Gardnerella vaginalis contributes significantly to bacterial vaginosis, which causes an ecological imbalance in vaginal microbiota and presents with the depletion of Lactobacillus sp. Lactobacillus supplementation was reported to be an approach to treat bacterial vaginosis. We investigated the applicability of three Lactobacillus sp. strains (Lactobacillus delbrueckii DM8909, Lactiplantibacillus plantarum ATCC14917, and Lactiplantibacillus plantarum ZX27) based on their probiotic abilities in vitro. The three candidate Lactobacillus sp. strains for bacterial vaginosis therapy showed distinct properties in auto-aggregation ability, hydrophobicity, adhesion to cervical epithelial cells, and survivability in 0.01% hydrogen peroxide. Lpb. plantarum ZX27 showed a higher yield in producing short-chain fatty acids and lactic acid among the three candidate strains, and all three Lactobacillus sp. strains inhibited the growth and adhesion of G. vaginalis. Furthermore, we discovered that the culture supernatant of Lactobacillus sp. exhibited anti-biofilm activity against G. vaginalis. In particular, the Lpb. plantarum ZX27 supernatant treatment decreased the expression of genes related to virulence factors, adhesion, biofilm formation, metabolism, and antimicrobial resistance in biofilm-forming cells and suspended cells. Moreover, Lactobacillus sp. decreased the upregulated expression of interleukin−8 in HeLa cells induced by G. vaginalis or hydrogen peroxide. These results demonstrate the efficacy of Lactobacillus sp. application for treating bacterial vaginosis by limiting the growth, adhesion, biofilm formation, and virulence properties of G. vaginalis.

Porphyrin derivatives are popular photodynamic therapy (PDT) agents; however, their typical insolubility in water has made it challenging to separate cells of organisms in a liquid water environment. Herein, a novel water-soluble 5,10,15,20-tetrakis(4-methoxyphenyl-3-sulfonatophenyl) porphyrin (TMPPS) was synthesized with 95% yield by modifying the traditional sulfonation route. The reaction of TMPPS with AgNO₃ afforded AgTMPPS an unusual Ag(II) oxidation state (97% yield). The free base and Ag(II) complex were characterized by matrix-assisted laser desorption ionization-mass spectroscopy, and ¹H nuclear magnetic resonance, Fourier-transform infrared, UV-vis, fluorescence, and X-ray photolectron spectroscopies. Upon 460 nm laser irradiation, AgTMPPS generated a large amount of ¹O₂, whereas no ⦁OH was detected. Antibacterial experiments on methicillin-resistant Staphylococcus aureus (MRSA) revealed that the combined action of Ag^Ⅱ ions and PDT could endow AgTMPPS with a 100% bactericidal ratio for highly concentrated MRSA (10⁸ CFU/mL) at a very low dosage (4 μM) under laser irradiation at 360 J/cm². Another PDT response was demonstrated by photocatalytically oxidizing 1,4-dihydronicotinamide adenine dinucleotide to NAD⁺ with AgTMPPS. The structural features of the TMPPS and AgTMPPS molecules were investigated by density functional theory quantum chemical calculations to demonstrate the efficient chemical and photodynamical effects of AgTMPPS for non-invasive antibacterial therapy.

In order to achieve sustained and controlled release of the hydrophobic cargoes, improve the bioavailability, and reduce the side effects of antibiotics, the model drug erythromycin (EM) was used to prepare polycaprolactone-polyethylene glycol (PCL-PEG)/EM micelles. PCL-PEG, a biocompatible and biodegradable amphiphilic polymer, was used as carrier material of micelles to optimize the formulation and preparation process by orthogonal design. The morphology, stability, drug loading, and encapsulation efficiency and the in vitro release behavior of the micelles were investigated. In addition, activity assays of anti-Staphylococcus aureus were performed. The results indicated that PCL-PEG/EM were rod-like micelles with an average particle size of nm and a zeta potential of +19 mV. The average drug loading and encapsulation efficiency were approximately 6.5% and 97.0%, respectively. The micelles were stable in the serum within three days. At the effective concentration of the drug, the formulation indicated no apparent toxicity to the cells. The micelles were able to rapidly enter Staphylococcus aureus (S. aureus) and to provide sustained release cargoes that effectively inhibited S. aureus proliferation. The present study provided a new platform for the rational and effective use of hydrophobic antibiotics to treat infections.

Emerging resistance to colistin in Acinetobacter baumannii is concerning because of the limited therapeutic options for this important clinical pathogen. Given the shortage of new antibiotics, one strategy that has been proven to be therapeutically effective is to overcome antibiotic-resistant pathogens by combining existing antibiotics with another antibiotic or non-antibiotic. This study was designed to investigate the potential synergistic antibacterial activity of amorolfine, a morpholine antifungal drug, in combination with colistin against A. baumannii. In this work, antibiotic susceptibility testing, checkerboard assays, and time-kill curves were used to investigate the synergistic efficacy of colistin combined with amorolfine. The molecular mechanisms of combination therapy were analyzed using fluorometric assays, UV-vis spectroscopy, and molecular docking. Finally, we evaluated the in vivo efficacy of combination therapy against A. baumannii. In brief, the combination therapy showed significant synergistic activity against A. baumannii (FICI = 0.094). In addition, the combination of amorolfine improved the membrane disruption of colistin, and amorolfine exhibited the capacity of binding to DNA. Moreover, in a mouse sepsis model, this combination therapy increased survival compared to colistin monotherapy. Our findings demonstrated that amorolfine serves as a potential colistin adjuvant against Acinetobacter baumannii.

Background: Antibiotic resistance and tolerance pose dual challenges to clinical antibiotic therapy, with tolerance potentially accelerating resistance evolution. LYSC98, a candidate drug that has just received clinical approval in China, has been reported to have bactericidal activity against antibiotic-resistant Staphylococcus aureus. However, its mechanism and activity against antibiotic-resistant bacteria in tolerant state remains unexplored. Objectives: To evaluate the antibacterial activity of LYSC98 against antibiotic-resistant bacteria in different metabolite states, and to elucidate its mechanism of action. Materials and methods: MIC values of antimicrobial agents were determined using broth microdilution. Time–kill assays were used to evaluate the bactericidal effect. SEM and TEM were conducted to visualize the morphological changes. Membrane permeability was determined by propidium iodide. Results: LYSC98 showed potent antibacterial activity against Gram-positive pathogens, with MICs ranging from 0.06 to 2 mg/L. It demonstrated a rapid bactericidal effect against antibiotic-resistant pathogens, irrespective of their growth phase or tolerant state, and conferred an extended post-antibiotic effect. Significantly, LYSC98 displayed a low potential for resistance development. It targeted both bacterial cell wall and membrane, with in vitro membrane assays indicating selective damage to these structures and no observed harm to mammalian cells. Conclusions: LYSC98’s rapid bactericidal activity, selective disruption of bacteria without harming mammalian cells and low propensity for resistance development make it a novel promising candidate for combating chronic, clinically recalcitrant infections.