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14 pages, 927 KiB

Open AccessArticle

Antimicrobial Activities of α-Helix and β-Sheet Peptides against the Major Bovine Respiratory Disease Agent, Mannheimia haemolytica

by Ruina Bao, Zhi Ma, Kim Stanford, Tim A. McAllister and Yan D. Niu

Int. J. Mol. Sci. 2024, 25(8), 4164; https://doi.org/10.3390/ijms25084164 - 09 Apr 2024

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Abstract

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in [...] Read more.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2 being the most efficacious against multiple isolates. At 8–16 µg/mL, WK2 was bactericidal against Mh 330 in broth, and at 32 µg/mL in the presence of BT cells, it reduced the population by 3 logs CFU/mL without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine) and ONPG (o-Nitrophenyl β-D-galactopyranoside), with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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12 pages, 1651 KiB

Open AccessArticle

Absence of Synergism between a Dual-AMP Biogel and Antibiotics Used as Therapeutic Agents for Diabetic Foot Infections

by Rui Silva Soares, Diana Gomes, Isa Serrano, Eva Cunha, Luís Tavares and Manuela Oliveira

Int. J. Mol. Sci. 2024, 25(1), 407; https://doi.org/10.3390/ijms25010407 - 28 Dec 2023

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Abstract

Diabetic foot infections (DFIs) are frequently linked to diabetic-related morbidity and death because of the ineffectiveness of conventional antibiotics against multidrug-resistant bacteria. Pexiganan and nisin A are antimicrobial peptides (AMPs), and their application may complement conventional antibiotics in DFI treatment. A collagen 3D [...] Read more.

Diabetic foot infections (DFIs) are frequently linked to diabetic-related morbidity and death because of the ineffectiveness of conventional antibiotics against multidrug-resistant bacteria. Pexiganan and nisin A are antimicrobial peptides (AMPs), and their application may complement conventional antibiotics in DFI treatment. A collagen 3D model, previously established to mimic a soft-tissue collagen matrix, was used to evaluate the antibacterial efficacy of a guar gum gel containing pexiganan and nisin alone and combined with three antimicrobials toward the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa isolated from infected foot ulcers. Antimicrobials and bacterial diffusion were confirmed by spot-on-lawn and bacterial growth by bacterial count (cfu/mL). Our main conclusion was that the dual-AMP biogel combined with gentamicin, clindamycin, or vancomycin was not able to significantly reduce bacterial growth or eradicate S. aureus and P. aeruginosa DFI isolates. We further reported an antagonism between dual-AMP and dual-AMP combined with antibiotics against S. aureus. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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17 pages, 4989 KiB

Open AccessArticle

Searching for Virulence Factors among Staphylococcus lugdunensis Isolates from Orthopedic Infections: Correlation of β-hemolysin, hemolysin III, and slush Genes with Hemolytic Activity and Synergistic Hemolytic Activity

by Stefano Ravaioli, Davide Campoccia, Rasoul Mirzaei, Valentina Mariani, Giulia Bottau, Andrea De Donno, Lucio Montanaro, Pietro Speziale and Carla Renata Arciola

Int. J. Mol. Sci. 2023, 24(21), 15724; https://doi.org/10.3390/ijms242115724 - 29 Oct 2023

Cited by 1 | Viewed by 819

Abstract

Staphylococcus lugdunensis is an emerging high-virulent pathogen. Here, the presence and expression of virulence genes (icaA, fbl, vwbl, fbpA, slush A, B and C, and genes of the putative β-hemolysin and hemolysin III) and the [...] Read more.

