Antimicrobial peptides (AMPs) constitute a broad range of bioactive compounds in diverse organisms, including fish. They are effector molecules for the innate immune response, against pathogens, tissue damage and infections. Still, AMPs from African Catfish, Clarias gariepinus, skin mucus are largely unexplored despite their possible therapeutic role in combating antimicrobial resistance. In this study, African Catfish Antimicrobial peptides (ACAPs) were identified from the skin mucus of African Catfish, C. gariepinus. Native peptides were extracted from fish mucus scrapings in 10% acetic acid (v/v) and ultra-filtered using 5 kDa molecular weight cut-off membrane. The extract was purified using C₁₈ Solid-Phase Extraction. The antibacterial activity was determined using the Agar Well Diffusion method and broth-dilution method utilizing Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922). Thereafter, Sephadex G-25 gel filtration was further utilized in bio-guided isolation of the most active fractions prior to peptide identification using Orbitrap Fusion Lumos Tribrid Mass Spectrometry. The skin mucus extracted from African Catfish from all the three major lakes of Uganda exhibited antimicrobial activity on E. coli and S. aureus. Lake Albert’s C. gariepinus demonstrated the best activity with the lowest MIC of 2.84 and 0.71 μg/ml on S. aureus and E. coli, respectively. Sephadex G-25 peak I mass spectrometry analysis (Data are available via ProteomeXchange with identifier PXD029193) alongside in silico analysis revealed seven short peptides (11–16 amino acid residues) of high antimicrobial scores (0.561–0.905 units). In addition, these peptides had a low molecular weight (1005.57–1622.05 Da) and had percentage hydrophobicity above 54%. Up to four of these AMPs demonstrated α-helix structure conformation, rendering them amphipathic. The findings of this study indicate that novel AMPs can be sourced from the skin mucus of C. gariepinus. Such AMPs are potential alternatives to the traditional antibiotics and can be of great application to food and pharmaceutical industries; however, further studies are still needed to establish their drug-likeness and safety profiles.

Antimicrobial resistance remains a great threat to global health. In response to the World Health Organizations’ global call for action, nature has been explored for novel and safe antimicrobial candidates. To date, fish have gained recognition as potential source of safe, broad spectrum and effective antimicrobial therapeutics. The use of computational methods to design antimicrobial candidates of industrial application has however, been lagging behind. To fill the gap and contribute to the current fish-derived antimicrobial peptide repertoire, this study used Support Vector Machines algorithm to fish out fish-antimicrobial peptide-motif candidates encrypted in 127 peptides submitted at the Antimicrobial Peptide Database (APD3), steered by their physico-chemical characteristics (i.e., positive net charge, hydrophobicity, stability, molecular weight and sequence length). The best two novel antimicrobial peptide-motifs (A15_B, A15_E) with the lowest instability index (−28.25, −22.49, respectively) and highest isoelectric point (pI) index (10.48 for each) were selected for further analysis. Their 3D structures were predicted using I-TASSER and PEP-FOLD servers while ProSA, PROCHECK, and ANOLEA were used to validate them. The models predicted by I-TASSER were found to be better than those predicted by PEP-FOLD upon validation. Two I-TASSER models with the lowest c-score of −0.10 and −0.30 for A15_B and A15_E peptide-motifs, respectively, were selected for docking against known bacterial-antimicrobial target-proteins retrieved from protein databank (PDB). Carbapenam-3-carboxylate synthase (PDB ID; 4oj8) yielded the lowest docking energy (−8.80 and −7.80 Kcal/mol) against motif A15_B and A15_E, respectively, using AutoDock VINA. Further, in addition to Carbapenam-3-carboxylate synthase, these peptides (A15_B and A15_E) were found to as well bind to membrane protein (PDB ID: 1by3) and Carbapenem synthetase (PDB: 1q15) when ClusPro and HPEPDOCK tools were used. The membrane protein yielded docking energy scores (DES): −290.094, −270.751; coefficient weight (CW): −763.6, 763.3 for A15_B and A15_E) whereas, Carbapenem synthetase (PDB: 1q15) had a DES of −236.802, −262.75 and a CW of −819.7, −829.7 for peptides A15_B and A15_E, respectively. Motif A15_B of amino acid positions 2–19 in Pleurocidin exhibited the strongest in silico antimicrobial potentials. This segment could be a good biological candidate of great application in pharmaceutical industries as an antimicrobial drug candidate.

