Articles in E-pub version are posted online ahead of regular printed publication.
Two novel bacterial species, designated as CJ85T and CJ88T, were isolated from the agricultural soil and the Han River, South Korea, respectively. Cells of both strains were Gram-staining-positive, short rod-shaped, non-motile, and yellow-pigmented. Strain CJ85T exhibited optimal growth in tryptic soy broth at 37°C and pH 7.0 in the absence of NaCl. Strain CJ88T showed optimal growth in lysogeny broth at 30°C and pH 7.0 in the absence of NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CJ85T belonged to the genus Paramicrobacterium, showing the highest sequence similarity to Paramicrobacterium fandaimingii HY82T (97.6%). Strain CJ88T was assigned to the genus Microbacterium, with the highest sequence similarity to Microbacterium azadirachtae DSM 23848T (98.5%). The DNA G + C content was 64.8% for strain CJ85T and 70.5% for strain CJ88T. The genome-based analyses, including phylogenomic tree, digital DNA-DNA hybridization, and average nucleotide identity, clearly indicated that these strains represent novel species within their respective genera. The major fatty acids of both strains were anteiso-C15:0, anteiso-C17:0, and iso-C16:0. Based on the polyphasic taxonomy study, strains CJ85T and CJ88T represent novel species of the genera Paramicrobacterium and Microbacterium, respectively, for which names Paramicrobacterium salitolerans sp. nov. and Microbacterium fluminis sp. nov. are proposed. The type strains CJ85T (= KACC 23064T = JCM 36217T) and CJ88T (= KACC 24080T = JCM 38050T).
Antimicrobial resistance (AMR) poses an ongoing threat to global health, with the number of deaths directly attributable to AMR projected to rise to 8 million. One of the main reasons for the current crisis is the depletion of antibiotic candidates in clinical pipelines. To address this, more preclinical candidates must be advanced into development. However, the scientific challenges and limited economic incentives associated with antibiotic research have further aggravated the situation. Antibiotic hybrids, which combine two antibiotics with different modes of action, have emerged as a promising strategy to overcome AMR and are already being developed for clinical use. This approach takes advantage of the strong selective pressure exerted when two bactericidal agents act simultaneously. Importantly, because hybrids are administered as a single chemical entity, they may offer advantages over conventional combination therapies, such as simplified pharmacokinetics and dosing. Furthermore, since clinically validated antibiotics are used as the building blocks of hybrids, this strategy provides an efficient platform for generating new lead compounds. Recently, the concept of antibiotic hybrids has expanded beyond antibiotic–antibiotic conjugates to include the attachment of functional molecules designed to mitigate the disadvantages of the parent antibiotics. In this review, we summarize the definition of antibiotic hybrids, highlight representative compounds that have entered clinical evaluation, and discuss recent advances in their development.
Ribosomes are essential macromolecular machines that facilitate protein synthesis and have long been recognized as effective targets for antimicrobial agents. While structural differences between prokaryotic and eukaryotic ribosomes form the basis for selective antibiotics against bacteria, similar approaches for developing antifungal agents targeting ribosomes have remained limited due to the high sequence and structural conservation with human ribosomes. However, emerging insights into ribosome homeostasis, including ribosome biogenesis, turnover, and hibernation, have uncovered a set of ribosome-associated proteins whose function is critical yet display greater sequence divergence from their human counterparts. These observations suggest that these regulatory components may represent viable antifungal targets by disrupting fungal proteostasis. The present review aims to explore this developing concept by examining ribosome-associated factors and considering whether short ribosomal protein-derived peptides may eventually serve as druggable molecules for selectively modulating these pathways in fungal pathogens.
Protein quality control systems are increasingly recognized as a critical determinant of bacterial survival and antibiotic tolerance. Conventional antibiotics predominantly target nucleic acids, protein synthesis, or cell wall synthesis, yet bacterial adaptation and resistance emergence remain major challenges. Targeting the bacterial protein quality control machineries including molecular chaperones and proteases offers a promising strategy to overcome these limitations. Recent advances include small molecules and adaptor/degron mimetics that modulate the activities of chaperones and proteases, aggregation-prone peptides (APPs) that induce proteotoxic stress, and bacterial PROTAC (BacPROTAC) strategies that redirect endogenous proteases. Notably, persister and viable-but-non-culturable (VBNC) cells, which tolerate conventional antibiotics, remain susceptible to proteostasis-targeted approaches, thereby enabling killing in both actively dividing and dormant populations. Furthermore, synergistic strategies combining chaperone inhibition or protease activation with conventional antibiotics enhance bactericidal efficacy, suggesting a potential avenue to mitigate antimicrobial resistance. This review summarizes the mechanistic basis, recent developments, and translational potential of proteostasis-centered antibacterial strategies.
The escalating threat of antimicrobial resistance has renewed global interest in peptide-based antibiotics as adaptable and effective alternatives to conventional small molecules. Peptides possess diverse mechanisms of action, high target specificity, and structural flexibility, which collectively limit the emergence of resistance. This review outlines recent advances spanning the discovery, optimization, and application of peptide antibiotics, from their biological origins and structural classifications to emerging strategies involving artificial intelligence, synthetic biology, and modern delivery technologies. Peptide antibiotics can be categorized by origin as natural, semi-synthetic, or fully synthetic, and further organized by structural class such as α-helical, β-sheet, cyclic, and extended forms. They are also grouped by function into membrane-targeted and non-membrane-targeted types. These classification schemes are not only descriptive but also critical for understanding the therapeutic potential of peptides, as each category presents distinct advantages and engineering challenges that influence stability, specificity, and overall clinical performance. Advances in artificial intelligence, synthetic biology, and continuous manufacturing are reshaping how peptide drugs are designed and produced, while innovations in drug delivery systems are addressing critical issues of stability and bioavailability. Together, these developments are laying the foundation for a new generation of peptide-based therapeutics capable of meeting the evolving challenges of antimicrobial resistance.