Synergetic Inactivation Mechanism of Protocatechuic Acid and High Hydrostatic Pressure against Escherichia coli O157:H7

With the wide application of high hydrostatic pressure (HHP) technology in the food industry, safety issues regarding food products, resulting in potential food safety hazards, have arisen. To address such problems, this study explored the synergetic bactericidal effects and mechanisms of protocatechuic acid (PCA) and HHP against Escherichia coli O157:H7. At greater than 200 MPa, PCA (1.25 mg/mL for 60 min) plus HHP treatments had significant synergetic bactericidal effects that positively correlated with pressure. After a combined treatment at 500 MPa for 5 min, an approximate 9.0 log CFU/mL colony decline occurred, whereas the individual HHP and PCA treatments caused 4.48 and 1.06 log CFU/mL colony decreases, respectively. Mechanistically, membrane integrity and morphology were damaged, and the permeability increased when E. coli O157: H7 was exposed to the synergetic stress of PCA plus HHP. Inside cells, the synergetic treatment additionally targeted the activities of enzymes such as superoxide dismutase, catalase and ATPase, which were inhibited significantly (p ≤ 0.05) when exposed to high pressure. Moreover, an analysis of circular dichroism spectra indicated that the synergetic treatment caused a change in DNA structure, which was expressed as the redshift of the characteristic absorption peak. Thus, the synergetic treatment of PCA plus HHP may be used as a decontamination method owing to the good bactericidal effects on multiple targets.

Small molecule targeting amyloid fibrils inhibits Streptococcus mutans biofilm formation

Amyloid fibrils are important scaffold in bacterial biofilms. Streptococcus mutans is an established cariogenic bacteria dwelling within biofilms, and C123 segment of P1 protein is known to form amyloid fibrils in S. mutans biofilms, among which C3 segment could serve as a promising anti-amyloid target due to its critical role in C123-P1 interactions. Recently, small molecules have been found to successfully inhibit biofilms by targeting amyloid fibrils. Thus, our study aimed to screen small molecules targeting C3 segment with the capacity to influence amyloid fibrils and S. mutans biofilms. In silico screening was utilized to discover promising small molecules, which were evaluated for their effects on bacterial cells and amyloid fibrils. We selected 99 small molecules and enrolled 55 small molecules named D1–D55 for crystal violet staining. Notably, D25 selectively inhibit S. mutans biofilms but had no significant influence on biofilms formed by Streptococcus gordonii and Streptococcus sanguinis, and D25 showed no bactericidal effects and low cytotoxicity. In addition, amyloid fibrils in free-floating bacteria, biofilms and purified C123 were quantified with ThT assays, and the differences were not statistically significant in the presence or absence of D25. Morphological changes of amyloid fibrils were visualized with TEM images, where amorphous aggregates were obvious coupled with long and atypical amyloid fibrils. Moreover, amyloid-related genes were upregulated in response to D25. In conclusion, D25 is a promising antimicrobial agent with the capacity to influence amyloid fibrils and inhibit S. mutans biofilms.

Synthesis of Some Quinoxaline Sulfonamides as a Potential Antibacterial Agent

Aims: This studies aims at the synthesis of new heterocyclic systems and study its biological and pharmacological properties. Objective: This study was designed to synthesized some quinoxaline-2,3-dione with sulfonamide moiety, characterize the synthesized compounds, and study the antimicrobial properties of the synthesized compounds on some bacterial strains. Materials and Methods: Six quinoxaline-6-sulfonohydrazone derivatives were synthesized by reacting quinoxaline-6-sulfonohydrazine with some substituted benzaldehydes and ketones. The compounds were tested for their potential antibacterial properties. Results: All the test compounds possessed promising antibacterial property against a panel of bacterial strains used for this study. The MIC values exhibited by these compounds ranged between 0.0313 and 0.250 mg/mL. Among the compounds tested, compound 2 showed appreciable antibacterial activity. Discussion and Conclusion: The study concluded that all the compounds exhibited appreciable bactericidal effects towards all the bacterial strains, particularly, compound 2 This is an indication that such compounds possessing broad spectrum activities will be useful in formulating antimicrobial compounds which could be used to treat infections caused by pathogens that are now developing resistance against the available antibiotics.

Design, Synthesis, Reactions and Antibacterial Properties of 2-hydrazinyl-3-methyl-6-nitroquinoxaline Derivatives

Aims: This aims of this study was to synthesis new quinoxaline-based heterocycles and study its antibacterial properties. Objective: This study was designed to synthesis some 3-methyl-6-nitroquinoxaline-2-one with hydrazine moiety, characterize the synthesized compounds, and study their antibacterial properties on some bacterial strains. Materials and Methods: Six 3-methylquinoxaline-2-hydrazone derivatives were synthesized by reacting 2-hydrazinyl-3-methyl-6-nitroquinoxaline with various substituted acetophenones. The hydrazones were screened for their potential antibacterial properties. Results: All the test compounds were found to possessed promising antibacterial properties against a panel of bacterial strains screened for this study. The MIC values exhibited by these compounds ranged between 0.0313 and 0.250 mg/mL. The lowest MBC of the compounds against the test organism was 0.0625 mg/mL while the highest MBC was 0.250 mg/mL. Discussion and Conclusion: The study concluded that all the compounds exhibited appreciable bactericidal effects against all the bacterial strains, which is an indication that such synthetic compounds possessed broad spectrum activities and such compounds could be useful in formulation of antibacterial compounds which could be used to mitigates infections caused by pathogens that are now developing resistance against the available antibiotics.

