGoogle Scholar
3 Stevens DL, Eron LL. Cellulitis and soft-tissue infections. Ann. Intern. Med.150(1),ITC11 (2009).
MedlineGoogle Scholar
4 Elston DM. Cutaneous manifestations of infectious disease. Med. Clin. N. Am.93,1283–1290 (2009).
MedlineGoogle Scholar
5 Rogers RL, Perkins J. Skin and soft tissue infections. Prim. Care33,697–710 (2006).
MedlineGoogle Scholar
6 Iwatsuki K, Yamasaki O, Morizane S, Oono T. Staphylococcal cutaneus infections: invasion, evasion and aggregation. J. Dermatol. Sci.42,203–214 (2006).
Medline CASGoogle Scholar
7 Schlievert PM, Strandberg KL, Lin YCH, Peterson ML, Leung DYM. Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis. J. Allerg. Clin. Immun.125(1),39–49 (2010).▪ Provides crucial information concerning Staphylococcus aureus and helps to realize its significance for current dermatology.
Medline CASGoogle Scholar
8 Nikolaev YUA, Plakunov VK. Biofilm – ‘city of microbes’ or an analogue of multicellular organisms? Microbiology76(2),125–138 (2007).▪▪ The analogy between biofilms and multicellular organisms, as well as the reasons for biofilm resistance to antibiotics are discussed in this review.
CASGoogle Scholar
9 Potera C. Biofilm dispersing agent rejuvenates older antibiotics. Environ. Health Persp.118(7),a288 (2010).
Google Scholar
10 Shapiro JA, Nguyen VL, Chamberlain NR. Evidence for persisters in Staphylococcus epidermidis RP62a planktonic cultures and biofilms. J. Med. Microbiol.60(Pt 7),950–960 (2011).
Medline CASGoogle Scholar
11 Coenye T, Nelis HJ. In vitro and in vivo model systems to study microbial biofilm formation. J. Microb. Methods83(2),89–105 (2010).
Medline CASGoogle Scholar
12 Vergidis P, Patel R. Novel approaches to the diagnosis, prevention, and treatment of medical device-associated infections. Inf. Dis. Clin. N. Am.26(1),173–186 (2012).
MedlineGoogle Scholar
13 Aslam S, Darouiche RO. Role of antibiofilm-antimicrobial agents in controlling device-related infections. Int. J. Art. Org.34(9),752–758 (2011).
Medline CASGoogle Scholar
14 Berra L. Internally coated endotracheal tubes with silver sulfadiazine in polyurethane to prevent bacterial colonization: a clinical trial. Int. Care Med.34(6),1030–1037 (2008).
Medline CASGoogle Scholar
15 Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell. Microbiol.11(7),1034–1043 (2009).
Medline CASGoogle Scholar
16 Lynch AS, Robertson GT. Bacterial and fungal biofilm infections. Ann. Rev. Med.59,415–428 (2008).
Medline CASGoogle Scholar
17 Hell E, Giske CG, Nelson A, Römling U, Marchini G. Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation of Staphylococcus epidermidis. Lett. Appl. Microbiol.50,211–215 (2010).
Medline CASGoogle Scholar
18 Bruellhoff K, Fiedler J, Möller M, Groll J, Brenner RE. Surface coating strategies to prevent biofilm formation on implant surfaces. Int. J. Art. Org.33(9),646–653 (2010).
Medline CASGoogle Scholar
19 Costa F, Carvalho IF, Montelaro RC, Gomes P, Martins MCL. Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces. Acta Biomater.7(4),1431–1440 (2011).
Medline CASGoogle Scholar
20 Overhage J, Campisano A, Bains M, Torfs EC, Rehm BH, Hancock RE. Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect. Immun.76,4176–4182 (2008).
Medline CASGoogle Scholar
21 Shank EA, Kolter R. Extracellular signaling and multicellularity in Bacillus subtilis. Curr. Opin. Microbiol.14(6),741–747 (2011).
Medline CASGoogle Scholar
22 Belley A, Neesham-Grenon E, McKay G et al. Oritavancin kills stationary-phase and biofilm Staphylococcus aureus cells in vitro. Antimicrob. Agents Chemother.53,918–925 (2009).
