Expanding Our Horizons: AIE Materials in Bacterial Research.

Bacteria share a longstanding and complex relationship with humans, playing a role in protecting gut health and sustaining the ecosystem to cause infectious diseases and antibiotic resistance. Luminogenic materials that share aggregation-induced emission (AIE) characteristics have emerged as a versatile toolbox for bacterial studies through fluorescence visualization. Numerous research efforts highlight the superiority of AIE materials in this field. Recent advances in AIE materials in bacterial studies are categorized into four areas: understanding bacterial interactions, antibacterial strategies, diverse applications, and synergistic applications with bacteria. Initial research focuses on visualizing the unseen bacteria and progresses into developing strategies involving electrostatic interactions, amphiphilic AIE luminogens (AIEgens), and various AIE materials to enhance bacterial affinity. Recent progress in antibacterial strategies includes using photodynamic and photothermal therapies, bacterial toxicity studies, and combined therapies. Diverse applications from environmental disinfection to disease treatment, utilizing AIE materials in antibacterial coatings, bacterial sensors, wound healing materials, etc., are also provided. Finally, synergistic applications combining AIE materials with bacteria to achieve enhanced outcomes are explored. This review summarizes the developmental trend of AIE materials in bacterial studies and is expected to provide future research directions in advancing bacterial methodologies.

Mechanisms of bacterial resistance to environmental silver and antimicrobial strategies for silver: A review.

The good antimicrobial properties of silver make it widely used in food, medicine, and environmental applications. However, the release and accumulation of silver-based antimicrobial agents in the environment is increasing with the extensive use of silver-based antimicrobials, and the prevalence of silver-resistant bacteria is increasing. To prevent the emergence of superbugs, it is necessary to exercise rational and strict control over drug use. The mechanism of bacterial resistance to silver has not been fully elucidated, and this article provides a review of the progress of research on the mechanism of bacterial resistance to silver. The results indicate that bacterial resistance to silver can occur through inducing silver particles aggregation and Ag+ reduction, inhibiting silver contact with and entry into cells, efflux of silver particles and Ag+ in cells, and activation of damage repair mechanisms. We propose that the bacterial mechanism of silver resistance involves a combination of interrelated systems. Finally, we discuss how this information can be used to develop the next generation of silver-based antimicrobials and antimicrobial therapies. And some antimicrobial strategies are proposed such as the "Trojan Horse" - camouflage, using efflux pump inhibitors to reduce silver efflux, working with "minesweeper", immobilization of silver particles.

Nanomaterials-Enabled Physicochemical Antibacterial Therapeutics: Toward the Antibiotic-Free Disinfections.

Bacterial infection continues to be an increasing global health problem with the most widely accepted treatment paradigms restricted to antibiotics. However, the overuse and misuse of antibiotics have triggered multidrug resistance of bacteria, frustrating therapeutic outcomes, and leading to higher mortality rates. Even worse, the tendency of bacteria to form biofilms on living and nonliving surfaces further increases the difficulty in confronting bacteria because the extracellular matrix can act as a robust barrier to prevent the penetration of antibiotics and resist environmental damage. As a result, the inability to eliminate bacteria and biofilms often leads to persistent infection, implant failure, and device damage. Therefore, it is of paramount importance to develop alternative antimicrobial agents while avoiding the generation of bacterial resistance to prevent the large-scale growth of bacterial resistance. In recent years, nano-antibacterial materials have played a vital role in the antibacterial field because of their excellent physical and chemical properties. This review focuses on new physicochemical antibacterial strategies and versatile antibacterial nanomaterials, especially the mechanism and types of 2D antibacterial nanomaterials. In addition, this advanced review provides guidance on the development direction of antibiotic-free disinfections in the antibacterial field in the future.

Amyloid-like protein bridged nano-materials and fabrics for preparing rapid and long lasting antibacterial, UV-resistant and personal thermal management textiles.

