An Overview on Antimicrobial Potential of Edible Terrestrial Plants and Marine Macroalgae Rhodophyta and Chlorophyta Extracts.

Antibiotics are used to prevent and treat bacterial infections. After a prolonged use of antibiotics, it may happen that bacteria adapt to their presence, developing antibiotic resistance and bringing up health complications. Nowadays, antibiotic resistance is one of the biggest threats to global health and food security; therefore, scientists have been searching for new classes of antibiotic compounds which naturally express antimicrobial activity. In recent decades, research has been focused on the extraction of plant compounds to treat microbial infections. Plants are potential sources of biological compounds that express several biological functions beneficial for our organism, including antimicrobial activity. The high variety of compounds of natural origin makes it possible to have a great bioavailability of antibacterial molecules to prevent different infections. The antimicrobial activity of marine plants, also called seaweeds or macroalgae, for both Gram-positive and Gram-negative, and several other strains infective for humans, has been proven. The present review presents research focused on the extraction of antimicrobial compounds from red and green macroalgae (domain Eukarya, kingdom Plantae). Nevertheless, further research is needed to verify the action of macroalgae compounds against bacteria in vitro and in vivo, to be involved in the production of safe and novel antibiotics.

Bactericidal and antioxidant effects of essential oils from Satureja montana L., Myristica fragrans H. and Cymbopogon flexuosus.

The extraction and characterization of the essential oils (EO) from Satureja montana L., Myristica fragrans H. and Cymbopogon flexuosus and the determination of their antibacterial and antioxidant activities were achieved. The EO were identified by gas chromatography/mass spectrometry and quantified by gas chromatography using a flame ionization detector. The antibacterial potential against Escherichia coli and Staphylococcus aureus was evaluated by cell susceptibility assays and by scanning electron microscopy. The antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl assay, by ß-carotene bleaching and by determining the reducing power. Borneol (36·18%), γ-terpineol (12·66%) and carvacrol (11·07%) were the principal components in the EO from S. montana, and sabinene (49·23%) and α-pinene (13·81%) were found in the EO from M. fragrans. Geranial (59·66%) and neral (38·98%) isomers were the only major components in the EO from C. flexuosus. The EO from S. montana was effective against E. coli, with minimum inhibitory and bactericidal concentrations (MIC and MBC) of 6·25 µl ml-1 , whereas bactericidal potential against both was observed for the EO from M. fragrans; MIC = 6·25 µl ml-1 for S. aureus and MBC = 12·5 µl ml-1 for E. coli. A significant protective role on lipid substrates in the ß-carotene bleaching assay was seen for the EO from S. montana and M. fragrans. Overall, such EO can be promising agents against pathogenic bacteria and for protecting biomolecules during oxidative stress.

Antibacterial and antifungal activity of excretions and secretions of Calliphora vicina.

Antibiotic-resistant bacteria pose a major threat to global health in the 21st century, requiring a quick, cheap and effective response from public health officials. This study evaluated the antimicrobial activity of native excretions/secretions (NES) produced by third instar (3 days old) larvae of Calliphora vicina using a protocol adapted from the Institute of Clinical and Laboratory Standards (CLSI). The microorganisms tested were: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and the fungus Candida albicans. After the incubation period, the suspensions were diluted and spread on nutrient agar plates to count the colony-forming units. A turbidimetric test also was carried out to test the action of the NES of C. vicina against S. aureus, a very common bacterial species, with an enormous capacity for adaption and resistance, being one of the bacteria of medical importance that causes the most hospital and community infections in the world. According to our results, the NES of C. vicina exhibits antimicrobial activity at different dilutions, being most effective against the gram-negative bacteria E. coli and K. pneumoniae.

A Novel Antibiotic Mechanism of l-Cyclopropylalanine Blocking the Biosynthetic Pathway of Essential Amino Acid l-Leucine.