Staphylococcus lugdunensis is an emerging high-virulent pathogen. Here, the presence and expression of virulence genes (icaA, fbl, vwbl, fbpA, slush A, B and C, and genes of the putative β-hemolysin and hemolysin III) and the ability to induce synergistic hemolytic activity and hemolysis after 24, 48 and 72 h were investigated in a collection of twenty-two S. lugdunensis clinical isolates. The collection of isolates, mainly from implant orthopedic infections, had previously been grouped by ribotyping/dendrogram analysis and studied for biofilm matrices, biomasses and antibiotic resistances. Two isolates, constituting a unique small ribogroup sharing the same cluster, exhibited an amplicon size of the slush operon (S. lugdunensis synergistic hemolysin) which was shorter than the expected 977 bp. This outcome can predict the genetic lineage of the S. lugdunensis strains. One isolate (cra1342) presented two deletions: one of 90 bp in slush A and the other of 91 bp in slush B. Another isolate (N860314) showed a single 193 bp deletion, which encompassed part of the slush B terminal sequence and most of slush C. The isolate N860314 was devoid of hemolytic activity after 24 h, and the first consideration was that the deleted region deals with the coding of the active enzymatic site of the slush hemolysin. On the other hand, cra1342 and N860314 isolates with different slush deletions and with hemolytic activity after 24 and 48 h, respectively, could have replaced the hemolytic phenotype through other processes. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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21 pages, 4311 KiB

Open AccessArticle

A Designed Analog of an Antimicrobial Peptide, Crabrolin, Exhibits Enhanced Anti-Proliferative and In Vivo Antimicrobial Activity

by Aifang Yao, Yingxue Ma, Ruize Sun, Wanchen Zou, Xiaoling Chen, Mei Zhou, Chengbang Ma, Tianbao Chen, Chris Shaw and Lei Wang

Int. J. Mol. Sci. 2023, 24(19), 14472; https://doi.org/10.3390/ijms241914472 - 23 Sep 2023

Cited by 1 | Viewed by 1107

Abstract

Antimicrobial peptides have gradually attracted interest as promising alternatives to conventional agents to control the worldwide health threats posed by antibiotic resistance and cancer. Crabrolin is a tridecapeptide extracted from the venom of the European hornet (Vespa crabro). Its antibacterial and [...] Read more.

Antimicrobial peptides have gradually attracted interest as promising alternatives to conventional agents to control the worldwide health threats posed by antibiotic resistance and cancer. Crabrolin is a tridecapeptide extracted from the venom of the European hornet (Vespa crabro). Its antibacterial and anticancer potentials have been underrated compared to other peptides discovered from natural resources. Herein, a series of analogs were designed based on the template sequence of crabrolin to study its structure–activity relationship and enhance the drug’s potential by changing the number, type, and distribution of charged residues. The cationicity-enhanced derivatives were shown to have improved antibacterial and anticancer activities with a lower toxicity. Notably, the double-arginine-modified product, crabrolin-TR, possessed a potent capacity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 4 μM), which was around thirty times stronger than the parent peptide (MIC = 128 μM). Furthermore, crabrolin-TR showed an in vivo treatment efficacy in a Klebsiella-pneumoniae-infected waxworm model and was non-toxic under its maximum MBC value (MIC = 8 μM), indicating its therapeutic potency and better selectivity. Overall, we rationally designed functional peptides by progressively increasing the number and distribution of charged residues, demonstrating new insights for developing therapeutic molecules from natural resources with enhanced properties, and proposed crabrolin-TR as an appealing antibacterial and anticancer agent candidate for development. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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19 pages, 5050 KiB

Open AccessArticle

Antifungal Efficacy of Antimicrobial Peptide Octominin II against Candida albicans

by J. N. C. Jayasinghe, Ilson Whang and Mahanama De Zoysa

Int. J. Mol. Sci. 2023, 24(18), 14053; https://doi.org/10.3390/ijms241814053 - 13 Sep 2023

Cited by 3 | Viewed by 1125

Abstract

Most clinically isolated Candida albicans strains are drug-resistant, emphasizing the urgent need to discover alternative therapies. In this study, the previously characterized Octominin was modified into a shorter peptide with an 18 amino acid sequence (¹GWLIRGAIHAGKAIHGLI¹⁸) and named Octominin [...] Read more.

