Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

Xiong,Fu; Dai,Xiaotian; Li,Yu‑Xue; Wei,Rui; An,Li; Wang,Yajuan; Chen,Zhenhong

doi:10.3892/mmr.2019.9988

Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

Authors:
- Fu Xiong
- Xiaotian Dai
- Yu‑Xue Li
- Rui Wei
- Li An
- Yajuan Wang
- Zhenhong Chen
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Affiliations: Department of Pulmonology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China, Department of Respiratory Medicine, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China, Department of Respiratory Medicine, North China University of Science and Technology of Clinical Medicine, Tangshan, Hebei 063000, P.R. China, Department of Nanlou Pulmonology and National Clinical Research Center of Geriatrics Disease, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
Published online on: February 26, 2019 https://doi.org/10.3892/mmr.2019.9988
Pages: 3337-3344

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Abstract

Methicillin‑resistant Staphylococcus aureus (S. aureus; MRSA) is one of the most common bacterial pathogens and MRSA infections are characterized by high mortality rates. Antimicrobial peptides are considered one of the most promising drugs for the treatment of resistant strains of S. aureus. The present study aimed to examine the antimicrobial activity of L12 against numerous bacterial species using the broth microdilution method. Furthermore, the synergistic effect of L12 combined with various antibacterial drugs was tested, and its antibacterial mechanism was investigated by a checkerboard assay. The alterations in bacterial morphology were detected by electron microscopy, and biofilm formation and removal were tested by crystal violet staining. The present results suggested that L12 affected the growth of gram‑positive strains, particularly S. aureus. Electron microscopy analysis suggested that L12 may target the cell membrane, and L12 increased the antibacterial activity of vancomycin and levofloxacin, exerting a synergistic effect. However, the minimal inhibitory concentrations (MICs) of L12 were not correlated with antibiotic resistance, the strains resistant to more antibiotics were not more resistant to L12. A sub‑MIC of L12 was able to inhibit biofilm formation in a dose‑dependent manner; however, concentrations of L12 ≤10 times the MIC were not sufficient to degrade previously formed biofilm. Collectively, the present study suggested that L12 may represent a novel potential therapeutic molecule for the treatment of S. aureus infections.