The unusual amino acid l-cyclopropylalanine was isolated from the mushroom Amanita virgineoides after detection in an anti-fungal screening test. l-Cyclopropylalanine was found to exhibit broad-spectrum inhibition against fungi and bacteria. The anti-fungal activity was found to be abolished in the presence of the amino acid l-leucine, but not any other amino acids, indicating that l-cyclopropylalanine may block the biosynthesis of the essential amino acid l-leucine, thereby inhibiting fungal and bacteria growth. Further biochemical studies found l-cyclopropylalanine indeed inhibits α-isopropylmalate synthase (α-IMPS), the enzyme that catalyzes the rate-limiting step in the biosynthetic pathway of l-leucine. Inhibition of essential l-leucine synthesis in fungal and bacteria organisms, a pathway absent in host organisms such as humans, may represent a novel antibiotic mechanism to counter the ever-increasing problem of drug resistance to existing antibiotics.

Untargeted metabolomics uncovers prime pathways linked to antibacterial action of citral against bacterial vaginosis-causing Gardnerella vaginalis: An in vitro and in vivo study.

Global increase in recurrence of bacterial vaginosis (BV) and worrisome rise in antimicrobial resistance pose an urgent call for new/novel antibacterial agents. In light of the circumstance, the present study demonstrates the in vitro and in vivo antibacterial activity of a phytochemical citral, with a particular emphasis to elucidate its mechanistic action against Gardnerella vaginalis -a potential cause of BV. Out of 21 phytochemicals screened initially against G. vaginalis, citral was envisaged to be a phenomenal antibacterial agent showing MIC and MBC at 128 µg/mL. Citral's rapid killing ability was revealed by a time-killing kinetics assay supported by CFU, signifying that it completely killed the given inoculum of planktonic G. vaginalis cells within 60 min. Further, citral was found to exhibit 1 min contact-killing efficacy together with mature-biofilm disintegrating ability at increasing MICs. To further understand the molecular action of citral, in vitro investigations such as ROS estimation, PI staining and intracellular protein release assay were performed, which demonstrated that citral deteriorated the membrane integrity of G. vaginalis. Galleria mellonella, a simple invertebrate model used to evaluate citral's non-toxic and antibacterial activity in vivo, demonstrates that citral completely restored the larvae from G. vaginalis infection. The metabolite level investigation using LC-MS revealed that citral had negative impact on biotin metabolism (via., biotin), spermidine metabolism (via., 5'-methylthioadenosine and spermidine) and nucleotide metabolism (via., guanine, adenine and uridine). Since that biotin is associated with seven different metabolic pathways, it is conceivable that citral could target biotin biosynthesis or its metabolism and as a result, disrupt other metabolic pathways, such as lipid and fatty acid synthesis, which is essential for the creation of cell membranes. Thus, the current study is the first of its kind to delineate the promising in vitro and in vivo antibacterial efficacy of citral and decipher its plausible antibacterial action mechanism through metabolomic approach, which concomitantly emphasizes citral as a viable natural therapeutic alternative to manage and control BV.

Exploring the Therapeutic Marvels: A Comprehensive Review on the Biological Potential of Quinoline-5,8-Dione.

Quinoline-5,8-diones, also referred to as 5,8-quinolinediones or quinolinequinones, have been researched extensively for their antiproliferative effects, where they displayed great results. Other than anticancer, they exhibit multiple activities such as antimalarial, antiviral, antibacterial, and antifungal activities. Natural quinolinequinones have also been known for their significant activities. The review highlights the diverse biological activities exhibited by synthetic quinoline- 5,8-diones over the past two decades. Continued research in this field is warranted to fully exploit the therapeutic potential of these intriguing compounds and their derivatives for future drug development. By comprehensively evaluating the therapeutic applications and biological activities of quinoline-5,8-dione derivatives, this review endeavors to provide researchers and practitioners with a valuable resource that will foster informed decision-making and inspire further investigations into harnessing the immense potential of this intriguing scaffold for the benefit of human health.

Natural antibiotics against antimicrobial resistance: sources and bioinspired delivery systems.

