Antibacterial Activity of Rationally Designed Antimicrobial Peptides

Many infectious diseases are still prevalent in the world’s populations since no effective treatments are available to eradicate them. The reasons may either be the antibiotic resistance towards the available therapeutic molecules or the slow rate of producing adequate therapeutic regimens to tackle the rapid growth of new infectious diseases, as well as the toxicity of current treatment regimens. Due to these reasons, there is a need to seek and develop novel therapeutic regimens to reduce the rapid scale of bacterial infections. Antimicrobial Peptides (AMPs) are components of the first line of defense for prokaryotes and eukaryotes and have a wide range of activities against Gram-negative and Gram-positive bacteria, fungi, cancer cells, and protozoa, as well as viruses. In this study, peptides which were initially identified for their HIV inhibitory activity were further screened for antibacterial activity through determination of their kinetics as well as their cytotoxicity. From the results obtained, the MICs of two AMPs (Molecule 3 and Molecule 7) were 12.5 μg/ml for K. pneumoniae (ATCC 700603) and 6.25 μg/ml for P. aeruginosa (ATCC 22108). The two AMPs killed these bacteria rapidly in vitro, preventing bacterial growth within few hours of treatment. Furthermore, the cytotoxic activity of these two peptides was significantly low, even at an AMP concentration of 100 μg/ml. These results revealed that Molecule 3 and 7 have great potential as antibacterial drugs or could serve as lead compounds in the design of therapeutic regimens for the treatment of antibiotic-resistant bacteria.

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Aptamers in the Treatment of Bacterial Infections: Problems and Prospects

Annals of the Russian academy of medical sciences ◽

10.15690/vramn591 ◽

2016 ◽

Vol 71 (5) ◽

pp. 350-358

Author(s):

N. A. Zeninskaya ◽

A. V. Kolesnikov ◽

A. K. Ryabko ◽

I. G. Shemyakin ◽

I. A. Dyatlov ◽

...

Keyword(s):

Drug Discovery ◽

High Throughput Screening ◽

Bacterial Infections ◽

Point Of View ◽

Aptamer Selection ◽

Wide Range ◽

Therapeutic Molecules ◽

Molecular Selection ◽

The Stability

Aptamers are short single-stranded oligonucleotides which are selected via targeted chemical evolution in vitro to bind a molecular target of interest. The aptamer selection technology is designated as SELEX (Systematic evolution of ligands by exponential enrichment). SELEX enables isolation of oligonucleotide aptamers binding a wide range of targets of interest with little respect for their nature and molecular weight. A number of applications of aptamer selection were developed ranging from biosensor technologies to antitumor drug discovery. First aptamer-based pharmaceutical (Macugen) was approved by FDA for clinical use in 2004, and since then more than ten aptamer-based drugs undergo various phases of clinical trials. From the medicinal chemist’s point of view, aptamers represent a new class of molecules suitable for the development of new therapeutics. Due to the stability, relative synthesis simplicity, and development of advanced strategies of target specific molecular selection, aptamers attract increased attention of drug discovery community. Difficulties of the development of next-generation antibiotics basing on the conventional basis of combinatorial chemistry and high-throughput screening have also amplified the interest to aptamer-based therapeutic candidates. The present article reviews the investigations focused on the development of antibacterial aptamers and discusses the potential and current limitations of the use of this type of therapeutic molecules.

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Staphylococcal-Produced Bacteriocins and Antimicrobial Peptides: Their Potential as Alternative Treatments for Staphylococcus aureus Infections

Antibiotics ◽

10.3390/antibiotics9020040 ◽

2020 ◽

Vol 9 (2) ◽

pp. 40 ◽

Cited By ~ 6

Author(s):

Logan L. Newstead ◽

Katarina Varjonen ◽

Tim Nuttall ◽

Gavin K. Paterson

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Peptides ◽

Genome Mining ◽

Resistant Bacteria ◽

Coagulase Negative Staphylococci ◽

Novel Treatments ◽

Wide Range ◽

Almost All

Staphylococcus aureus is an important pathogen of both humans and animals, implicated in a wide range of infections. The emergence of antibiotic resistance has resulted in S. aureus strains that are resistant to almost all available antibiotics, making treatment a clinical challenge. Development of novel antimicrobial approaches is now a priority worldwide. Bacteria produce a range of antimicrobial peptides; the most diverse of these being bacteriocins. Bacteriocins are ribosomally synthesised peptides, displaying potent antimicrobial activity usually against bacteria phylogenetically related to the producer strain. Several bacteriocins have been isolated from commensal coagulase-negative staphylococci, many of which display inhibitory activity against S. aureus in vitro and in vivo. The ability of these bacteriocins to target biofilm formation and their novel mechanisms of action with efficacy against antibiotic-resistant bacteria make them strong candidates as novel therapeutic antimicrobials. The use of genome-mining tools will help to advance identification and classification of bacteriocins. This review discusses the staphylococcal-derived antimicrobial peptides displaying promise as novel treatments for S. aureus infections.

