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Evaluation of a Cationic Antimicrobial Peptide as the New Antibiotic Candidate to Treat Staphylococcus aureus Keratitis

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Abstract

Staphylococcus aureus is a most important reason of bacterial keratitis. The emergence of S. aureus resistance to methicillin necessitates searching for new antimicrobial components for keratitis. CM11 is a cationic peptide with strong antibacterial activity against a range of bacteria. In this study, in vitro bactericidal activity of CM11 was investigated using the time-killing assay. For this purpose, corneal methicillin-resistant S. aureus (MRSA)-infected rabbit models were experimentally developed through intrastromal injection of bacteria. The infected rabbits were treated in three groups by artificial tear, gentamicin, and CM11, and their conjunctiva, iris, and cornea were clinically examined using a slit lamp and histopathological examination. The variance analyses of microbial (colony counts) and pathological examinations on the harvested cornea samples showed a significant improvement in the treated groups (CM11 and gentamicin) compared to the control eyes (P ≤ 0.05). According to findings, CM11 and gentamicin could significantly reduce the CFU in comparison with the group received artificial tear. The mean bacterial counts (log CFU/ml) from corneal culture were 2.1, 5.02, and 8.89 for gentamicin, CM11, and control group, respectively (P ≤ 0.05). The above-mentioned findings displayed the efficacy of CM11 cationic peptide for curing the MRSA-mediated keratitis.

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References

  • Albus U (2012) Guide for the care and use of laboratory animals, 8th edn. SAGE Publications, London

    Google Scholar 

  • Amani J, Barjini AK, Moghaddam M, Asadi A (2015) 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

    Article  CAS  PubMed  Google Scholar 

  • Azad ZM, Moravej H, Fasihi-Ramandi M, Masjedian F, Nazari R, Mirnejad R, Moghaddam MM (2017) In vitro synergistic effects of a short cationic peptide and clinically used antibiotics against drug-resistant isolates of Brucella melitensis. J Med Microbiol 66:919–926

    Article  CAS  Google Scholar 

  • Beisel K, Hazlett L, Berk R (1983) Dominant susceptibility effect on the murine corneal response to Pseudomonas aeruginosa. Proc Soc Exp Biol Med 172:488–491

    Article  CAS  PubMed  Google Scholar 

  • Boman H, Wade D, Boman I, Wåhlin B, Merrifield R (1989) Antibacterial and antimalarial properties of peptides that are cecropin-melittin hybrids. FEBS Lett 259:103–106

    Article  CAS  PubMed  Google Scholar 

  • Brown L (2007) Resistance to ocular antibiotics: an overview. Clin Exp Optom 90:258–262

    Article  PubMed  Google Scholar 

  • Cao Y, Yu RQ, Liu Y, Zhou HX, Song LL, Cao Y (2010) Design, recombinant expression, and antibacterial activity of the cecropins–melittin hybrid antimicrobial peptides. Curr Microbiol 61:169–175

    Article  CAS  PubMed  Google Scholar 

  • Chang VS, Dhaliwal DK, Raju L, Kowalski RP (2015) Antibiotic resistance in the treatment of Staphylococcus aureus keratitis: a 20-year review. Cornea 34:698

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen CH, Lu TK (2020) Development and challenges of antimicrobial peptides for therapeutic applications. Antibiotics 9:24

    Article  CAS  PubMed Central  Google Scholar 

  • Clemens LE et al (2017) Designed host defense peptides for the treatment of bacterial keratitis. Invest Ophthalmol Vis Sci 58:6273–6281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De La Fuente-Núñez C, Cardoso MH, de Souza Cândido E, Franco OL, Hancock RE (2016) Synthetic antibiofilm peptides. Biochim Biophys Acta (BBA) Biomembr 1858:1061–1069

    Article  Google Scholar 

  • Deguchi H et al (2018) The trend of resistance to antibiotics for ocular infection of Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium compared with 10-years previous: a retrospective observational study. PLoS ONE 13:e0203705

    Article  PubMed  PubMed Central  Google Scholar 

  • Durrani AF, Atta S, Bhat A, Mammen A, Dhaliwal D, Kowalski RP, Jhanji V (2020) Methicillin-resistant Staphylococcal aureus keratitis: initial treatment, risk factors, clinical features, and treatment outcomes. Am J Ophthalmol. https://doi.org/10.1016/j.ajo.2020.03.017

    Article  PubMed  Google Scholar 

  • Egrilmez S, Yildirim-Theveny Ş (2020) Treatment-resistant bacterial keratitis: challenges and solutions. Clin Ophthalmol 14:287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Epand RM, Epand RF (2009) Lipid domains in bacterial membranes and the action of antimicrobial agents. Biochim Biophys Acta Biomembr 1788:289–294

    Article  CAS  Google Scholar 

  • Griffith GL, Kasus-Jacobi A, Pereira HA (2017) Bioactive antimicrobial peptides as therapeutics for corneal wounds and infections. Adv Wound Care 6:175–190

    Article  Google Scholar 

  • Hollmann A, Martinez M, Maturana P, Semorile LC, Maffia PC (2018) Antimicrobial peptides: interaction with model and biological membranes and synergism with chemical antibiotics. Front Chem 6:204

    Article  PubMed  PubMed Central  Google Scholar 

  • Holve DL, Gum GG, Pritt SL (2013) Effect of sedation with xylazine and ketamine on intraocular pressure in New Zealand white rabbits. J Am Assoc Lab Anim Sci 52:488–490