The current burden associated to multidrug resistance, and the emerging superbugs, result in a decreased and even loss of antibiotic efficacy, which poses significant challenges in the treatment of infectious diseases. This situation has created a high demand for the discovery of novel antibiotics that are both effective and safe. However, while antibiotics play a crucial role in preventing and treating diseases, they are also associated with adverse effects. The emergence of multidrug-resistant and the extensive appearance of drug-resistant microorganisms, has become one of the major hurdles in healthcare. Addressing this problem will require the development of at least 20 new antibiotics by 2060. However, the process of designing new antibiotics is time-consuming. To overcome the spread of drug-resistant microbes and infections, constant evaluation of innovative methods and new molecules is essential. Research is actively exploring alternative strategies, such as combination therapies, new drug delivery systems, and the repurposing of existing drugs. In addition, advancements in genomic and proteomic technologies are aiding in the identification of potential new drug targets and the discovery of new antibiotic compounds. In this review, we explore new sources of natural antibiotics from plants, algae other sources, and propose innovative bioinspired delivery systems for their use as an approach to promoting responsible antibiotic use and mitigate the spread of drug-resistant microbes and infections.

Mechanosynthesis of magnolol multicomponent crystalline solids for improved natural antibiotics and customizable release profiles.

Antibiotic is one of the most important discoveries in human and animal medicine. However, the inefficient use of antibiotics has caused widespread and persistent contamination of ecosystems, setting off microbial resistance storms. Magnolol is a botanical antibiotic, but poor physicochemical properties result in low bioavailability. Increasing solubility of magnolol can help to reduce the doses of medications to patients, minimize bothersome side effects. In this work, three novel multicomponent crystalline solids were synthesized from magnolol and isomeric coformers by mechanochemistry. It was found that the multicomponent crystalline solids achieved the customizable release profile of magnolol by manipulating the substituent positions of the isomers and complexation. Antibacterial activity test showed that bioactivity on two bacteria was considerably improved by designed MGN multicomponent crystals. In addition, the coformers controlled the dissolution behavior and further stabilized the improvement according to the variable statistical analysis. In conclusion, the properties of antibiotic multicomponent solids can be manipulated through the coformers. This provides an effective strategy for managing the release of drugs to meet individual biological differences and diverse therapeutic needs.

Antibacterial efficacy of indigenous Pakistani honey against extensively drug-resistant clinical isolates of Salmonella enterica serovar Typhi: an alternative option to combat antimicrobial resistance.

BACKGROUND: Extensively drug-resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) poses a grave threat to public health due to increased mortality and morbidity caused by typhoid fever. Honey is a promising antibacterial agent, and we aimed to determine the antibacterial activity of honey against XDR S. Typhi. METHODS: We isolated 20 clinical isolates of XDR S. Typhi from pediatric septicemic patients and determined the minimum inhibitory concentrations (MICs) of different antibiotics against the pathogens using the VITEK 2 Compact system. Antimicrobial-resistant genes carried by the isolates were identified using PCR. The antibacterial efficacy of five Pakistani honeys was examined using agar well diffusion assay, and their MICs and minimum bactericidal concentrations (MBCs) were determined with the broth microdilution method. RESULTS: All 20 isolates were confirmed as S. Typhi. The antibiogram phenotype was confirmed as XDR S. Typhi with resistance to ampicillin (≥ 32 µg/mL), ciprofloxacin (≥ 4 µg/mL), and ceftriaxone (≥ 4 µg/mL) and sensitivity to azithromycin (≤ 16 µg/mL) and carbapenems (≤ 1 µg/mL). Molecular conformation revealed the presence of blaTM-1, Sul1, qnrS, gyrA, gyrB, and blaCTX-M-15 genes in all isolates. Among the five honeys, beri honey had the highest zone of inhibition of 7-15 mm and neem honey had a zone of inhibition of 7-12 mm. The MIC and MBC of beri honey against 3/20 (15%) XDR S. Typhi isolates were 3.125 and 6.25%, respectively, while the MIC and MBC of neem were 3.125 and 6.25%, respectively, against 3/20 (15%) isolates and 6.25 and 12.5%, respectively, against 7/20 (35%) isolates. CONCLUSION: Indigenous honeys have an effective role in combating XDR S. Typhi. They are potential candidates for clinical trials as alternative therapeutic options against XDR S. Typhi isolates.

Lipid nanoparticles based on natural matrices with activity against multidrug resistant bacterial species.

