Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of other medicinal applications. In the battle against microbes, antibiotics have certainly been a blessing to human civilization by saving millions of lives. Globally, infections caused by multidrug-resistant (MDR) bacteria are on the rise. Antibiotics are being used to combat diversified bacterial infections. Synthetic biology techniques, in combination with molecular, functional genomic, and metagenomic studies of bacteria, plants, and even marine invertebrates are aimed at unlocking the world's natural products faster than previous methods of antibiotic discovery. There are currently only few viable remedies, potential preventive techniques, and a limited number of antibiotics, thereby necessitating the discovery of innovative medicinal approaches and antimicrobial therapies. MDR is also facilitated by biofilms, which makes infection control more complex. In this review, we have spotlighted comprehensively various aspects of antibiotics viz. overview of antibiotics era, mode of actions of antibiotics, development and mechanisms of antibiotic resistance in bacteria, and future strategies to fight the emerging antimicrobial resistant threat.

Background: Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Methods: Semi-crystalline nanoparticles (NPs) of 90–110 nm diameter for APSP and 65–75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. Results: The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Conclusion: Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug.

The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region.

Background: Silibinin has gained in importance in the past few decades as a hepatoprotector and is used widely as oral therapy for toxic liver damage, liver cirrhosis, and chronic inflammatory liver diseases, as well as for the treatment of different types of cancers. Unfortunately, it has low aqueous solubility and inadequate dissolution, which results in low oral bioavailability. Materials and methods: In this study, nanoparticles (NPs) of silibinin, which is a hydrophobic drug, were manufactured using two cost-effective methods. Antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN) were used. The prepared NPs were characterized using different analytical techniques such as scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffractometry (XRD) and were sifted for their bioavailability through in vitro dissolution and solubility studies. Moreover, the prepared NPs were evaluated for antimicrobial activity against a battery of bacteria and yeast. Results: DSC and XRD studies indicated that the prepared NPs were amorphous in nature, with more solubility and dissolution compared to the crystalline form of this drug. NPs prepared through the EPN method had better results than those prepared using the APSP method. Antimicrobial activities of the NPs were improved compared to the unprocessed drugs, while having comparable activities to standard antimicrobial drugs. Conclusion: Results indicate that the NPs have significantly increased solubility, dissolution rate, and antimicrobial activities due to the conversion of crystalline structure into amorphous form.

Escherichia albertii is characterized as an emerging pathogen, causing enteric infections. It is responsible for high mortality rate, especially in children, elderly, and immunocompromised people. To the best of our knowledge, no vaccine exists to curb this pathogen. Therefore, in current study, we aimed to identify potential vaccine candidates and design chimeric vaccine models against Escherichia albertii from the analysis of publicly available data of 95 strains, using a reverse vaccinology approach. Outer-membrane proteins (n = 4) were identified from core genome as vaccine candidates. Eventually, outer membrane Fimbrial usher (FimD) protein was selected as a promiscuous vaccine candidate and utilized to construct a potential vaccine model. It resulted in three epitopes, leading to the design of twelve vaccine constructs. Amongst these, V6 construct was found to be highly immunogenic, non-toxic, non-allergenic, antigenic, and most stable. This was utilized for molecular docking and simulation studies against six HLA and two TLR complexes. This construct can therefore be used for pan-therapy against different strains of E. albertii and needs to be tested in vitro and in vivo.

Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver–Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis–Menten kinetics. Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC₅₀ of 343.45 and 422.98 μM, respectively, against AChE enzyme. Similarly, both the compounds showed IC₅₀ of 276.86 and 357.91 μM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC₅₀ of 157.71 and 471.79 μM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC₅₀ values of 297.98, 332.94, and 825.92 μM against DPPH, ABTS, and H₂O₂ free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.