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kolar SSN, Luca V, Baidouri H, Mannino G, McDermott AM, Mangoni ML (2015) Esculentin-1a (1-21) NH2: a frog skin-derived peptide for microbial keratitis. Cell Mol Life Sci 72:617–627

    Article  CAS  PubMed  Google Scholar 

  • Lakhundi S, Zhang K (2018) Methicillin-resistant Staphylococcus aureus: molecular characterization, evolution, and epidemiology. Clin Microbiol Rev 31:e00020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lalitha P et al (2017) Trends in antibiotic resistance in bacterial keratitis isolates from South India. Br J Ophthalmol 101:108–113

    Article  PubMed  Google Scholar 

  • Lei J et al (2019) The antimicrobial peptides and their potential clinical applications. Am J Transl Res 11:3919

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mannis MJ (2002) The use of antimicrobial peptides in ophthalmology: an experimental study in corneal preservation and the management of bacterial keratitis. Trans Am Ophthalmol Soc 100:243

    PubMed  PubMed Central  Google Scholar 

  • Miller D (2017) Update on the epidemiology and antibiotic resistance of ocular infections Middle East. Afr J Ophthalmol 24:30

    Google Scholar 

  • Moghaddam MM, Abolhassani F, Babavalian H, Mirnejad R, Barjini KA, Amani J (2012) Comparison of in vitro antibacterial activities of two cationic peptides CM15 and CM11 against five pathogenic bacteria: Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio cholerae, Acinetobacter baumannii, and Escherichia coli. Probiot Antimicrob Proteins 4:133–139

    Article  CAS  Google Scholar 

  • Moghaddam MM, Aghamollaei H, Kooshki H, Barjini KA, Mirnejad R, Choopani A (2015) The development of antimicrobial peptides as an approach to prevention of antibiotic resistance. Rev Med Microbiol 26:98–110

    Article  Google Scholar 

  • Moravej H, Moravej Z, Yazdanparast M, Heiat M, Mirhosseini A, Moosazadeh Moghaddam M, Mirnejad R (2018) Antimicrobial peptides: features, action, and their resistance mechanisms in bacteria. Microbial Drug Resistance 24:747–767

    Article  CAS  PubMed  Google Scholar 

  • Pfalzgraff A, Brandenburg K, Weindl G (2018) Antimicrobial peptides and their therapeutic potential for bacterial skin infections and wounds. Front Pharmacol 9:281

    Article  PubMed  PubMed Central  Google Scholar 

  • Ramandi F, Piranfar V, Nadoushan M, Sarshoori J, Misialek M, Heiat M, Moosazadeh Moghaddam M (2017) Dose-response effects of the CM11 as a short cationic antimicrobial peptide on histopathological and biochemical changes in mice. Curr Chem Biol 11:150–157

    Article  CAS  Google Scholar 

  • Robles-Contreras A, Perez-Cano HJ, Babayan-Sosa A, Baca-Lozada O (2013) Bacterial keratitis infection: a battle between virulence factors and the immune response. Common Eye Infect 85:842–847

    Google Scholar 

  • Sharma A (2018) The pharmacist’s role in managing microbial keratitis. US Pharm 43:27–30

    Google Scholar 

  • Suzuki T (2011) A new target for Staphylococcus aureus associated with keratitis. Cornea 30:S34–S40

    Article  PubMed  Google Scholar 

  • Teweldemedhin M, Gebreyesus H, Atsbaha AH, Asgedom SW, Saravanan M (2017) Bacterial profile of ocular infections: a systematic review. BMC Ophthalmol 17:212

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang N, Yang Q, Tan Y, Lin L, Huang Q, Wu K (2015) Bacterial spectrum and antibiotic resistance patterns of ocular infection: differences between external and intraocular diseases. J Ophthalmol 2015:813979

    PubMed  PubMed Central  Google Scholar 

  • Wayne P (2009) Method for dilution antimicrobial susceptibility tests for bacteria that grow aerobically approved standard CLSI document M07-A8, 8th edn. Clinical and Laboratory Standards Institute (CLSI), Wayne

    Google Scholar 

  • Wilhelmus KR (2001) The Draize eye test. Surv Ophthalmol 45:493–515

    Article  CAS  PubMed  Google Scholar 

  • Yeu E, Hauswirth S (2020) A review of the differential diagnosis of acute infectious conjunctivitis: implications for treatment and management. Clin Ophthalmol 14:805

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Hossein Aghamollaei, Hamidreza Safabakhsh & Khosrow Jadidi

  2. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mehrdad Moosazadeh Moghaddam

  3. Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran

    Hamed Zare

  4. Department of Pharmaceutical Biotechnology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Hamid Bakherad

Authors
  1. Hossein Aghamollaei
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  2. Hamidreza Safabakhsh
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  3. Mehrdad Moosazadeh Moghaddam
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  4. Hamed Zare
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  5. Hamid Bakherad
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  6. Khosrow Jadidi
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Correspondence to Khosrow Jadidi.

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Aghamollaei, H., Safabakhsh, H., Moosazadeh Moghaddam, M. et al. Evaluation of a Cationic Antimicrobial Peptide as the New Antibiotic Candidate to Treat Staphylococcus aureus Keratitis. Int J Pept Res Ther 27, 755–762 (2021). https://doi.org/10.1007/s10989-020-10126-3

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  • DOI: https://doi.org/10.1007/s10989-020-10126-3

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