Lately, the bacterial multidrug resistance has been a reason to public health concerning around world. The development of new pharmacology therapies against infections caused by multidrug-resistant bacteria is urgent. In this work, we developed 10 NLC formulations composed of essential oils (EO), vegetable butter and surfactant. The formulations were evaluated for long-term and thermal cycling stability studies in terms of (particle size, polydispersion index and Zeta potential). In vitro antimicrobial assays were performed using disk diffusion test and by the determination of the minimum inhibitory concentration (MIC) performed with fresh and a year-old NLC. The most promising system and its excipients were structurally characterized through experimental methodologies (FTIR-ATR, DSC and FE-SEM). Finally, this same formulation was studied through nanotoxicity assays on the chicken embryo model, analyzing different parameters, as viability and weight changes of embryos and annexes. All the developed formulations presented long-term physicochemical and thermal stability. The formulation based on cinnamon EO presented in vitro activity against strains of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from humans and in vivo biocompatibility. Considering these promising results, such system is able to be further tested on in vivo efficacy assays.

Anti-ultraviolet, antibacterial, and biofilm eradication activities against Cutibacterium acnes of melanins and melanin derivatives from Daedaleopsis tricolor and Fomes fomentarius.

Fomes fomentarius and Daedaleopsis tricolor produced significant amounts of water-insoluble melanins, and our previous study successfully enhanced their water solubility by arginine modification. This research aimed to investigate the anti-ultraviolet, antibacterial, and biofilm eradication activities of both the melanins and arginine-modified melanin (melanin derivatives) from these two fungi against an acne-causing bacterium (Cutibacterium acnes). Apart from these, the cytotoxicity of the melanins and melanin derivatives on human skin cells was also evaluated. Melanin derivatives of both two fungi showed significantly higher antibacterial and biofilm eradication activities compared with their original forms. Specifically, the MIC50 values of the melanin derivatives (1,000 µg/mL) are the same as those of erythromycin. Regarding biofilm eradication capacity, the MBEC50 value of D. tricolor melanin derivative (250 µg/mL) was just half of both erythromycin and F. fomentarius melanin derivative. However, it required a 2-fold higher concentration of melanin derivatives than erythromycin to inhibit 90% of the bacterial population and eradicate 90% of their biofilm. Regarding anti-ultraviolet activity, blending melanins or melanin derivatives with a moisturizer/sunscreen enhanced their UV light absorption and the sun protection factor (SPF) values. In addition, melanins showed better effects than their derivatives, and those of D. tricolor were better than F. fomentarius. Remarkably, adding D. tricolor melanin (10%) to a Nivea pure cream could turn this cream into a broad-spectrum sunscreen, with its SPF value and critical wavelength increasing from 7.74 and 338.67 to 14.02 and 377.0, respectively. In addition, adding melanin or a melanin derivative of D. tricolor to an Olay sunscreen enhanced the SPF and the critical wavelength of the sunscreen from 17.25 and 371.67 to 23.82 and 374 and 23.38 and 372, respectively. Notably, melanins and melanin derivatives showed no toxicity in human fibroblasts. The obtained data suggest that arginine modification significantly enhanced the antibacterial and biofilm eradication activities of melanins from D. tricolor and F. fomentarius. However, this is not the case when it comes to their anti-ultraviolet activities. In addition, melanin and melanin derivatives from D. tricolor are potential candidates for anti-acne sunscreen products and are worth further investigation.

Disease alleviating effects following prophylactic lemon and coriander essential oil treatment in mice with acute campylobacteriosis.

