Current developments and prospects of the antibiotic delivery systems.

Antibiotics have remained the cornerstone for the treatment of bacterial infections ever since their discovery in the twentieth century. The uproar over antibiotic resistance among bacteria arising from genome plasticity and biofilm development has rendered current antibiotic therapies ineffective, urging the development of innovative therapeutic approaches. The development of antibiotic resistance among bacteria has further heightened the clinical failure of antibiotic therapy, which is often linked to its low bioavailability, side effects, and poor penetration and accumulation at the site of infection. In this review, we highlight the potential use of siderophores, antibodies, cell-penetrating peptides, antimicrobial peptides, bacteriophages, and nanoparticles to smuggle antibiotics across impermeable biological membranes to achieve therapeutically relevant concentrations of antibiotics and combat antimicrobial resistance (AMR). We will discuss the general mechanisms via which each delivery system functions and how it can be tailored to deliver antibiotics against the paradigm of mechanisms underlying antibiotic resistance.

Zingerone inhibits biofilm formation and enhances antibiotic efficacy against Salmonella biofilm.

Salmonella enterica serovar Typhi is a significant cause of typhoid fever and a major public health problem. The ability of S. Typhi to form biofilms on living and non-living surfaces results in antibiotic resistance and poses a major challenge in health care. In this study, we assessed the ability of zingerone alone and in combination with antibiotics against the motility phenotypes and biofilm-forming ability of S. Typhi. Results showed that zingerone effectively reduced the swimming, swarming, and twitching phenotypes and exhibited biofilm inhibition potential. Moreover, zingerone enhanced the antibiofilm activity of ciprofloxacin and kanamycin. Microscopic analysis revealed a thinner biofilm in the presence of zingerone, which may have enhanced the antibiofilm efficacy of the antibiotics. The microscopic analysis showed that the presence of zingerone resulted in a reduction in the thickness of the biofilm, potentially increasing the antibiofilm efficacy of the antibiotics. In silico molecular docking and simulation studies further indicated that zingerone may bind to the fimbriae subunits (FimA, FimC, FimH, and FimY) of S. Typhi and form stable interactions. These findings provide important insights into the potential of zingerone to target biofilm-associated Salmonella infections. Further research is considered a promising option for designing innovative approaches to prevent infections associated with biofilms. Schematic representation of the role of zingerone in biofilm, motility inhibition and molecular interactions with biofilm associated proteins.

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria.

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.

Bacteriophages in nature: recent advances in research tools and diverse environmental and biotechnological applications.

Bacteriophages infect and replicate within bacteria and play a key role in the environment, particularly in microbial ecosystems and bacterial population dynamics. The increasing recognition of their significance stems from their wide array of environmental and biotechnological uses, which encompass the mounting issue of antimicrobial resistance (AMR). Beyond their therapeutic potential in combating antibiotic-resistant infections, bacteriophages also find vast applications such as water quality monitoring, bioremediation, and nutrient cycling within environmental sciences. Researchers are actively involved in isolating and characterizing bacteriophages from different natural sources to explore their applications. Gaining insights into key aspects such as the life cycle of bacteriophages, their host range, immune interactions, and physical stability is vital to enhance their application potential. The establishment of diverse phage libraries has become indispensable to facilitate their wide-ranging uses. Consequently, numerous protocols, ranging from traditional to cutting-edge techniques, have been developed for the isolation, detection, purification, and characterization of bacteriophages from diverse environmental sources. This review offers an exploration of tools, delves into the methods of isolation, characterization, and the extensive environmental applications of bacteriophages, particularly in areas like water quality assessment, the food sector, therapeutic interventions, and the phage therapy in various infections and diseases.

Recent Advances in Monoclonal Antibody-Based Approaches in the Management of Bacterial Sepsis.

Sepsis is a life-threatening condition characterized by an uncontrolled inflammatory response to an infectious agent and its antigens. Immune cell activation against the antigens causes severe distress that mediates a strong inflammatory response in vital organs. Sepsis is responsible for a high rate of morbidity and mortality in immunosuppressed patients. Monoclonal antibody (mAb)-based therapeutic strategies are now being explored as a viable therapy option for severe sepsis and septic shock. Monoclonal antibodies may provide benefits through two major strategies: (a) monoclonal antibodies targeting the pathogen and its components, and (b) mAbs targeting inflammatory signaling may directly suppress the production of inflammatory mediators. The major focus of mAb therapies has been bacterial endotoxin (lipopolysaccharide), although other surface antigens are also being investigated for mAb therapy. Several promising candidates for mAbs are undergoing clinical trials at present. Despite several failures and the investigation of novel targets, mAb therapy provides a glimmer of hope for the treatment of severe bacterial sepsis and septic shock. In this review, mAb candidates, their efficacy against controlling infection, with special emphasis on potential roadblocks, and prospects are discussed.