Textiles with efficient and long-lasting antibacterial properties have attracted significant attention. However, a single antibacterial model is insufficient to with variable environments and achieve higher antibacterial activity. In this study, lysozyme was used as assistant and stabilizer, and the efficient peeling and functional modification of molybdenum disulfide nanosheets were realized by ultrasonic. Additionally, lysozyme in the presence of reducing agents to form amyloid-like phase-transited lysozyme (PTL) and self-assembling on the wool fabric. Finally, the AgNPs are reduced in situ by PTL and anchored onto the fabric. It has been demonstrated that Ag-MoS2/PTL@wool generates ROS under light irradiation, rapidly converts photothermal heat into generate hyperthermia, and promotes the release of Ag+. The aforementioned "four-in-one" approach resulted in bactericidal rates of 99.996 % (4.4 log, P < 0.0005) and 99.998 % (4.7 log, P < 0.0005) for S.aureus and E.coli, respectively. Even after 50 washing cycles, the inactivation rates remained at 99.813 % and 99.792 % for E.coli and S.aureus, respectively. In the absence of sunlight, AgNPs and PTL continue to provide continuous antibacterial activity. This work emphasizes the importance of amyloid protein in the synthesis and application of high-performance nanomaterials and provides a new direction for the safe and effective application of multiple synergistic antibacterial modes for microbial inactivation.

Reprogramming Targeted-Antibacterial-Plasmids (TAPs) to achieve broad-host range antibacterial activity.

The emergence and spread of antimicrobial resistance results in antibiotic inefficiency against multidrug resistant bacterial strains. Alternative treatment to antibiotics must be investigated to fight bacterial infections and limit this global public health problem. We recently developed an innovative strategy based on mobilizable Targeted-Antibacterial-Plasmids (TAPs) that deliver CRISPR/Cas systems with strain-specific antibacterial activity, using the F plasmid conjugation machinery for transfer into the targeted strains. These TAPs were shown to specifically kill a variety of Enterobacteriaceae strains, including E. coli K12 and the pathogen strains EPEC, Enterobacter cloacae and Citrobacter rodentium. Here, we extend the host-range of TAPs using the RP4 plasmid conjugation system for their mobilization, thus allowing the targeting of E. coli but also phylogenetically distant species, including Salmonella enterica Thyphimurium, Klebsiella pneumoniae, Vibrio cholerae, and Pseudomonas aeruginosa. This work demonstrates the versatility of the TAP strategy and represents a significant step toward the development of non-antibiotic strain-specific antimicrobial treatments.

Flourishing Antibacterial Strategies for Osteomyelitis Therapy.

Osteomyelitis is a destructive disease of bone tissue caused by infection with pathogenic microorganisms. Because of the complex and long-term abnormal conditions, osteomyelitis is one of the refractory diseases in orthopedics. Currently, anti-infective therapy is the primary modality for osteomyelitis therapy in addition to thorough surgical debridement. However, bacterial resistance has gradually reduced the benefits of traditional antibiotics, and the development of advanced antibacterial agents has received growing attention. This review introduces the main targets of antibacterial agents for treating osteomyelitis, including bacterial cell wall, cell membrane, intracellular macromolecules, and bacterial energy metabolism, focuses on their mechanisms, and predicts prospects for clinical applications.

The mud-dwelling clam Meretrix petechialis secretes endogenously synthesized erythromycin.

Although lacking an adaptive immune system and often living in habitats with dense and diverse bacterial populations, marine invertebrates thrive in the presence of potentially challenging microbial pathogens. However, the mechanisms underlying this resistance remain largely unexplored and promise to reveal novel strategies of microbial resistance. Here, we provide evidence that a mud-dwelling clam, Meretrix petechialis, synthesizes, stores, and secretes the antibiotic erythromycin. Liquid chromatography coupled with mass spectrometry, immunocytochemistry, fluorescence in situ hybridization, RNA interference, and enzyme-linked immunosorbent assay revealed that this potent macrolide antimicrobial, thought to be synthesized only by microorganisms, is produced by specific mucus-rich cells beneath the clam's mantle epithelium, which interfaces directly with the bacteria-rich environment. The antibacterial activity was confirmed by bacteriostatic assay. Genetic, ontogenetic, phylogenetic and genomic evidence, including genotypic segregation ratios in a family of full siblings, gene expression in clam larvae, phylogenetic tree, and synteny conservation in the related genome region further revealed that the genes responsible for erythromycin production are of animal origin. The detection of this antibiotic in another clam species showed that the production of this macrolide is not exclusive to M. petechialis and may be a common strategy among marine invertebrates. The finding of erythromycin production by a marine invertebrate offers a striking example of convergent evolution in secondary metabolite synthesis between the animal and bacterial domains. These findings open the possibility of engineering-animal tissues for the localized production of an antibacterial secondary metabolite.