Introduction: Given the worldwide increasing prevalence of human Campylobacter jejuni infections and the emergence of multi-drug resistant enteropathogenic strains, antibiotic-independent approaches applying non-toxic natural compounds for the treatment and prophylaxis of campylobacteriosis appear utmost desirable. In our placebo-controlled intervention study, we surveyed potential disease-alleviating including anti-pathogenic and immune-modulatory effects upon prophylactic oral application of lemon-essential oil (LEM-EO) and coriander-essential oil (COR-EO) in acute experimental campylobacteriosis. Methods: Therefore, secondary abiotic IL-10-/- mice were orally challenged with either LEM-EO or COR-EO starting seven days prior to peroral C. jejuni infection. Results and discussion: Six days post-infection, slightly lower pathogen loads were assessed in the colon of mice from the LEM-EO as opposed to the COR-EO cohort if compared to placebo counterparts. Prophylactic application of both EOs improved the clinical outcome of acute campylobacteriosis which was paralleled by less distinct pathogen-induced colonic epithelial cell apoptosis. Moreover, mice subjected to LEM-EO and COR-EO prophylaxis displayed lower colonic numbers of macrophages/monocytes and of T lymphocytes, respectively, whereas in both verum groups, basal IL-6 and IFN-γ concentrations were measured in mesenteric lymph nodes on day 6 post-infection. The oral challenge with either EOs resulted in diminished secretion of distinct pro-inflammatory mediators in the kidney as well as serum samples derived from the infected mice. In conclusion, the results from our preclinical in vivo study provide evidence that LEM-EO and COR-EO constitute promising prophylactic measures to prevent severe campylobacteriosis which may help to reduce the risk for development of post-infectious sequelae in C. jejuni infected individuals.

Not only for Christmas: Prophylactic oral application of trans-cinnamaldehyde alleviates acute murine campylobacteriosis.

The prevalence of Campylobacter jejuni infections is increasing worldwide and responsible for significant morbidities and socioeconomic expenses. The rise in antimicrobial resistance of C. jejuni underscores the urge for evaluating antibiotics-independent compounds as therapeutic and preventive treatment options of human campylobacteriosis. Given its well-known anti-microbial and immune-modulatory properties we here surveyed the disease-modifying effects of trans-cinnamaldehyde pretreatment in experimental campylobacteriosis. Therefore, secondary abiotic IL-10-/- mice were orally challenged with trans-cinnamaldehyde starting 7 days prior C. jejuni infection. Whereas gastrointestinal colonization properties of the enteropathogens remained unaffected, trans-cinnamaldehyde pretreatment did not only improve clinical signs in infected mice, but also alleviated colonic epithelial cell apoptosis on day 6 post-infection. Furthermore, trans-cinnamaldehyde application resulted in less pronounced T cell responses in the colon that were accompanied by dampened proinflammatory mediator secretion in distinct intestinal compartments. Notably, the immune-modulatory effects of trans-cinnamaldehyde were not restricted to the intestinal tract but could also be observed in extra-intestinal organs such as the liver and kidneys. In conclusion, our preclinical placebo-controlled intervention study provides first evidence that due to its immune-modulatory effects, trans-cinnamaldehyde constitutes a promising prophylactic option to alleviate campylobacteriosis.

Prediction of Potential Natural Antibiotics Plants Based on Jamu Formula Using Random Forest Classifier.

Jamu is the traditional Indonesian herbal medicine system that is considered to have many benefits such as serving as a cure for diseases or maintaining sound health. A Jamu medicine is generally made from a mixture of several herbs. Natural antibiotics can provide a way to handle the problem of antibiotic resistance. This research aims to discover the potential of herbal plants as natural antibiotic candidates based on a machine learning approach. Our input data consists of a list of herbal formulas with plants as their constituents. The target class corresponds to bacterial diseases that can be cured by herbal formulas. The best model has been observed by implementing the Random Forest (RF) algorithm. For 10-fold cross-validations, the maximum accuracy, recall, and precision are 91.10%, 91.10%, and 90.54% with standard deviations 1.05, 1.05, and 1.48, respectively, which imply that the model obtained is good and robust. This study has shown that 14 plants can be potentially used as natural antibiotic candidates. Furthermore, according to scientific journals, 10 of the 14 selected plants have direct or indirect antibacterial activity.

Bee Bread as a Promising Source of Bioactive Molecules and Functional Properties: An Up-To-Date Review.