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Antibacterial Potential of Biosynthesized Zinc Oxide Nanoparticles against Poultry-Associated Foodborne Pathogens: An In Vitro Study

Animals ◽

10.3390/ani11072093 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2093

Author(s):

Hidayat Mohd Yusof ◽

Nor’Aini Abdul Rahman ◽

Rosfarizan Mohamad ◽

Uswatun Hasanah Zaidan ◽

Anjas Asmara Samsudin

Keyword(s):

Zinc Oxide ◽

Antibacterial Activity ◽

Foodborne Pathogens ◽

Zinc Oxide Nanoparticles ◽

Resistant Bacteria ◽

Oxide Nanoparticles ◽

Zno Nps ◽

Wide Range ◽

Antibacterial Potential

Since the emergence of multidrug-resistant bacteria in the poultry industry is currently a serious threat, there is an urgent need to develop a more efficient and alternative antibacterial substance. Zinc oxide nanoparticles (ZnO NPs) have exhibited antibacterial efficacy against a wide range of microorganisms. Although the in vitro antibacterial activity of ZnO NPs has been studied, little is known about the antibacterial mechanisms of ZnO NPs against poultry-associated foodborne pathogens. In the present study, ZnO NPs were successfully synthesized using Lactobacillus plantarum TA4, characterized, and their antibacterial potential against common avian pathogens (Salmonella spp., Escherichia coli, and Staphylococcus aureus) was investigated. Confirmation of ZnO NPs by UV-Visual spectroscopy showed an absorption band center at 360 nm. Morphologically, the synthesized ZnO NPs were oval with an average particle size of 29.7 nm. Based on the dissolution study of Zn2+, ZnO NPs released more ions than their bulk counterparts. Results from the agar well diffusion assay indicated that ZnO NPs effectively inhibited the growth of the three poultry-associated foodborne pathogens. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were assessed using various concentrations of ZnO NPs, which resulted in excellent antibacterial activity as compared to their bulkier counterparts. S. aureus was more susceptible to ZnO NPs compared to the other tested bacteria. Furthermore, the ZnO NPs demonstrated substantial biofilm inhibition and eradication. The formation of reactive oxygen species (ROS) and cellular material leakage was quantified to determine the underlying antibacterial mechanisms, whereas a scanning electron microscope (SEM) was used to examine the morphological changes of tested bacteria treated with ZnO NPs. The findings suggested that ROS-induced oxidative stress caused membrane damage and bacterial cell death. Overall, the results demonstrated that ZnO NPs could be developed as an alternative antibiotic in poultry production and revealed new possibilities in combating pathogenic microorganisms.

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Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽

10.3390/molecules26072047 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2047

Author(s):

Magda Ferreira ◽

Maria Ogren ◽

Joana N. R. Dias ◽

Marta Silva ◽

Solange Gil ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

Private Investment ◽

Therapeutic Index ◽

Multidrug Resistant ◽

Current Treatment ◽

Delivery Systems ◽

Resistant Bacteria ◽

Bacterial Cells ◽

Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

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The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

International Journal of Molecular Sciences ◽

10.3390/ijms22063253 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3253

Author(s):

Clarisse Roblin ◽

Steve Chiumento ◽

Cédric Jacqueline ◽

Eric Pinloche ◽

Cendrine Nicoletti ◽

...

Keyword(s):

Antibacterial Activity ◽

Human Health ◽

Biological Activities ◽

Resistant Bacteria ◽

Modified Peptides ◽

The 1960S ◽

Conventional Antibiotics ◽

Clinical Potential

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.

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Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Hetero-Complex Formation

Molecules ◽

10.3390/molecules26123628 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3628

Author(s):

Anna Woziwodzka ◽

Marta Krychowiak-Maśnicka ◽

Grzegorz Gołuński ◽

Anna Felberg ◽

Agnieszka Borowik ◽

...

Keyword(s):

Antibacterial Activity ◽

Drug Repurposing ◽

Activity Level ◽

Titration Calorimetry ◽

Human Pathogens ◽

Neighborhood Association ◽

Treatment Regimens ◽

Vis Spectroscopy ◽

Antibiotic Interactions

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8–45.6 M−1 and enthalpy change values up to −4 kJ·M−1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.

