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Biofilm-formed enterococcal urinary tract clinical isolates (n = 92) were used for studying the antibiofilm activity of cinnamon, ginger, and chemical AgNPs. The average particle sizes of cinnamon, ginger, and chemical AgNPs were 8.7, 41.98, and 55.7 nm, respectively. The results of Fourier transform infrared analysis revealed that phytocompounds, such as cinnamaldehyde and gingerol, were the main compounds incorporated in the synthesis of cinnamon and ginger AgNPs, respectively. The purity and crystalline nature of the AgNPs have been confirmed by energy dispersive X-ray and X-ray Diffraction analysis. The results of antimicrobial activity showed that MIC of ginger, cinnamon, and chemical AgNPs were 37.64, 725.7, and 61.08 μg/ml, respectively. On studying the antibiofilm activity of AgNPs at sub-MIC values (1/2, 1/4, and 1/8 MIC), the results revealed that it was concentration dependent. Therefore, further studies were carried out to evaluate the antibiofilm activity of AgNPs at a concentration of 18 μg/ml. The results showed that ginger and chemical AgNPs reduced the formed biofilm to 39.14% and 65.32% and the number of adherent cells on the urinary catheter surface to 42.73% and 69.84%, respectively, as compared to that of the control, while cinnamon AgNPs showed no significant activity. Accordingly, ginger AgNPs had the most potent antibacterial and antiadherent activity against biofilm-associated enterococcal isolates.

Strong biofilm-forming Enterococcus feacalis urinary tract pathogens (n = 35) were used to determine the lytic spectrum of six bacteriophages isolated from sewage samples. Only 17 Enterococcus feacalis isolates gave lytic zones with the tested bacteriophages from which five isolates were susceptible to all of them. The isolated enterococcal phages are characterized by wide range of thermal (30–90 °C) and pH (3–10) stability. They belong to order Caudovirales, from which four bacteriophages (EPA, EPB, EPD, EPF) belong to family M yoviridae and two (EPC, EPE) belong to family Siphoviridae. In addition, they have promising antibiofilm activity against the tested strong-forming biofilm E. faecalis isolates. The enterococcal phages reduced the formed and preformed biofilms to a range of 38.02–45.7% and 71.0–80.0%, respectively, as compared to the control. The same promising activities were obtained on studying the anti-adherent effect of the tested bacteriophages on the adherence of bacterial cells to the surface of urinary catheter segments. They reduced the number of adherent cells to a range of 30.8–43.8% and eradicated the pre-adherent cells to a range of 48.2–71.1%, as compared to the control. Overall, the obtained promising antibiofilm activity makes these phages good candidates for application in preventing and treating biofilm associated Enterococcus faecalis infections.

Background Paromomycin is a 2-deoxystreptamine aminocyclitol aminoglycoside antibiotic with broad spectrum activity against Gram-negative, Gram-positive bacteria and many protozoa. This study introduces a strategy for paromomycin production through solid-state fermentation using Streptomyces rimosus subsp. paromomycinus NRRL 2455. Solid state fermentation has gained enormous attention in the development of several products because of their numerous advantages over submerged liquid fermentation. After selecting the best solid substrate, a time course study of paromomycin production was carried out followed by optimization of environmental conditions using response surface methodology. Paromomycin yields obtained using this technique were also compared to those obtained using submerged liquid fermentation. Results Upon screening of 6 different substrates, maximum paromomycin concentration (0.51 mg/g initial dry solids) was obtained with the cost-effective agro-industrial byproduct, corn bran, impregnated with aminoglycoside production media. Optimization of environmental conditions using D-optimal design yielded a 4.3-fold enhancement in paromomycin concentration reaching 2.21 mg/g initial dry solids at a pH of 8.5, inoculum size of 5% v/w and a temperature of 30 °C. Conclusion Compared to submerged liquid fermentation, solid state fermentation resulted in comparable paromomycin concentrations, cost reduction of raw materials, less energy consumption and waste water discharge, which have major implications in industrial fermentation. Therefore, solid state fermentation is a promising alternative to submerged liquid fermentation for paromomycin production. To the best of our knowledge, this is the first report on the optimized paromomycin production through solid state fermentation process.

Skin infections caused by strong biofilm Pseudomonas aeruginosa (P. aeruginosa) are considered a serious public health issue because of the increased resistance toward the currently available antibiotics. Consequently, innovative therapeutic strategies have emerged to address these challenging infections. Among them, phage therapy stands out, in which highly potent lytic bacteriophages (phages) are specifically selected to target and eradicate the responsible pathogens. In this study, Pseudomonas phage E21 was recovered from sewage, and it genetically belongs to the Lavrentievirus genus, Casjensviridae family. The genetic characterization of the isolated phage reveals the presence of highly potent lytic enzymes, which play a critical role in effectively suppressing the growth of the targeted pathogens. The phage has high stability patterns over a wide range of temperatures and pH values (65 ℃ and 3–11). Carboxymethylcellulose was used to formulate a hydrogel for the evaluation of the bacteriophage’s efficacy against biofilm-associated wound infection in a suitable animal model. The result of the preclinical study confirmed the efficacy of isolated phage in the therapy of biofilm-associated wound infection.