Bee bread is a natural product obtained from the fermentation of bee pollen mixed with bee saliva and flower nectar inside the honeycomb cells of a hive. Bee bread is considered a functional product, having several nutritional virtues and various bioactive molecules with curative or preventive effects. This paper aims to review current knowledge regarding the chemical composition and medicinal properties of bee bread, evaluated in vitro and in vivo, and to highlight the benefits of the diet supplementation of bee bread for human health. Bee bread extracts (distilled water, ethanol, methanol, diethyl ether, and ethyl acetate) have been proven to have antioxidant, antifungal, antibacterial, and antitumoral activities, and they can also inhibit α-amylase and angiotensin I-converting enzyme in vitro. More than 300 compounds have been identified in bee bread from different countries around the world, such as free amino acids, sugars, fatty acids, minerals, organic acids, polyphenols, and vitamins. In vivo studies have revealed the efficiency of bee bread in relieving several pathological cases, such as hyperglycemia, hyperlipidemia, inflammation, and oxidative stress.

Iron Deprivation by Oral Deferoxamine Application Alleviates Acute Campylobacteriosis in a Clinical Murine Campylobacter jejuni Infection Model.

The progressively rising food-borne Campylobacter jejuni infections pose serious health problems and socioeconomic burdens. Given that antibiotic therapy is not recommended for most campylobacteriosis patients, novel treatment options include strategies targeting iron homeostasis that impacts both C. jejuni virulence and inflammatory cell damage caused by toxic oxygen species. In our preclinical intervention study, we tested potential disease-alleviating effects upon prophylactic oral application of the iron-chelating compound desferoxamine (DESF) in acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10-/- mice received synthetic DESF via the drinking water starting seven days before oral infection with C. jejuni strain 81-176. Results revealed that the DESF application did not reduce gastrointestinal pathogen loads but significantly improved the clinical outcome of infected mice at day 6 post-infection. This was accompanied by less pronounced colonic epithelial cell apoptosis, attenuated accumulation of neutrophils in the infected large intestines and abolished intestinal IFN-γ and even systemic MCP-1 secretion. In conclusion, our study highlights the applied murine campylobacteriosis model as suitable for investigating the role of iron in C. jejuni infection in vivo as demonstrated by the disease-alleviating effects of specific iron binding by oral DESF application in acute C. jejuni induced enterocolitis.

Isolation and Identification of Bacteria with Surface and Antibacterial Activity from the Gut of Mediterranean Grey Mullets.

Fish gut represents a peculiar ecological niche where bacteria can transit and reside to play vital roles by producing bio-compounds with nutritional, immunomodulatory and other functions. This complex microbial ecosystem reflects several factors (environment, feeding regimen, fish species, etc.). The objective of the present study was the identification of intestinal microbial strains able to produce molecules called biosurfactants (BSs), which were tested for surface and antibacterial activity in order to select a group of probiotic bacteria for aquaculture use. Forty-two bacterial isolates from the digestive tracts of twenty Mediterranean grey mullets were screened for testing emulsifying (E-24), surface and antibiotic activities. Fifty percent of bacteria, ascribed to Pseudomonas aeruginosa, Pseudomonas sp., P. putida and P. anguilliseptica, P. stutzeri, P. protegens and Enterobacter ludwigii were found to be surfactant producers. Of the tested strains, 26.6% exhibited an antibacterial activity against Staphylococcus aureus (10.0 ± 0.0-14.5 ± 0.7 mm inhibition zone), and among them, 23.3% of isolates also showed inhibitory activity vs. Proteus mirabilis (10.0 ± 0.0-18.5 ± 0.7 mm inhibition zone) and 6.6% vs. Klebsiella pneumoniae (11.5 ± 0.7-17.5 ± 0.7 mm inhibition zone). According to preliminary chemical analysis, the bioactive compounds are suggested to be ascribed to the class of glycolipids. This works indicated that fish gut is a source of bioactive compounds which deserves to be explored.

Biologically Active Extracts from Different Medicinal Plants Tested as Potential Additives against Bee Pathogens.