Most clinically isolated Candida albicans strains are drug-resistant, emphasizing the urgent need to discover alternative therapies. In this study, the previously characterized Octominin was modified into a shorter peptide with an 18 amino acid sequence (¹GWLIRGAIHAGKAIHGLI¹⁸) and named Octominin II. The secondary structure of Octominin II is a random coil with a helical turn and a positive charge (+2.46) with a hydrophobic ratio of 0.46. Octominin II inhibited C. albicans, C. auris, and C. glabrata with minimum inhibitory and fungicidal concentrations against C. albicans of 80 and 120 µg/mL, respectively. Field emission scanning electron microscopy confirmed that Octominin II treatment caused ultra-structural changes in C. albicans cells. Furthermore, membrane permeability results for the fluorescent indicator propidium iodide revealed modifications in cell wall integrity in Octominin II-treated C. albicans. Octominin II treatment increases the production of reactive oxygen species (ROS) in C. albicans. Gene expression studies revealed that Octominin II suppresses virulence genes of C. albicans such as CDR1, TUP1, AGE3, GSC1, SAP2, and SAP9. In addition, a nucleic acid binding assay revealed that Octominin II degraded genomic DNA and total RNA in a concentration-dependent manner. Additionally, Octominin II inhibited and eradicated C. albicans biofilm formation. Octominin II showed relatively less cytotoxicity on raw 264.7 cells (0–200 µg/mL) and hemolysis activity on murine erythrocytes (6.25–100 µg/mL). In vivo studies confirmed that Octominin II reduced the pathogenicity of C. albicans. Overall, the data suggests that Octominin II inhibits C. albicans by employing different modes of action and can be a promising candidate for controlling multidrug-resistant Candida infections. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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25 pages, 3346 KiB

Open AccessArticle

Fighting Pseudomonas aeruginosa Infections: Antibacterial and Antibiofilm Activity of D-Q53 CecB, a Synthetic Analog of a Silkworm Natural Cecropin B Variant

by Irene Varponi, Stefania Ferro, Luca Menilli, Alessandro Grapputo, Francesca Moret, Francesca Mastrotto, Oriano Marin and Federica Sandrelli

Int. J. Mol. Sci. 2023, 24(15), 12496; https://doi.org/10.3390/ijms241512496 - 06 Aug 2023

Cited by 2 | Viewed by 1224

Abstract

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium responsible for severe nosocomial infections and is considered a critical pulmonary pathogen for both immunocompromised and cystic fibrosis patients. Planktonic cells of P. aeruginosa possess intrinsic and acquired resistances, inactivating several classes of conventional antibiotics. Additionally, [...] Read more.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium responsible for severe nosocomial infections and is considered a critical pulmonary pathogen for both immunocompromised and cystic fibrosis patients. Planktonic cells of P. aeruginosa possess intrinsic and acquired resistances, inactivating several classes of conventional antibiotics. Additionally, this bacterium can grow, forming biofilms, and complex structures, further hampering the action of multiple antibiotics. Here, we report the biological properties of D-Q53 CecB, an all-D enantiomer of the silkworm natural peptide Q53 CecB. Compared to the L-variant, D-Q53 CecB was resistant to in vitro degradation by humans and P. aeruginosa elastases and showed an enhanced bactericidal activity against P. aeruginosa planktonic bacteria. D-Q53 CecB was thermostable and maintained its antimicrobial activity at high salt concentrations and in the presence of divalent cations or fetal-bovine serum, although at reduced levels. Against different types of human cells, D-Q53 CecB showed cytotoxic phenomena at concentrations several folds higher compared to those active against P. aeruginosa. When L- and D-Q53 CecB were compared for their antibiofilm properties, both peptides were active in inhibiting biofilm formation. However, the D-enantiomer was extremely effective in inducing biofilm degradation, suggesting this peptide as a favorable candidate in an anti-Pseudomonas therapy. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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12 pages, 1130 KiB