Mushrooms are nutritious foods that are widely cultivated all over the world. They are rich in a range of compounds linked to improving functions of the immune system including carotenoids, alkaloids, lectins, enzymes, folates, fats, organic acids, minerals, polysaccharides, phenolics, proteins, tocopherols, terpenoids, and volatile compounds. In this study we investigated, the immunomodulatory activity in rats of the aqueous extracts of five of the most common edible mushrooms belonging to Family Basidiomycota-white-rot fungi including, Lentinula edodes, Agaricus bisporus , Pleurotus ostreatus , Pleurotus columbinus, and Pleurotus sajor-caju . Male Wistar albino rats were assigned to thirteen groups and Immunosuppression was induced by oral administration of dexamethasone (0.1 mg/kg), followed by oral administration of the mushroom extracts at low (200 mg/kg) and high (400 mg/kg) doses. A positive control group received the immune stimulant Echinacea extract Immulant® at (30 mg/kg), while the negative control group received only saline. From each animal, in each group, blood samples were collected after 15 days for complete blood counts and for measurement of immunologic parameters, including lysozyme activity, nitric oxide (NO) production and serum cytokines including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin 1 beta (IL-1β) levels. Results have shown that white blood cells (WBCs) and lymphocytic counts were significantly boosted by high doses of each of the five mushroom extracts (207–289% increase for WBC and 153–175% for lymphocytes) with a significant increase in lysozyme activity (110–136% increase), NO concentration (159–232% increase) and cytokines as compared to the negative control group. Histopathological examination of the rats' spleen and thymus tissues has shown marked lymphocytic proliferation that was more obvious at the higher doses. In conclusion, our results showed that the five edible mushroom extracts revealed significant immunostimulatory effects preclinically particularly, at the higher doses (400 mg/kg) which can be considered the effective dose.

Marine microorganisms residing in the Red Sea have been recognized as valuable sources of novel natural products with potential medical applications. One distinct bacterial isolate coded MMM3 was isolated from the marine tunicate Phallusia nigra , gathered from the Egyptian coast of the Red Sea. The present study aimed to identify and assess the isolated strain’s biological activities. After genomic extraction and PCR amplification, the bacterial strain was identified through 16 S rRNA gene sequencing as Heyndrickxia ginsengihumi and deposited in (NCBI) GenBank database under the accession code PX237387. The tested isolate was cultivated in R2A liquid medium for ten days at 25 °C in a shaking incubator set at 220 rpm. The crude extract exhibited effective COX-2 inhibition and antioxidant activity with IC₅₀ value of 107.07 and 451.75 µg/ml, respectively. The crude extract exerted antifungal effect (inhibition zone of 9 mm) against Candida albicans ATCC 10,231. In addition, the crude extract demonstrated significant cytotoxic activities against HepG2, A-549, MCF-7 and HCT-116 cell lines with IC 50 values of 54.67 ± 1.05, 60.19 ± 1.23, 108.79 ± 2.08, and 73.57 ± 1.48 µg/mL, respectively. Regarding the chemical characterization of the crude extract, LC-MS analysis indicated diverse secondary metabolites including linoleic acid, myristoyl glucose-3-phosphate, and 2-acetoxy-4-pentadecylbenzoic acid. The identified metabolites suggest a synergistic contribution to the biological activities of the isolated strain, highlighting its potential as a source of bioactive compounds. The results indicated that the bacteria isolated from Red Sea coast is a promising source of bioactive molecules with medical applications.

A high cellulase-producing bacterial isolate TS4 was recovered from an Egyptian soil sample and identified using 16S rRNA gene sequencing as Streptomyces thermodiastaticus. One-factor-at-a-time (OFAT) preliminary studies were carried out to determine the key factors affecting cellulase production by S. thermodiastaticus and their optimum ranges. The initial pH of the medium, carboxymethyl cellulose (CMC), tryptone, and NaCl concentrations were further optimized using a response surface Central Composite design. Fermentation under optimized variables of initial pH 6.0, presence of CMC, tryptone, and NaCl at concentrations of 2%, 0.03%, and 0.12%, respectively, resulted in 3.24 fold increase in cellulase productivity (2023 U/L) as compared to that under basal conditions (625 U/L). Cellulase production was also improved with a 4 Kilogray (KGy) dosage of gamma radiation. In comparison to the wild-type strain under basal circumstances, S. thermodiastaticus produced 5.1 fold more cellulase after a combination of model-based optimization and gamma radiation mutation. Cellulase was partially purified using ammonium sulfate precipitation followed by dialysis. The resulting cellulase was 1.74 times purified and its specific activity was 4.21 U/mg. The molecular weight of cellulase is 63 kDa as indicated by SDS-PAGE and zymogram. Its maximum activity was achieved at 60 °C and pH 5.0. In addition, it showed outstanding thermo-tolerance as it could retain its full activity after a 12-h incubation at 90 °C.