Honey bees (Apis mellifera) perform pollination service for many agricultural crops and contribute to the global economy in agriculture and bee products. However, honey bee health is an ongoing concern, as illustrated by persistent local population decline, caused by some severe bee diseases (e.g., nosemosis, AFB, EFB, chalkbrood). Three natural recipes are in development based on the bioactive compounds of different plants extract (Agastache foeniculum, Artemisia absinthium, Evernia prunastri, Humulus lupulus, Laurus nobilis, Origanum vulgare and Vaccinium myrtillus), characterised by HPLC-PDA. The antimicrobial activity of these recipes was tested in vitro against Paenibacillus larvae, Paenibacillus alvei, Brevibacillus laterosporus, Enterococcus faecalis, Ascosphaera apis and in vivo against Nosema ceranae. A mix of 20% blueberry, 40% absinthium, 10% oakmoss, 10% oregano, 10% Brewers Gold hops, 5% bay laurel and 5% anise hyssop extract showed the strongest antibacterial and antifungal activity. Combing several highly active plant extracts might be an alternative treatment against bee-disease-associated parasites and pathogens, in particular to replace synthetic antibiotics.

Immune investigation of the honeybee Apis mellifera jemenitica broods: A step toward production of a bee-derived antibiotic against the American foulbrood.

Keeping honeybees healthy is essential, as bees are not only important for honey production but also cross-pollination of agricultural and horticultural crops; therefore, bees have a significant economic impact worldwide. Recently, the lethal disease, the American foulbrood (AFB), caused great losses of honeybee and decline of global apiculture. Recent studies have focused on using natural insect-derived antibiotics to overcome recently emerged AFB-resistance to conventional antibiotics. In support of these studies, here we investigate the possibility of producing bee-derived anti-AFB antibiotics from an indigenous honeybee, Apis mellifera jemenitica. The immune responses of the third instar stage were first induced against the standards Micrococcus luteus and Escherichia coli compared with the indigenous Paenibacillus larvae (ksuPL5). Data indicated a strong immune response against M. luteus, E. coli and P. larvae 24 h post-P. larvae-injection as revealed by the detection of lysozyme-like, cecropin-like and prophenoloxidase (PO) activities in the plasma of P. larvae-injected third instars. Nodulation activity against injected P. larvae as early as 4 h and peaking 48 h post-P. larvae injection were observed. Potentially active anti-P. larvae immune peptide fractions purified by high-performance liquid chromatography (HPLC) showed significant in vivo therapeutic effects on P. larvae-infected first instars. Mass spectrophotometric analysis and Orbitrap measurements of P. larvae-injected plasma indicated the expression of PO (Mr: 80 kDa), beta-1,3-glucan-binding protein (Mr: 52 kDa) and serine protease 44 isoform X1 (Mr: 46 kDa). This suggests that one or all of these immune peptides contribute to significant survivorship of P. larvae-infected broods, and could be a valuable clue in the search for honeybee-derived anti-AFB natural therapeutic agents. Further molecular characterization and description of the functional roles of these predicted antimicrobial peptides from both broods and adult honeybee may enrich the arsenal of insect-derived antibiotics of therapeutic purposes.

Garlic Essential Oil as Promising Option for the Treatment of Acute Campylobacteriosis-Results from a Preclinical Placebo-Controlled Intervention Study.

Since human infections with Campylobacter jejuni including antibiotic-resistant strains are rising worldwide, natural compounds might constitute promising antibiotics-independent treatment options for campylobacteriosis. Since the health-beneficial properties of garlic have been known for centuries, we here surveyed the antimicrobial and immune-modulatory effects of garlic essential oil (EO) in acute experimental campylobacteriosis. Therefore, secondary abiotic IL-10-/- mice were orally infected with C. jejuni strain 81-176 and garlic-EO treatment via the drinking water was initiated on day 2 post-infection. Mice from the garlic-EO group displayed less severe clinical signs of acute campylobacteriosis as compared to placebo counterparts that were associated with lower ileal C. jejuni burdens on day 6 post-infection. Furthermore, when compared to placebo application, garlic-EO treatment resulted in alleviated colonic epithelia cell apoptosis, in less pronounced C. jejuni induced immune cell responses in the large intestines, in dampened pro-inflammatory mediator secretion in intestinal and extra-intestinal compartments, and, finally, in less frequent translocation of viable pathogens from the intestines to distinct organs. Given its potent immune-modulatory and disease-alleviating effects as shown in our actual preclinical placebo-controlled intervention study, we conclude that garlic-EO may be considered as promising adjunct treatment option for acute campylobacteriosis in humans.