Amphipathic dendritic poly-peptides carrier to deliver antisense oligonucleotides against multi-drug resistant bacteria in vitro and in vivo.

BACKGROUND: Outbreaks of infection due to multidrug-resistant (MDR) bacteria, especially Gram-negative bacteria, have become a global health issue in both hospitals and communities. Antisense oligonucleotides (ASOs) based therapeutics hold a great promise for treating infections caused by MDR bacteria. However, ASOs therapeutics are strangled because of its low cell penetration efficiency caused by the high molecular weight and hydrophilicity. RESULTS: Here, we designed a series of dendritic poly-peptides (DPP1 to DPP12) to encapsulate ASOs to form DSPE-mPEG2000 decorated ASOs/DPP nanoparticles (DP-AD1 to DP-AD12) and observed that amphipathic DP-AD2, 3, 7 or 8 with a positive charge ≥ 8 showed great efficiency to deliver ASOs into bacteria, but only the two histidine residues contained DP-AD7 and DP-AD8 significantly inhibited the bacterial growth and the targeted gene expression of tested bacteria in vitro. DP-AD7anti-acpP remarkably increased the survival rate of septic mice infected by ESBLs-E. coli, exhibiting strong antibacterial effects in vivo. CONCLUSIONS: For the first time, we designed DPP as a potent carrier to deliver ASOs for combating MDR bacteria and demonstrated the essential features, namely, amphipathicity, 8-10 positive charges, and 2 histidine residues, that are required for efficient DPP based delivery, and provide a novel approach for the development and research of the antisense antibacterial strategy.

Prospective antibacterial inhibition of c-type cytochrome synthesis.

Sutherland et al. recently reported the in vitro inhibition of Helicobacter hepaticus cytochrome c (cyt c) synthase, which may inactivate c-type cytochromes in this and in other pathogenic bacteria. Here, I discuss the impact of this work, which identifies this conserved synthase as a potential antibacterial target.

Structure-based design of peptides that trigger Streptococcus pneumoniae cell death.

Toxin-antitoxin (TA) systems regulate key cellular functions in bacteria. Here, we report a unique structure of the Streptococcus pneumoniae HigBA system and a novel antimicrobial agent that activates HigB toxin, which results in mRNA degradation as an antibacterial strategy. In this study, protein structure-based peptides were designed and successfully penetrated the S. pneumoniae cell membrane and exerted bactericidal activity. This result represents the time during which inhibitors triggered S. pneumoniae cell death via the TA system. This discovery is a remarkable milestone in the treatment of antibiotic-resistant S. pneumoniae, and the mechanism of bactericidal activity is completely different from those of current antibiotics. Furthermore, we found that the HigBA complex shows a crossed-scissor interface with two intermolecular ß-sheets at both the N and C termini of the HigA antitoxin. Our biochemical and structural studies provided valuable information regarding the transcriptional regulation mechanisms associated with the structural variability of HigAs. Our in vivo study also revealed the potential catalytic residues of HigB and their functional relationships. An inhibition study with peptides additionally proved that peptide binding may allosterically inhibit HigB activity. Overall, our results provide insights into the molecular basis of HigBA TA systems in S. pneumoniae, which can be applied for the development of new antibacterial strategies. DATABASES: Structural data are available in the PDB database under the accession number 6AF4.

[Research Progress on Artifcial Conduits for Urological Application with Antibacterial Function].

Artificial conduits, including ureteral stents and catheters, are used widely as drainage tools in the urinary system. However, various bacteria in the urine and long duration of insertion can arouse the biofilm formation on the pipeline surface, which calls for effective antibacterial strategy. In this article, the mechanism of Catheter Associated Urinary Tract Infections (CAUTI) is explained from the perspective of etiology. Then, the biofilm formation conditions and the features of urine are analyzed, the antibacterial agents and approaches suitable for ureteral stents and catheters are introduced and their pros and cons are discussed respectively.