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1	Palavecino EL: Clinical, epidemiologic, and laboratory aspects of methicillin-resistant Staphylococcus aureus infections. Methods Mol Biol. 1085:1–24. 2014. View Article : Google Scholar : PubMed/NCBI
2	Bassetti M and Righi E: Multidrug-resistant bacteria: What is the threat? Hematology Am Soc Hematol Educ Program. 2013:428–432. 2013. View Article : Google Scholar : PubMed/NCBI
3	Kang HK, Kim C, Seo CH and Park Y: The therapeutic applications of antimicrobial peptides (AMPs): A patent review. J Microbiol. 55:1–12. 2017. View Article : Google Scholar : PubMed/NCBI
4	Zasloff M: Antimicrobial peptides of multicellular organisms. Nature. 415:389–395. 2002. View Article : Google Scholar : PubMed/NCBI
5	Fjell CD, Hiss JA, Hancock RE and Schneider G: Designing antimicrobial peptides: Form follows function. Nat Rev Drug Discov. 11:37–51. 2011. View Article : Google Scholar : PubMed/NCBI
6	Zasloff M: Antibiotic peptides as mediators of innate immunity. Curr Opin Immunol. 4:3–7. 1992. View Article : Google Scholar : PubMed/NCBI
7	Tripathi AK, Kumari T, Tandon A, Sayeed M, Afshan T, Kathuria M, Shukla PK, Mitra K and Ghosh JK: Selective phenylalanine to proline substitution for improved antimicrobial and anticancer activities of peptides designed on phenylalanine heptad repeat. Acta Biomater. 57:170–186. 2017. View Article : Google Scholar : PubMed/NCBI
8	Kazmirchuk T, Dick K, Burnside DJ, Barnes B, Moteshareie H, Hajikarimlou M, Omidi K, Ahmed D, Low A, Lettl C, et al: Designing anti-Zika virus peptides derived from predicted human-Zika virus protein-protein interactions. Comput Biol Chem. 71:180–187. 2017. View Article : Google Scholar : PubMed/NCBI
9	Xia X, Cheng L, Zhang S, Wang L and Hu J: The role of natural antimicrobial peptides during infection and chronic inflammation. Antonie Van Leeuwenhoek. 111:5–26. 2018. View Article : Google Scholar : PubMed/NCBI
10	Ciociola T, Giovati L, Conti S, Magliani W, Santinoli C and Polonelli L: Natural and synthetic peptides with antifungal activity. Future Med Chem. 8:1413–1433. 2016. View Article : Google Scholar : PubMed/NCBI
11	Chen Z, Chang D, Zou Y, Su L, Zhu Y, Fang X, Wang J, Guo Y, Zhao J, Li D, et al: Genome sequence of enterococcus faecium clinical isolate LCT-EF128. J Bacteriol. 194:47652012. View Article : Google Scholar : PubMed/NCBI
12	Ouyang J, Sun F, Feng W, Sun Y, Qiu X, Xiong L, Liu Y and Chen Y: Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa. J Appl Microbiol. 120:966–974. 2016. View Article : Google Scholar : PubMed/NCBI
13	Clinical Laboratory Standards Institute, . Performance Standards for Antimicrobial Susceptibility Testing; 25th Informational Supplement. CLSI document M100-S24. Clinical Laboratory Standards Institute. (Wayne, PA). 2015.
14	Pankey GA and Ashcraft DS: In vitro synergy of ciprofloxacin and gatifloxacin against ciprofloxacin-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 49:2959–2964. 2005. View Article : Google Scholar : PubMed/NCBI
15	Menegucci TC, Albiero J, Migliorini LB, Alves JL, Viana GF, Mazucheli J, Carrara-Marroni FE, Cardoso CL and Tognim MC: Strategies for the treatment of polymyxin B-resistant acinetobacter baumannii infections. Int J Antimicrob Agents. 47:380–385. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wuerth KC, Falsafi R and Hancock REW: Synthetic host defense peptide IDR-1002 reduces inflammation in Pseudomonas aeruginosa lung infection. PloS One. 12:e01875652017. View Article : Google Scholar : PubMed/NCBI
17	Wu X, Li Z, Li X, Tian Y, Fan Y, Yu C, Zhou B, Liu Y, Xiang R and Yang L: Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria. Drug Des Devel Ther. 11:939–946. 2017. View Article : Google Scholar : PubMed/NCBI
18	Bechinger B and Gorr SU: Antimicrobial peptides: Mechanisms of action and resistance. J Dent Res. 96:254–260. 2017. View Article : Google Scholar : PubMed/NCBI
19	Mangoni ML, McDermott AM and Zasloff M: Antimicrobial peptides and wound healing: Biological and therapeutic considerations. Exp Dermatol. 25:167–173. 2016. View Article : Google Scholar : PubMed/NCBI
20	Ge Y, MacDonald DL, Holroyd KJ, Thornsberry C, Wexler H and Zasloff M: In vitro antibacterial properties of pexiganan, an analog of magainin. Antimicrob Agents Chemother. 43:782–788. 1999. View Article : Google Scholar : PubMed/NCBI
21	Wellinghausen N, Chatterjee I, Berger A, Niederfuehr A, Proctor RA and Kahl BC: Characterization of clinical Enterococcus faecalis small-colony variants. J Clin Microbiol. 47:2802–2811. 2009. View Article : Google Scholar : PubMed/NCBI
22	Schillaci D, Cusimano MG, Spinello A, Barone G, Russo D, Vitale M, Parrinello D and Arizza V: Paracentrin 1, a synthetic antimicrobial peptide from the sea-urchin paracentrotus lividus, interferes with Staphylococcal and Pseudomonas aeruginosa biofilm formation. AMB Express. 4:782014. View Article : Google Scholar : PubMed/NCBI
23	Gottschalk S, Gottlieb CT, Vestergaard M, Hansen PR, Gram L, Ingmer H and Thomsen LE: Amphibian antimicrobial peptide fallaxin analogue FL9 affects virulence gene expression and DNA replication in Staphylococcus aureus. J Med Microbiol. 64:1504–1513. 2015. View Article : Google Scholar : PubMed/NCBI
24	Hu Y, Liu A, Vaudrey J, Vaiciunaite B, Moigboi C, McTavish SM, Kearns A and Coates A: Combinations of beta-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus. PloS One. 10:e01176642015. View Article : Google Scholar : PubMed/NCBI
25	Wang Z, Zhang L, Wang J, Wei D, Shi B and Shan A: Synergistic interaction of PMAP-36 and PRW4 with aminoglycoside antibiotics and their antibacterial mechanism. World J Microbiol Biotechnol. 30:3121–3128. 2014. View Article : Google Scholar : PubMed/NCBI
26	Sani MA and Separovic F: Antimicrobial peptide structures: From model membranes to live cells. Chemistry. 24:286–291. 2018. View Article : Google Scholar : PubMed/NCBI
27	Marin-Medina N, Ramirez DA, Trier S and Leidy C: Mechanical properties that influence antimicrobial peptide activity in lipid membranes. Appl Microbiol Biotechnol. 100:10251–10263. 2016. View Article : Google Scholar : PubMed/NCBI
28	Amani J, Barjini KA, Moghaddam MM and Asadi A: In vitro synergistic effect of the CM11 antimicrobial peptide in combination with common antibiotics against clinical isolates of six species of multidrug-resistant pathogenic bacteria. Protein Pept Lett. 22:940–951. 2015. View Article : Google Scholar : PubMed/NCBI
29	Karampatakis V, Papanikolaou T, Giannousis M, Goulas A, Mandraveli K, Kilmpasani M, Alexiou-Daniel S and Mirtsou-Fidani V: Stability and antibacterial potency of ceftazidime and vancomycin eyedrops reconstituted in BSS against Pseudomonas aeruginosa and Staphylococcus aureus. Acta Ophthalmol. 87:555–558. 2009. View Article : Google Scholar : PubMed/NCBI
30	Montanaro L, Speziale P, Campoccia D, Ravaioli S, Cangini I, Pietrocola G, Giannini S and Arciola CR: Scenery of staphylococcus implant infections in orthopedics. Future Microbiol. 6:1329–1349. 2011. View Article : Google Scholar : PubMed/NCBI
31	Stewart EJ, Ganesan M, Younger JG and Solomon MJ: Artificial biofilms establish the role of matrix interactions in staphylococcal biofilm assembly and disassembly. Sci Rep. 5:130812015. View Article : Google Scholar : PubMed/NCBI
32	Domingues MM, Inacio RG, Raimundo JM, Martins M, Castanho MA and Santos NC: Biophysical characterization of polymyxin B interaction with LPS aggregates and membrane model systems. Biopolymers. 98:338–344. 2012. View Article : Google Scholar : PubMed/NCBI
33	Haney EF, Mansour SC and Hancock RE: Antimicrobial peptides: An introduction. Methods Mol Biol. 1548:3–22. 2017. View Article : Google Scholar : PubMed/NCBI