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Assessment of Microbial Load of Un-pasteurized Fruit Juices and in vitro Antibacterial Potential of Honey Against Bacterial Isolates

The Open Microbiology Journal ◽

10.2174/1874285801509010026 ◽

2015 ◽

Vol 9 (1) ◽

pp. 26-32 ◽

Cited By ~ 4

Author(s):

Muhammad Naeem Iqbal ◽

Aftab Ahmad Anjum ◽

Muhammad Asad Ali ◽

Firasat Hussain ◽

Shahzad Ali ◽

...

Keyword(s):

Antibacterial Activity ◽

Viable Count ◽

Fruit Juices ◽

Microbial Load ◽

Resistant Bacteria ◽

Klebsiella Pneumonia ◽

Street Vendors ◽

Permissible Limits ◽

Development Of Resistance

The development of resistance in bacteria against commonly used antibiotics/drugs is of considerable medical significance. Aim of this study was to determine the microbial load of un-pasteurized packed fruit juices sold in Lahore city and to determine antibacterial activity of five different honey samples against isolated bacteria. Unpasteurized fruit juice samples (n=60) were collected from street vendors. All the samples were subjected to Total viable count (TVC), Staphylococcal count (SC) and Coliform count (CC). One hundred and ten strains of bacteria were isolated from various fruit juices and identified on the basis of cultural characters, morphology and biochemical characters. Mean TVCs, SCs and CCs of juices (6.80±1.91, 5.45±1.06 and 3.25±1.25 log10 CFU/ml respectively) were non-significant with standard permissible limits (p<0.05). Among all the fruit juices, 66.66% of samples had TVC more than 4 log10 CFU/ml, 51.66% of samples had SC more than 3 log10 CFU/ml and 46.66% of samples had CC more than 2 log10 CFU/ml. Among the bacillus isolates purified, were Bacillus alvei, Bacillus subtilis, Bacillus polymyxa, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli and Enterobecter. All five different types of honey samples used in this study showed antibacterial activity against B. alvei, B. polymyxa, B. subtilis and S. aureus and no activity against P. aeruginosa, K. pneumonia, Enterobecter and E. coli. It is concluded that microbial load in unpasteurized fruit juices is significantly higher than standard permissible limits which insinuates its possible role in spoilage and food borne illnesses. Periodic monitoring of packed fruit juices should be carried out to make them safe for consumption. Honey can be used as an alternative for treatment of various infections, especially those caused by antibiotic resistant bacteria.

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In vitro evaluation of the probiotic potential of Lactobacillus isolated from native swine manure

Veterinary World ◽

10.14202/vetworld.2021.1133-1142 ◽

2021 ◽

pp. 1133-1142

Author(s):

Chiraprapha Tuyarum ◽

Aporn Songsang ◽

Monthon Lertworapreecha

Keyword(s):

Antibacterial Activity ◽

Initial Conditions ◽

Swine Manure ◽

Enterohemorrhagic Escherichia Coli ◽

Feed Additive ◽

Pig Manure ◽

Resistant Bacteria ◽

Attractive Alternative ◽

Probiotic Properties

Background and Aim: Using antimicrobials as a feed additive in swine production is prohibited because it is a major cause of the emergence of antimicrobial-resistant bacteria. Probiotics such as Lactobacillus spp. are an attractive alternative to reduce antimicrobial resistance and promote swine growth. This study aimed to evaluate the in vitro probiotic properties of Lactobacillus isolated from indigenous swine manure. Materials and Methods: A total of 30 fecal samples from healthy individual indigenous pigs were collected and isolated on de Man, Rogosa, and Sharpe agar. The preliminary screen identified candidates with antibacterial activity against six pathogens and >50% survival and tolerance to acid (pH 3.0) and 1% bile salt. Isolates that passed the initial screen will be tested for other probiotic properties. Results: Of the 314 isolates from 30 pig manure samples, 17 isolates satisfied all initial conditions for probiotic properties. Each isolate has unique, distinctive properties. Isolates B4, B5, B8, B17, B87, and B144 formed thick biofilms, whereas isolates B5, B8, and 27 adhered well to the intestinal wall and exhibited strong autoaggregation properties. Isolate B4 aggregated with Enterohemorrhagic Escherichia coli and Enteropathogenic E. coli. Tests in pH-adjusted cell-free medium indicated that the antibacterial activity resulted from bacterial acidification rather than bacteriocin formation. Sequence analysis (16S rRNA) revealed 16 of the isolates were Lactobacillus plantarum, and only one isolate was Lactobacillus salivarius. Conclusion: We isolated 17 Lactobacillus from swine manure and demonstrated that their probiotic properties might be useful as a probiotic cocktail for swine feed.