Medline CASGoogle Scholar
23 Schauber J, Gallo RL. Antimicrobial peptides and skin immune defense system. J. Allergy Clin. Immunol.124,13–18 (2009).▪▪ Interesting article summarizing the role of antimicrobial peptides (AMPs) in the innate immune system.
Google Scholar
24 Yoshinari M, Kato T, Matsuzaka K, Hayakawa T, Shiba K. Prevention of biofilm formation on titanium surfaces modified with conjugated molecules comprised of antimicrobial and titanium-binding peptides. Biofouling26,103–110 (2010).
Medline CASGoogle Scholar
25 Willcox MD, Hume EB, Aliwarga Y, Kumar N, Cole N. A novel cationic-peptide coating for the prevention of microbial colonization on contact lenses. J. Appl. Microbiol.105,1817–1825 (2008).
Medline CASGoogle Scholar
26 Cirioni O, Giacometti A, Ghiselli R et al. Citropin 1.1-treated central venous catheters improve the efficacy of hydrophobic antibiotics in the treatment of experimental staphylococcal catheter-related infection. Peptides27,1210–1216 (2006).
Medline CASGoogle Scholar
27 Lobos O, Padilla A, Padilla C. In vitro antimicrobial effect of bacteriocin PsVP-10 in combination with chlorhexidine and triclosan against Streptococcus mutans and Streptococcus sobrinus strains. Arch. Oral Biol.54,230–234 (2009).
Medline CASGoogle Scholar
28 Arslan SY, Leung KP, Wu CD. The effect of lactoferrin on oral bacterial attachment. Oral Microbiol. Immunol.24,411–416 (2009).
Medline CASGoogle Scholar
29 Witt KA, Gillespie TJ, Huber JD, Egleton RD, Davis TP. Peptide drug modifications to enhance bioavailability and blood–brain barrier permeability. Peptides22(12),2329–2343 (2001).
Medline CASGoogle Scholar
30 Eckert R. Road to clinical efficacy: challenges and novel strategies for antimicrobial peptide development. Future Microb.66(4),859–862 (2011).▪▪ Presents potential strategies aiming to increase of the stability, reduce the cytotoxicity or improve the antimicrobial activity of AMPs.
Google Scholar
31 Kamysz W, Silvestri C, Cirioni O et al. In vitro activities of the lipopeptides Palmitoyl (Pal)-Lys-Lys-NH₂ and Pal-Lys-Lys alone and in combination with antimicrobial agents against multiresistant Gram-positive cocci. Antimicrob. Agents Chemother.51(1),354–358 (2007).▪ Determined the reason to consider lipopeptides as potential antistaphylococcal agents.
Medline CASGoogle Scholar
32 Cirioni O, Giacometti A, Ghiselli R et al. The lipopeptides Pal-Lys-Lys-NH₂ and Pal-Lys-Lys soaking alone and in combination with intraperitoneal vancomycin prevent vascular graft biofilm in a subcutaneous rat pouch model of staphylococcal infection. Peptides28(6),1299–1303 (2007).▪▪ Results of above mentioned study have encouraged authors to test a larger group of lipopeptides according to their potential antibiofilm activity.
Medline CASGoogle Scholar
33 Makovitzki A, Avrahami D, Shai Y. Ultrashort antibacterial and antifungal lipopeptides. Proc. Natl Acad. Sci. USA103,15997–16002 (2006).▪ Presents the potential of short lipopeptides towards a broad spectrum of microorganisms.
Medline CASGoogle Scholar
34 Makovitzki A, Viterbo A, Brotman Y, Chet I, Shai Y. Inhibition of fungal and bacterial plant pathogens in vitro and in planta with ultrashort cationic lipopeptides. Appl. Environ. Microbiol.73,6629–6636 (2007).
Medline CASGoogle Scholar
35 Vallon-Eberhard A, Makovitzki A, Beauvais A, Latgé JP, Jung S, Shai Y. Efficient clearance of Aspergillus fumigatus in murine lungs by an ultrashort antimicrobial lipopeptide, palmitoyl-Lys-Ala-DAla-Lys. Antimicrob. Agents Chemother.52(9),3118–3126 (2008).
