Full length articleOctominin: An antibacterial and anti-biofilm peptide for controlling the multidrug resistance and pathogenic Streptococcus parauberis
Graphical abstract
Introduction
Antimicrobial peptides (AMPs) are defense molecules produced by a variety of microbes, plants, and animals, which act against pathogenic viruses, bacteria, fungi, and parasites. In addition, most AMPs have multiple functions, such as anticancer, anti-inflammatory, and immunomodulatory actions [1]. AMPs can act against pathogenic microbes alone, or synergistically with other antimicrobials, showing different modes of actions, including morphological changes, membrane permeability alteration, reactive oxygen species (ROS) generation, antibiofilm activity, DNA damage, and inhibition of protein synthesis [2,3]. Even though pathogenic microbes develop resistance toward antibiotics rapidly, resistance development for AMPs is limited due to their multiple modes of actions and inhibitory activity against multiple classes of pathogens [4]. AMPs are either natural or synthetic; they differ from each other with respect to amino acid sequence, molecular weight, secondary and tertiary structure, yet almost all AMPs share common characteristics, including net charge, higher hydrophobicity, and amphipathic nature [5]. Because of these specific characteristics, AMPs exhibit a relatively low toxicity toward the host, and subsequently produce specific and efficient antimicrobial actions [6]. Although current findings showed that AMPs exhibit a broad spectrum of antimicrobial activity, most AMPs have only been tested against gram-negative bacteria, and limited data are available for those that control gram-positive infections [7]. Therefore, there is an urgent need to discover or synthesize AMPs that control infections caused by gram-positive bacteria and derive their mechanisms of action.
Streptococcosis is a common bacterial infective disease in fish presenting with hemorrhagic septicemia, meningitis, abdominal distention, etc. S. parauberis, which was introduced by Williams and Collins (1990), is one of the major causative bacteria for streptococcosis, and is classified as S. uberis genotype II. S. parauberis is a gram-positive, non-motile, alpha-hemolytic, cocci bacterium that mainly infects rainbow trout (Oncorhynchus mykiss) and olive flounder (Paralichthys olivaceus) [8]. In a number of previous studies, S. parauberis was identified as an antibiotic resistant bacterium. The S. parauberis strain, which was found in an olive flounder from a fish farm in Republic of Korea, had high resistance to multiple antibiotics, including amikacin, ciprofloxacin, and kanamycin [9]. Moreover, S. parauberis is capable of forming biofilms, which can be considered as one of its major defense mechanisms against commercially available antibiotics, and promotes the development of antibiotic resistance [10]. Therefore, a promising novel drug candidate is essential for the control of S. parauberis infections.
Since invertebrates lack an adaptive immunity, AMPs play a significant role in their innate immunity to protect against pathogenic microorganisms. Several studies have been conducted on invertebrates including, Cornu aspersum [11], Helix lucorum [12], and Rapana venosa [13], for their self-synthesized AMPs. In contrast, marine invertebrates, such as tunicates (e.g., Halocynthia aurantium), crustaceans (e.g., Homarus americanus), Chelicerates (e.g., Tachypleus tridentatu), and mollusks (e.g., Mytilus edulis) have become a novel source for a number of AMPs [14]. Very recently, Nikapitiya et al. [15] synthesized an AMP named Octominin, which is based on the defense protein of Octopus minor; it showed an antifungal activity against Candida albicans. Moreover, a recent study showed that Octominin had an inhibitory effect on lipopolysaccharide (LPS)-induced chemokine and pro-inflammatory cytokine secretion [16]. Since Octominin contained the basic characteristics of AMPs, in this study, we tested its antibacterial activity against S. parauberis. Initially, we tested the antibiotic susceptibility of S. parauberis, antimicrobial activity of Octominin, and Octominin's possible modes of action, including morphological and structural alterations, membrane permeability changes, ROS generation, DNA binding capacity, anti-biofilm activity, and transcriptional changes of selected genes in S. parauberis. Finally, efficiency of Octominin in controlling an S. parauberis infection was investigated by in vivo, using zebrafish larvae.
Section snippets
Determination of the antibiotic resistance profile of S. parauberis
S. parauberis (lab strain) was cultured using tryptic soy agar (TSA)/broth (TSB) (Becton, Dickinson and Company, USA) containing 2% sodium chloride, at 28 °C. To investigate antibiotic resistance, we selected 19 different antibiotics belonging to 13 antibiotic classes, and performed the disc diffusion assay, according to the method described by Nikapitiya et al. [17]. Briefly, S. parauberis was spread by swabbing on TSA plates, and antibiotic discs (6 mm) (BD BBL™ Sensi-Disc™, Becton, Dickinson
Antibiotic resistance profile of S. parauberis
To detect the possible drug resistance of S. parauberis, antibiotic susceptibility tests were conducted using 19 antibiotics. It was shown that S. parauberis has developed resistance for 11 (57.8%) selected antibiotics including streptomycin, gentamycin, amikacin, tetracycline, vancomycin, erythromycin, tobramycin, penicillin, ampicillin, clindamycin, and sulfamethoxazole/trimethoprim (Table 2). Among them, four antibiotics (streptomycin, erythromycin, penicillin, and ampicillin) had the
Discussion
AMPs are successful alternatives to antibiotics, and provide a promising solution for controlling MDR pathogens, by disturbing their multiple physiologic and metabolic processes. However, resistance development for some AMPs has been reported recently [7]. Gram-positive bacteria are coated with an acidic polymer of teichoic acid associated with a peptidoglycan layer, which forms a net negative charge on the outer surface. In addition, it acts as a major defense against environmental threats [23
CRediT authorship contribution statement
E.H.T. Thulshan Jayathilaka: Methodology, Investigation, Formal analysis, Writing - original draft, Writing - review & editing. T.D. Liyanage: Investigation, Formal analysis, Writing - review & editing. D.C. Rajapaksha: Methodology, Investigation, Formal analysis, Writing - review & editing. S.H.S. Dananjaya: Investigation, Formal analysis. Chamilani Nikapitiya: Methodology, Supervision, Writing - review & editing. Ilson Whang: Conceptualization, Funding acquisition, Project administration,
Declaration of competing interest
The authors declared that no conflicts of interest.