Background Response surface methodology (RSM) employing Box-Behnken design was used to optimize the environmental factors for the production of paromomycin, a 2 deoxystreptamine aminocyclitol aminoglycoside antibiotic, (2DOS-ACAGA) from Streptomyces (S.) rimosus NRRL 2455. Emergence of bacterial resistance caught our attention to consider the combination of antimicrobial agents. The effect of paromomycin combination with other antimicrobial agents was tested on some multiple drug resistant isolates. To the best of our knowledge, this is the first report on optimization of paromomycin production from S. rimosus NRRL 2455. A Quadratic model and response surface method were used by choosing three model factors; pH, incubation time and inoculum size. A total of 17 experiments were done and the response of each experiment was recorded. Concerning the effect of combining paromomycin with different antimicrobial agents, it was tested using the checkerboard assay against six multidrug resistant (MDR) pathogens including; Pseudomonas (P.) aeruginosa (2 isolates), Klebsiella (K.) pneumoniae , Escherichia (E.) coli , methicillin sensitive Staphylococcus aureus (MSSA) and methicillin resistant Staphylococcus aureus (MRSA). Paromomycin was tested in combination with ceftriaxone, ciprofloxacin, ampicillin/sulbactam, azithromycin, clindamycin and doxycycline. Results The optimum conditions for paromomycin production were a pH of 6, an incubation time of 8.5 days and an inoculum size of 5.5% v /v using the optimized media (soybean meal 30 g/L, NH 4 CL 4 g/L, CaCO 3 5 g/L and glycerol 40 ml/L), 28 °C incubation temperature, and 200 rpm agitation rate that resulted in 14 fold increase in paromomycin production as compared to preliminary fermentation level using the basal medium. The tested antibiotic combinations showed either synergistic effect on paromomycin activity on most of the tested MDR pathogens (45.83%), additive effect in 41.67% or indifferent effect in 12.5%. Conclusion RSM using multifactorial design was a helpful and a reliable method for paromomycin production. Paromomycin combination with ceftriaxone, ciprofloxacin, ampicillin/sulbactam, azithromycin, clindamycin or doxycycline showed mostly synergistic effect on certain selected clinically important MDR pathogens.

In this study, we investigated aqueous extracts of three edible mushrooms: Agaricus bisporus (white button mushroom), Pleurotus columbinus (oyster mushroom), and Pleurotus sajor-caju (grey oyster mushroom). The extracts were biochemically characterized for total carbohydrate, phenolic, flavonoid, vitamin, and protein contents besides amino acid analysis. Triple TOF proteome analysis showed 30.1% similarity between proteomes of the two Pleurotus spp. All three extracts showed promising antiviral activities. While Pleurotus columbinus extract showed potent activity against adenovirus (Ad7, selectivity index (SI) = 4.2), Agaricus bisporus showed strong activity against herpes simplex II (HSV-2; SI = 3.7). The extracts showed low cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs) and moderate cytotoxicity against prostate (PC3, DU-145); colorectal (Colo-205); cecum carcinoma (LS-513); liver carcinoma (HepG2); cervical cancer (HeLa); breast adenocarcinoma (MDA-MB-231 and MCF-7) as well as leukemia (CCRF-CEM); acute monocytic leukemia (THP1); acute promyelocytic leukemia (NB4); and lymphoma (U937) cell lines. Antioxidant activity was evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging, 2,2′-Azinobis-(3-Ethylbenzthiazolin-6-Sulfonic Acid) ABTS radical cation scavenging, and oxygen radical absorbance capacity (ORAC) assays. The three extracts showed potential antioxidant activities with the maximum activity recorded for Pleurotus columbinus (IC50 µg/mL) = 35.13 ± 3.27 for DPPH, 13.97 ± 4.91 for ABTS, and 29.42 ± 3.21 for ORAC assays.

Anecdotal evidence showed a negative correlation between Bacille Calmette-Guérin (BCG) vaccination and incidence of COVID-19. Incidence of the disease in children is much lower than in adults. It is hypothesized that BCG and other childhood vaccinations may provide some protection against SARS-CoV-2 infection through trained or adaptive immune responses. Here, we tested whether BCG, Pneumococcal, Rotavirus, Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenzae, Hepatitis B, Meningococcal, Measles, Mumps, and Rubella vaccines provide cross-reactive neutralizing antibodies against SARS-CoV-2 in BALB/c mice. Results indicated that none of these vaccines provided antibodies capable of neutralizing SARS-CoV-2 up to seven weeks post vaccination. We conclude that if such vaccines have any role in COVID-19 immunity, this role is not antibody-mediated.