Medline CASGoogle Scholar
36 Barchiesi F et al. In vitro activity of the synthetic lipopeptide PAL-Lys-Lys-NH₂ alone and in combination with antifungal agents against clinical isolates of Cryptococcus neoformans. Peptides28(8),1509–1513 (2007).
Medline CASGoogle Scholar
37 Simonetti O, Arzeni D, Ganzetti G et al. In vitro activity of the lipopeptide derivative (Pal-Lys-Lys-NH), alone and in combination with antifungal agents, against clinical isolates of dermatophytes. Br. J. Dermatol.161(2),249–252 (2009).
Medline CASGoogle Scholar
38 Barchiesi F, Silvestri C, Arzeni D et al.In vitro susceptibility of dermatophytes to conventional and alternative antifungal agents. Med. Mycol.47(3),321–326 (2009).
Medline CASGoogle Scholar
39 Cirioni O. Lipopeptide laur-CKK-NH₂ dimer preserves daptomycin susceptibility and enhances its activity against Enterococcus faecalis. J. Antimicrob. Chemother.66(4),859–862 (2011).
Medline CASGoogle Scholar
40 Pantosti A, Sanchini A, Monaco M. Mechanisms of antibiotic resistance in Staphylococcus aureus. Future Microbiol.2(3),232–334 (2007).
Google Scholar
41 Shore AC, Deasy EC, Slickers P et al. Detection of staphylococcal cassette chromosome mec type XI carrying highly divergent mecA, mecI, mecR1, blaZ, and ccr genes in human clinical isolates of clonal complex 130 methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother.55(8),3765–3773 (2011).
Medline CASGoogle Scholar
42 Gherardi G, De Florio L, Lorino J, Fico L, Dicuonzo G. Macrolide resistance genotypes and phenotypesamong erythromycin-resistant clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci. FEMS Immunol. Med. Microbiol.55,62–67 (2009).
Medline CASGoogle Scholar
43 Mallick SK, Basak S, Bose S. Inducible clindamycin resistance in Staphylococcus aureus – a therapeutic challenge J. Clin. Diag. Res.3,1513–1518 (2009).
CASGoogle Scholar
44 Stevens DL. Treatments for skin and soft-tissue infections due to MDR Gram-positive bacteria. J. Inf.59(1),32–39 (2009).
Google Scholar
45 Siibak T, Peil L, Xiong L, Mankin A, Remme J, Tenson T. Erythromycin- and chloramphenicol-induced ribosomal assembly defects are secondary effects of protein synthesis inhibition. Antimicrob. Agents Chemother.53(2),563–571 (2009).
Medline CASGoogle Scholar
46 McNeil JCH, Hulten KG, Kaplan SL, Mason EO. Mupirocin resistance in Staphylococcus aureus causing recurrent skin and soft tissue infections in children. Antimicrob. Agents Chemother.55(5),2431–2433 (2011).
Medline CASGoogle Scholar
47 Moody MN, Morrison LK, Tyring SK. Retapamulin: what is the role of this topical antimicrobial in the treatment of bacterial infections in atopic dermatitis? Skin Ther. Lett.15(1),1 (2010).
Medline CASGoogle Scholar
48 Farrell DJ, Robbins M, Rhys-Williams W, Love WG. Investigation of the potential for mutational resistance to XF-73, retapamulin, mupirocin, fusidic acid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus isolates during a 55-passage study. Antimicrob. Agents Chemother.55(3),1177–1181 (2011).
Medline CASGoogle Scholar
49 Wertheim HF, Verveer J, Boelens HA et al. Effect of mupirocin treatment on nasal, pharyngeal, and perineal carriage of Staphylococcus aureus in healthy adults. Antimicrob. Agents Chemother.49(4),1465–1467 (2005).
Medline CASGoogle Scholar
50 Howden BP, Grayson ML. Dumb and dumber – the potential waste of a useful antistaphylococcal agent: emerging fusidic acid resistance in Staphylococcus aureus. Clin. Infect. Dis.42,394–400 (2006).
