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Molecular Docking, Anti-Biofilm & Antibacterial Activities and Therapeutic Index of mCM11 Peptide on Acinetobacter baumannii Strains

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Abstract

Despite the huge efforts of microbiologists, infectious diseases have yet remained one of the leading causes of death in humans, further highlighting the research priority for controlling opportunistic pathogens. Many researchers have used antibacterial peptides to solve the problem of antibiotic resistance. This research is thus conducted to investigate the antibacterial and anti-biofilm activity of a novel modified cecropin–melittin 11-peptide with improved therapeutic properties and lower side effects. After synthesis and purification of mCM11 (NH2-WRLFRRILRVL-NH2) by solid-phase synthesis and HPLC methods, respectively, the antibacterial and biofilm inhibitory activities were explored in vitro. TMHMM was used to confirm the reaction of mCM11 on the plasma membrane of the prokaryotic cells. The interaction between mCM11 on Acinetobacter baumannii strains was investigated by molecular docking using ClusPro2.0. Hemolysis and therapeutic indexes were also calculated to quantify the relative safety and adverse effects of mCM11. According to the results, mCM11 has a high inhibitory and lethal effect on A. baumannii strains due to its cationic properties and new specific sequence. Molecular docking revealed the release of a significant amount of energy when mCM11 binds to the surface of A. baumannii in an appropriate site. The findings indicated that mCM11 IC50 (4 μg/mL) lysed 2.78% of RBCs; moreover, 8 strains of Acinetobacter baumannii showed a favorable therapeutic index. The mCM11 exhibits strong antibacterial and antibiofilm activities against A. baumannii strains, suggesting its potential therapeutic role in infections caused by these strains. Similar to its impact on A. baumannii, mCM11 could be a suitable alternative to antibiotics in combat against antibiotic-resistant bacteria in the in vivo experiments.

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Data Availability

The results obtained and analyzed during this research have been published only in this paper, and the data are also reproducible and are available upon request from the authors.

Abbreviations

A. b:

Acinetobacter baumannii

A. baumannii :

Acinetobacter baumannii

AMP:

Anti-Microbial Peptide

ATCC:

American Type Culture Collection

BPP:

Biofilm Production Power

CM11:

Cecropin–Melittin 11 peptide

DMRT:

Duncan's Multiple Range Test

E. coli :

Escherichia coli

LBF:

Lack of Biofilm Formation

MBC:

Minimum Bactericidal Concentration

MBF:

Moderately Biofilm Formation

mCM11:

Modified CM11

MDR:

Multi-Drug Resistant

MIC:

Minimum Inhibitory Concentrations

O.D:

Optical Density

ODB:

Optical Density of control sample with Bacteria

ODC:

Optical Density of Control sample without bacteria

ODT:

Optical Density of peptide-Treated sample

PBS:

Phosphate-Buffered saline

PDR:

Pan Drug-Resistant

RBC:

Red Blood Cell

SBF:

Strongly Biofilm Formation

TI:

Therapeutic index

TMHMM:

Tied Mixture Hidden Markov Model

TSB:

Tryptic Soy Broth

WBF:

Weakly Biofilm Formation

WHO:

World Health Organization

XDR:

Extensively Drug-Resistant

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Acknowledgements

This research was carried out using the facilities of IAU, Qom Branch. The authors thank Mohammad Eshtiaghi, Mansoureh Algharnia, Samaneh Banaeian Kalaat, Fahimeh Afzali, Zahraa Karimi, Alborz translation bureau, and Project Sara Ojdanesh Institute.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors.

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Authors and Affiliations

  1. Department of Microbiology, Qom Branch, Islamic Azad University, Qom, Iran

    Sajjad Eshtiaghi & Razieh Nazari

  2. Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mahdi Fasihi-Ramandi

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  1. Sajjad Eshtiaghi
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  2. Razieh Nazari
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  3. Mahdi Fasihi-Ramandi
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Contributions

SE, RN, and MF-R were involved in the design of this study, Laboratory works, Data collection, Statistical analysis, and writing the Draft manuscript. All the authors also cooperated in editing and improving the final version of the article. Design the research: S, R and M. Data collection: S, R and M. Laboratory work: S, R and M. Statistical analysis: S, R and M. Manuscript draft: S, R and M. All authors helped edit and approve the final version of this manuscript for submission. They also contributed to finalizing the manuscript and approved the final draft.

Corresponding author

Correspondence to Razieh Nazari.

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The authors of this study confirm that there is no conflict of interest.

Ethical Approval

The preparation of the A. baumannii strains and samples of this research was approved by the ethics committee of IAU- Qom branch (IR.IAU.QOM.REC.1398.004).

Consent to Participate

In this research entitled "TI Analysis of an mCM11 Peptide; Hemolytic, Antibacterial, and Anti-biofilm Activity on A. baumannii strains", no human or direct sample of human tissue were used.

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Eshtiaghi, S., Nazari, R. & Fasihi-Ramandi, M. Molecular Docking, Anti-Biofilm & Antibacterial Activities and Therapeutic Index of mCM11 Peptide on Acinetobacter baumannii Strains. Curr Microbiol 80, 191 (2023). https://doi.org/10.1007/s00284-023-03217-z

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