Amidst rising cases of antimicrobial resistance, antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics. Even so, poor pharmacokinetic profiles of certain AMPs impede their utility necessitating, a careful assessment of potential AMPs’ absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties during novel lead exploration. Accordingly, the present study utilized ADMET scores to profile seven previously isolated African catfish antimicrobial peptides (ACAPs). After profiling, the peptides were docked against approved bacterial protein targets to gain insight into their possible mode of action. Promising ACAPs were then chemically synthesized, and their antibacterial activity was validated in vitro utilizing the broth dilution method. All seven examined antimicrobial peptides passed the ADMET screening, with two (ACAP-IV and ACAP-V) exhibiting the best ADMET profile scores. The ACAP-V had a higher average binding energy (−8.47 kcal/mol) and average global energy (−70.78 kcal/mol) compared to ACAP-IV (−7.60 kcal/mol and −57.53 kcal/mol), with the potential to penetrate and disrupt bacterial cell membrane (PDB Id: 2w6d). Conversely, ACAP-IV peptide had higher antibacterial activity against E. coli and S. aureus (Minimum Inhibitory Concentration, 520.7 ± 104.3 μg/ml and 1666.7 ± 416.7 μg/ml, respectively) compared to ACAP-V. Collectively, the two antimicrobial peptides (ACAP-IV and ACAP-V) are potential novel leads for the food, cosmetic and pharmaceutical industries. Future research is recommended to optimize the expression of such peptides in biological systems for extended evaluation.

Antimicrobial resistance has posed a great global burden, with the fear that by 2050 it would have killed more people than cancer if nothing much is done about it. Alongside several attempts in place, zoo-therapy is becoming one of important remedies in the modern society, with hope for solution believed to be hidden in nature. In this study, the authors present a review of journal articles and reports obtained through key word search of several literature databases on recent developments in the battle against the antimicrobial resistance using fish derived antimicrobial peptides. The findings indicate despite some limitations of these antimicrobial peptides, their very broad spectrum activity against pathogens keeps them among promising antibiotics as far as the battle against multidrug resistance is concerned. Much as various methods to study antimicrobial peptides do exist, fish mucus remains less explored. The study recommends aquatic habitat exploration in search for novel bacterial antimicrobial peptides.

Aim: Medicinal plants have played an important role in the treatment of different ailments including malaria in developing countries particularly in Africa. This study has evaluated the antimalarial activities of Azadirachta indica A. Juss (Meliaceae), Cymbopogon citratus Stapf. (Poaceae), Moringa oleifera Lam. (Moringaceae), Tithonia diversifolia (Hemsl) A. Grey (Asteraceae) and Vernonia amygdalina Del. (Asteraceae) which are commonly-used for malaria treatment in Uganda. Study Design: This is an experimental laboratory report on antimalarial activities of some Ugandan medicinal plants for subsequent profiling in an herbal pharmacopoeia and eventual drug development. Place and Duration of Study: The Animal Research Facility and the Clinical and Research Laboratory, Faculty of Medicine, Mbarara University of Science and Technology, Uganda, between July 2019 and March 2020. Methodology: The antimalarial activity of the hot infusion of each leaf was evaluated on chloroquine-sensitive Plasmodium berghei ANKA-infected mice using 4-day test at 100 – 400 mg/kg with chloroquine (10 mg/kg) and artemether-lumefantrine (4 mg/kg) as positive controls; and distilled water as negative control. The observed haematological responses of the animals were determined with an automated haematometer. Results: The results showed dose-dependent activities in the animals treated with the extract of each plant leaf in varying degrees. Thus, V. amygdalina and T. diversifolia showed the highest antimalarial activities with the chemosuppression values of 75% and 66% at 400 mg/kg, respectively. The results of V. amygdalina, T. diversifolia and M. oleifera, extracts gave the lowest ED50 of 141, 195 and 231 mg/kg, respectively being significantly different from A. indica (ED50 319 mg/kg) and C. citratus (ED50 346 mg/kg) with V. amygdalina as the most potent extract among the five plant leaves. Conclusion: The observed activities of the five plants have therefore supported their folkloric uses as antimalarial remedies by the Ugandan traditional medicine practitioners with obvious potentials for drug development.