Acknowledgments
This work was supported by the Research Program of the National Marine Biodiversity Institute of Korea (MABIK2021M00600), funded by the Ministry of Oceans and Fisheries, and the National Research Foundation of Korea (NRF) grants, funded by the Korean government (MSIT) (2019R1A2C1087028 and 2018R1A2B6007841).
References (53)
- et al.
Antimicrobial peptides
Curr. Biol.
(2016) - et al.
The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis
Biochim. Biophys. Acta Gen. Subj.
(2011) - et al.
Understanding bacterial resistance to antimicrobial peptides: from the surface to deep inside
Biochim. Biophys. Acta Biomembr.
(2015) - et al.
Current challenges of Streptococcus infection and effective molecular, cellular, and environmental control methods in aquaculture
Mol. Cell.
(2018) - et al.
Antibiotic susceptibility and resistance of Streptococcus iniae and Streptococcus parauberis isolated from olive flounder (Paralichthys olivaceus)
Vet. Microbiol.
(2009) - et al.
Antimicrobial proline-rich peptides from the hemolymph of marine snail Rapana venosa
Peptides
(2011) - et al.
Analysis of relative gene expression data using Real-Time Quantitative PCR and the 2-ΔΔCT method
Methods
(2001) - et al.
Novel pectin isolated from Spirulina maxima enhances the disease resistance and immune responses in zebrafish against Edwardsiella piscicida and Aeromonas hydrophila
Fish Shellfish Immunol.
(2019) - et al.
Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens
Biochim. Biophys. Acta Biomembr.
(2015) - et al.
SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides
J. Biol. Chem.
(2003)
Two short antimicrobial peptides derived from prosaposin-like proteins in the starry flounder (Platichthys stellatus)
Fish Shellfish Immunol.
Effect of a novel antimicrobial peptide chrysophsin-1 on oral pathogens and Streptococcus mutans biofilms
Peptides
Phospholipid-driven differences determine the action of the synthetic antimicrobial peptide OP-145 on Gram-positive bacterial and mammalian membrane model systems
Biochim. Biophys. Acta Biomembr.
Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: complex interplay of electrostatic and hydrophobic interactions
Biochim. Biophys. Acta Biomembr.
Mechanism of action of puroindoline derived tryptophan-rich antimicrobial peptides
Biochim. Biophys. Acta Biomembr.
Effective antimicrobial activity of Cbf-14, derived from a cathelin-like domain, against penicillin-resistant bacteria
Biomaterials
Antimicrobial and DNA-binding activities of the peptide fragments of human lactoferrin and histatin 5 against Streptococcus mutans
Arch. Oral Biol.
Biofilms in water, its role and impact in human disease transmission
Curr. Opin. Biotechnol.
Mechanisms of antibiotic resistance in bacterial biofilms
Int. J. Med. Microbiol.
Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies
J. Biotechnol.
Mechanisms of biofilm resistance to antimicrobial agents
Trends Microbiol.
The role of CDP-diacylglycerol synthetase and phosphatidylinositol synthase activity levels in the regulation of cellular phosphatidylinositol content
J. Biol. Chem.
AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense
Trends Immunol.
Mechanisms of action for antimicrobial peptides with antibacterial and antibiofilm functions
Front. Microbiol.
Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance
Nat. Commun.
Characterization of antimicrobial peptides toward the development of novel antibiotics
Pharmaceuticals
Cited by (13)
Octominin: An antimicrobial peptide with antibacterial and anti-inflammatory activity against carbapenem-resistant Escherichia coli both in vitro and in vivo
2023, Journal of Global Antimicrobial ResistanceIn-vitro immunomodulatory responses and antiviral activities of antimicrobial peptide octominin against fish pathogenic viruses
2023, Fish and Shellfish ImmunologyOctopromycin: Antibacterial and antibiofilm functions of a novel peptide derived from Octopus minor against multidrug-resistant Acinetobacter baumannii
2021, Fish and Shellfish ImmunologyCitation Excerpt :Recently, Maselli et al. [6] reported the effects of a novel AMP (OctoPartenopin), extracted from the suckers of O. vulgaris, against, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Additionally, we demonstrated a novel synthetic peptide ‘Octominin’ designed on the basis of defense protein 3 of O. minor; it exhibited anticandidal [7] and antibacterial activities [8,9]. Multidrug-resistant (MDR) ESKAPE bacteria (Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa, and Enterobacter sp.) have emerged as the leading causes of nosocomial infections [10].
The antibacterial activity and mechanism of a novel peptide MR-22 against multidrug-resistant Escherichia coli
2024, Frontiers in Cellular and Infection MicrobiologyAntifungal Efficacy of Antimicrobial Peptide Octominin II against Candida albicans
2023, International Journal of Molecular Sciences