Open AccessArticle

Antibacterial Activity on Orthopedic Clinical Isolates and Cytotoxicity of the Antimicrobial Peptide Dadapin-1

by Davide Campoccia, Lucio Montanaro, Stefano Ravaioli, Valentina Mariani, Giulia Bottau, Andrea De Donno and Carla Renata Arciola

Int. J. Mol. Sci. 2023, 24(1), 779; https://doi.org/10.3390/ijms24010779 - 02 Jan 2023

Cited by 6 | Viewed by 2107

Abstract

In orthopedic surgery, biomaterial-associated infections represent a complication of serious concern. Most promising strategies to prevent these infections currently rely on the use of anti-infective biomaterials. Desirably, in anti-infective biomaterials, the antibacterial properties should be achieved by doping, grafting, or coating the material [...] Read more.

In orthopedic surgery, biomaterial-associated infections represent a complication of serious concern. Most promising strategies to prevent these infections currently rely on the use of anti-infective biomaterials. Desirably, in anti-infective biomaterials, the antibacterial properties should be achieved by doping, grafting, or coating the material surfaces with molecules that are alternative to conventional antibiotics and exhibit a potent and highly specific activity against bacteria, without altering the biocompatibility. Antimicrobial peptides (AMPs) are among the most interesting candidate molecules for this biomaterial functionalization. Here, the potential expressed by the recently discovered peptide Dadapin-1 was explored by assaying its MIC, MBIC and MBC on clinical strains of relevant bacterial species isolated from orthopedic infections and by assessing its cytotoxicity on the human osteoblast-like MG63 cells. When appropriately tested in diluted Mueller Hinton Broth II (MHB II), Dadapin-1 exhibited significant antibacterial properties. MIC values were in the range of 3.1–6.2 µM for the gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus warneri, and 12.4–24.9 µM for the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Interestingly, the peptide was found non-cytotoxic, with an IC50 exceeding the highest concentration tested of 179 µM. Overall, Dadapin-1 expresses considerable potential for future application in the production of anti-infective biomaterials. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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Review

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22 pages, 1228 KiB

Open AccessReview

Recent Progress in the Characterization, Synthesis, Delivery Procedures, Treatment Strategies, and Precision of Antimicrobial Peptides

by Olalekan Olanrewaju Bakare, Arun Gokul, Lee-Ann Niekerk, Omolola Aina, Ademola Abiona, Adele Mariska Barker, Gerhard Basson, Mbukeni Nkomo, Laetitia Otomo, Marshall Keyster and Ashwil Klein

Int. J. Mol. Sci. 2023, 24(14), 11864; https://doi.org/10.3390/ijms241411864 - 24 Jul 2023

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Abstract

Infectious diseases are constantly evolving to bypass antibiotics or create resistance against them. There is a piercing alarm for the need to improve the design of new effective antimicrobial agents such as antimicrobial peptides which are less prone to resistance and possess high [...] Read more.

Infectious diseases are constantly evolving to bypass antibiotics or create resistance against them. There is a piercing alarm for the need to improve the design of new effective antimicrobial agents such as antimicrobial peptides which are less prone to resistance and possess high sensitivity. This would guard public health in combating and overcoming stubborn pathogens and mitigate incurable diseases; however, the emergence of antimicrobial peptides’ shortcomings ranging from untimely degradation by enzymes to difficulty in the design against specific targets is a major bottleneck in achieving these objectives. This review is aimed at highlighting the recent progress in antimicrobial peptide development in the area of nanotechnology-based delivery, selectivity indices, synthesis and characterization, their doping and coating, and the shortfall of these approaches. This review will raise awareness of antimicrobial peptides as prospective therapeutic agents in the medical and pharmaceutical industries, such as the sensitive treatment of diseases and their utilization. The knowledge from this development would guide the future design of these novel peptides and allow the development of highly specific, sensitive, and accurate antimicrobial peptides to initiate treatment regimens in patients to enable them to have accommodating lifestyles. Full article

(This article belongs to the Special Issue Recent Progress in Antimicrobial Peptides)

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