Design, Synthesis and Antibacterial Activity of some 3,6-Dimethlyquinoxaline-2-Hydrazone Derivatives

Aims: This aims of this study was to continue the effort to synthesis new quinoxaline-based heterocycles and study its antibacterial properties. Objective: This study was designed to reacts 3,6-dimethylquinoxaline-2-hydrazine with some substituted aromatic ketones and study their antibacterial properties on some locally and clinically isolated bacterial strains. Materials and Methods: Five 3,6-dimethylquinoxaline-2-hydrazone derivatives were synthesized from the reactions of 3,6-dimethylquinoxaline-2-hydrazine with various substituted aromatic ketones. The products were then tested for their potential antibacterial properties. Results: All the synthesized compounds were found to be active against all the bacterial strains investigated in this study. It was observed that the zones of inhibition observed for the synthesized compounds against the test organisms ranged between 15 mm and 38 mm. The MIC observed for the synthesized compounds ranged between 0.0313mg/mL and 0.125 mg/mL, while that of the standard antibiotic, streptomycin, varied between 0.0313 mg/mL and 0.500 mg/mL and those observed for tetracycline falls between 0.0313 mg/mL and 0.500 mg/mL. The minimum bactericidal concentrations exhibited by the synthesized compounds ranged between 0.0625 mg/mL and 0.250 mg/mL Discussion and conclusion: The study concluded that all the compounds exhibited appreciable bactericidal effects against all the bacterial strains, which is an indication that such synthetic compounds possessed broad spectrum activities and such compounds could be useful in formulation of antibacterial compounds which could be used to mitigates infections caused by pathogens that are now developing resistance against the available antibiotics.

ISMN-loaded PLGA-PEG nanoparticles conjugated with anti-Staphylococcus aureus α-toxin inhibit Staphylococcus aureus biofilms in chronic rhinosinusitis

Background: Staphylococcus aureus biofilms were linked to negative postsurgical outcomes of chronic rhinosinusitis (CRS). This study aims to develop a targeted nanoparticle and characterize its bactericidal effects. Methods: The authors prepared ISMN-loaded poly-lactide-co-glycolide acid (PLGA) and polyethylene glycol (PEG) nanoparticles conjugated with anti- S. aureus α-toxin (AA; ISMN-PLGA-PEG-AA), and determined its bactericidal and toxic effects. The antibiofilm propriety of ISMN-PLGA-PEG-AA was further investigated in a sheep CRS model. Results: ISMN-PLGA-PEG-AA had no toxic effect, while ISMN, ISMN-PLGA-PEG and ISMN-PLGA-PEG-AA had significantly anti- S. aureus effects. The blood concentrations and mRNA levels in sinus tissues of IL-4, IL-8 and IFN-γ in the sheep CRS model were significantly low. Conclusion: ISMN-PLGA-PEG-AA can effectively inhibit S. aureus biofilm, and is a promising drug for CRS treatment.

Novel Virulent Bacteriophage SG005, Which Infects Streptococcus gordonii, Forms a Distinct Clade among Streptococcus Viruses

Bacteriophages are viruses that specifically infect bacteria and are classified as either virulent phages or temperate phages. Despite virulent phages being promising antimicrobial agents due to their bactericidal effects, the implementation of phage therapy depends on the availability of virulent phages against target bacteria. Notably, virulent phages of Streptococcus gordonii, which resides in the oral cavity and is an opportunistic pathogen that can cause periodontitis and endocarditis have previously never been found. We thus attempted to isolate virulent phages against S. gordonii. In the present study, we report for the first time a virulent bacteriophage against S. gordonii, <phi>SG005, discovered from drainage water. <phi>SG005 is composed of a short, non-contractile tail and a long head, revealing Podoviridae characteristics via electron microscopic analysis. In turbidity reduction assays, <phi>SG005 showed efficient bactericidal effects on S. gordonii. Whole-genome sequencing showed that the virus has a DNA genome of 16,127 bp with 21 coding sequences. We identified no prophage-related elements such as integrase in the <phi>SG005 genome, demonstrating that the virus is a virulent phage. Phylogenetic analysis indicated that <phi>SG005 forms a distinct clade among the streptococcus viruses and is positioned next to streptococcus virus C1. Molecular characterization revealed the presence of an anti-CRISPR (Acr) IIA5-like protein in the <phi>SG005 genome. These findings facilitate our understanding of streptococcus viruses and advance the development of phage therapy against S. gordonii infection.

(−)-Brunneusine, a new phenolic compound with antibacterial properties in aqueous medium from the leaves of Agelanthus brunneus (Engl.) Tiegh (LORANTHACEAE)

Agelanthus brunneus (Loranthaceae) is a hemiparasitic plant growing on Senna siamea (Fabaceae). The chemical investigation of its leaves and flowers led to the isolation of one new phenolic compound namely (−)-brunneusine (1), together with 13 known compounds. The crude leaves and flowers extracts (CLE and CFLE) with their ethyl acetate fractions (EAFL and EAFFL) and some isolated compounds (1–3; 8–9 and 11–14) have been tested on four bacterial species of sanitary importance isolated in an aquatic environment. All the samples except compound 3 showed antibacterial activity with MICs ranging from 0.43 to 8.88.103 µg/mL and MBCs from 0.43 to 3.55.103 µg/mL. Compounds 9 and 14 showed better activity on all bacterial species tested with MICs ranging from 0.43 to 27.77 µg/mL. Only CLE, EAFL and compounds 14, 2, 8 and 9 showed bactericidal effects on all bacterial species tested.