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Antimicrobial Peptides Epinecidin-1 and Beta-Defesin-3 Are Effective against a Broad Spectrum of Antibiotic-Resistant Bacterial Isolates and Increase Survival Rate in Experimental Sepsis

Antibiotics ◽

10.3390/antibiotics11010076 ◽

2022 ◽

Vol 11 (1) ◽

pp. 76

Author(s):

Albert Bolatchiev

Keyword(s):

Antibacterial Activity ◽

Survival Rate ◽

Antimicrobial Peptides ◽

Lethal Dose ◽

Experimental Models ◽

Experimental Sepsis ◽

Epinephelus Coioides ◽

Sterile Saline

The antimicrobial peptides human Beta-defensin-3 (hBD-3) and Epinecidin-1 (Epi-1; by Epinephelus coioides) could be a promising tool to develop novel antibacterials to combat antibiotic resistance. The antibacterial activity of Epi-1 + vancomycin against methicillin-resistant Staphylococcus aureus (22 isolates) and Epi-1 + hBD-3 against carbapenem-resistant isolates of Klebsiella pneumoniae (n = 23), Klebsiella aerogenes (n = 17), Acinetobacter baumannii (n = 9), and Pseudomonas aeruginosa (n = 13) was studied in vitro. To evaluate the in vivo efficacy of hBD-3 and Epi-1, ICR (CD-1) mice were injected intraperitoneally with a lethal dose of K. pneumoniae or P. aeruginosa. The animals received a single injection of either sterile saline, hBD-3 monotherapy, meropenem monotherapy, hBD-3 + meropenem, or hBD-3 + Epi-1. Studied peptides showed antibacterial activity in vitro against all studied clinical isolates in a concentration of 2 to 32 mg/L. In both experimental models of murine sepsis, an increase in survival rate was seen with hBD-3 monotherapy, hBD-3 + meropenem, and hBD-3 + Epi-1. For K. pneumoniae-sepsis, hBD-3 was shown to be a promising option in overcoming the resistance of Klebsiella spp. to carbapenems, though more research is needed. In the P. aeruginosa-sepsis model, the addition of Epi-1 to hBD-3 was found to have a slightly reduced mortality rate compared to hBD-3 monotherapy.

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Antibacterial Efficacy of Some Medicinal Plants on Multidrug Resistance Bacteria and Their Toxicity on Eukaryotic Cells

Applied Sciences ◽

10.3390/app11188479 ◽

2021 ◽

Vol 11 (18) ◽

pp. 8479

Author(s):

Sereen M. B. Bataineh ◽

Yaser H. Tarazi ◽

Wafá A. Ahmad

Keyword(s):

Multidrug Resistance ◽

Camellia Sinensis ◽

Plant Extracts ◽

Bacterial Infections ◽

Eukaryotic Cells ◽

Resistant Bacteria ◽

Thymus Vulgaris ◽

Significant Activity ◽

Medicinal Plant Extracts

The aim of this study was to evaluate the in vitro antimicrobial activity of medicinal Methanolic plant extracts against multidrug-resistant bacteria to determine the cytotoxicity of these extracts on eukaryotic cells, and to confirm their efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA) in experimental animals. The effects of the methanol extract of sixty folk plants were investigated on; MRSA, Extended Spectrum Beta-Lactamase E. coli and MDR Pseudomonas aeruginosa by disc diffusion and MIC assay. Cytotoxicity was determined using MTT and hemolysis of human erythrocytes. Three plant extracts with the highest antimicrobial activities were tested using a challenge experiment on mice. Systemic infection was performed by intraperitoneal inoculation of (5 × 106 CFU/mL) of MRSA isolate. Then mice received 300 mg/kg body weight of the plant extracts daily for seven days. The efficacy of plant extracts was evaluated by general health, mortality rate, gross lesion, and histopathology study of inoculated mice. Only ten plants showed activities against different MDR bacteria with inhibitory zones ranging from (8 to 22 mm) in diameter. Of the ten medicinal plant extracts, and Aloysia citrodora showed the highest activities against MRSA and Camellia sinensis MSSA isolates, with MIC values ranging from 0.5 to 1.5 mg/mL, followed by Hibiscus sabdariffa, Thymus vulgaris, and Glycyrrhiza glabra. Furthermore, the extract of the effective plants showed low toxicity against Vero and fibroblasts cell lines, along with inhibitory activities to erythrocytes membrane disruption. The in vivo study demonstrated that Camellia sinensis showed significant activity against MRSA infections in mice. The results validate that these plants are effective and safe antibacterial agents against multidrug-resistance bacteria, and have the potential to be utilized as an alternative to antibiotics for the treatment of bacterial infections.

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