Medline CASGoogle Scholar
51 Castanheira M, Watters AA, Bell JM, Turnidge JD, Jones RN. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. Isolated in North America and Australia, 2007–2008. Antimicrob. Agents Chemother.54(9),3614–3617 (2010).
Medline CASGoogle Scholar
52 Gould JM, Canda R, Esposito S, Gudid F, Harbarth S. Management of serious methicillin-resistant Staphylococcus aureus (MRSA) infections: what are the limits? Int. J. Antimicrob. Agents37,202–209 (2011).
Medline CASGoogle Scholar
53 Gould JM, David MZ, Esposito S et al. New insights into methicillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance. Int. J. Antimicrob. Agents39,96–104 (2012).
Medline CASGoogle Scholar
54 Giacometti A, Cirioni O, Kamysz W et al.In vitro activity and killing effect of uperin 3.6 against Gram-positive cocci isolated from immunocompromised patients. Antimicrob. Agents Chemother.49(9),3933–3936 (2005).
Medline CASGoogle Scholar
55 Giacometti A, Cirioni O, Riva A et al.In vitro activity of aurein 1.2 alone and in combination with antibiotics against Gram-positive nosocomial cocci. Antimicrob. Agents Chemother.51(4),1494–1496 (2007).
Medline CASGoogle Scholar
56 Giacometti A, Cirioni O, Kamysz W et al.In vitro activity of the histatin derivative P-113 against multidrug-resistant pathogens responsible for pneumonia in immunocompromised patients. Antimicrob. Agents Chemother.49(3),1249–1252 (2005).
Medline CASGoogle Scholar
57 Giacometti A, Cirioni O, Kamysz W et al.In vitro activity of MSI-78 alone and in combination with antibiotics against bacteria responsible for bloodstream infections in neutropenic patients. Int. J. Antimicrob. Agents26(3),235–240 (2005).
Medline CASGoogle Scholar
58 Rieg S. Susceptibility of clinical Staphylococcus aureus isolates to innate defense antimicrobial peptides. Microb. Inf.13(8–9),761–765 (2011).
Medline CASGoogle Scholar
59 Sigurdardottir T, Andersson P, Davoudi M, Malmsten M, Schmidtchen A, Bodelsson M. In silico identification and biological evaluation of antimicrobial peptides based on human cathelicidin LL-37. Antimicrob. Agents Chemother.50(9),2983–2989 (2006).
Medline CASGoogle Scholar
60 Baranska-Rybak W, Dawgul M, Bielinska S, Kraska B, Piechowicz L, Kamysz W. Colorimetric evaluation of the time-killing assay for Citropin 1.1, lipopeptide Palm-KK-NH₂, and Temporin A. J. Microbiol. Biotechnol.21(5),536–539 (2011).
Medline CASGoogle Scholar
61 Bowdish DME, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock REW. Impact of LL-37 on anti-infective immunity. J. Leukoc. Biol.77,451–459 (2005).
Medline CASGoogle Scholar
62 Minardi D, Ghiselli R, Cirioni O et al. The antimicrobial peptide Tachyplesin III coated alone and in combination with intraperitoneal piperacillin–tazobactam prevents ureteral stent Pseudomonas infection in a rat subcutaneous pouch model. Peptides28(12),2293–2298 (2007).
Medline CASGoogle Scholar
63 Ghiselli R, Giacometti A, Cirioni O et al. Pretreatment with the protegrin IB-367 affects Gram-positive biofilm and enhances the therapeutic efficacy of linezolid in animal models of central venous catheter infection. JPEN J. Parenter. Enteral Nutr.31(6),463–468 (2007).
Medline CASGoogle Scholar
64 Lewis K. Multidrug tolerance of biofilms and persister cells. Curr. Top Microbiol. Immunol.322,107–132 (2008).
Medline CASGoogle Scholar
65 Lewis K. Persister cells, dormancy and infectious disease. Nat. Rev. Microbiol.5,48–56 (2006).
MedlineGoogle Scholar

Vol. 4, No. 12

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Published online 23 August 2012

Published in print August 2012

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Financial & competing interests disclosure

This work was supported by grants from the Polish Scientific Committee (Project No. N N 405 630638 and N N 405 627 838). The authors are grateful to Pfizer for supplying linezolid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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