OBJECTIVE: To explore the mechanism of antibiotic delivery system targeting bacterial biofilm with linezolid (LZD) based on ε-poly- L-lysine (ε-PLL) and cyclodextrin (CD) (ε-PLL-CD-LZD), aiming to enhance antibiotic bioavailability, effectively penetrate and disrupt biofilm structures, and thereby improve the treatment of bone and joint infections. METHODS: ε-PLL-CD-LZD was synthesized via chemical methods. The grafting rate of CD was characterized using nuclear magnetic resonance. In vitro biocompatibility was evaluated through live/dead cell staining after co-culturing with mouse embryonic osteoblast precursor cells (MC3T3-E1), human umbilical vein endothelial cells, and mouse embryonic fibroblast cells (3T3-L1). The biofilm-enrichment capacity of ε-PLL-CD-LZD was assessed using Staphylococcus aureus biofilms through enrichment studies. Its biofilm eradication efficacy was investigated via minimum inhibitory concentration (MIC) determination, scanning electron microscopy, and live/dead bacterial staining. A bone and joint infection model in male Sprague-Dawley rats was established to validate the antibacterial effects of ε-PLL-CD-LZD. RESULTS: In ε-PLL-CD-LZD, the average grafting rate of CD reached 9.88%. The cell viability exceeded 90% after co-culturing with three types cells. The strong biofilm enrichment capability was observed with a MIC of 2 mg/L. Scanning electron microscopy observations revealed the effective disruption of biofilm structure, indicating potent biofilm eradication capacity. In vivo rat experiments demonstrated that ε-PLL-CD-LZD significantly reduced bacterial load and infection positivity rate at the lesion site ( P<0.05). CONCLUSION The ε-PLL-CD antibiotic delivery system provides a treatment strategy for bone and joint infections with high clinical translational significance. By effectively enhancing antibiotic bioavailability, penetrating, and disrupting biofilms, it demonstrated significant anti-infection effects in animal models.
Biofilms/drug effects* ; Animals ; Anti-Bacterial Agents/pharmacology* ; Polylysine/chemistry* ; Cyclodextrins/administration & dosage* ; Humans ; Linezolid/pharmacology* ; Staphylococcus aureus/physiology* ; Rats, Sprague-Dawley ; Mice ; Rats ; Male ; Drug Delivery Systems ; Staphylococcal Infections/drug therapy* ; Microbial Sensitivity Tests ; Human Umbilical Vein Endothelial Cells ; Osteoblasts/cytology*

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

Objective:Multi-drug resistant bacterial infection（MRSA） complications occurring in cochlear implant recipients is rare and of serious consequence. This paper aimed to summarize the treatment experience of a patient with MRSA infection after cochlear implantation. A patient with nasopharyngeal malignant tumor after radiotherapy developed to severe sensorineural deafness. She suffered MRSA infection nine days after cochlear implantation. Since the wound failed to heal after weeks of topical and systemic sensitive antibiotic therapy, the patient underwent surgery for wound debridement. The stimulator-receiver and the electrode of the implant was removed, negative pressure wound therapy was applied, and systemic anti-infection treatment with sensitive antibiotics for weeks, the patients recovered and was discharged from hospital 69 days after infection.
Humans ; Cochlear Implantation/adverse effects* ; Female ; Drug Resistance, Multiple, Bacterial ; Staphylococcal Infections/therapy* ; Methicillin-Resistant Staphylococcus aureus ; Cochlear Implants ; Anti-Bacterial Agents/therapeutic use* ; Postoperative Complications ; Middle Aged

Chronic rhinosinusitis with nasal polyps（CRSwNP） represents a prevalent inflammatory disorder, which is often accompanied by nasal congestion, mucopurulent discharge, olfactory dysfunction, dizziness, and headache. Staphylococcus aureus（SA）, a predominant opportunistic pathogen within the sinonasal microenvironment, has been implicated in modulating the pathogenesis and progression of CRSwNP through multifaceted mechanisms. The physiological activities of SA-dependent quorum-sensing system and biofilm in the nasal microenvironment, including interactions with host, fungi, viruses, and other bacteria, as well as the effects of important superantigens secreted by SA on the microenvironment and immune barrier, are briefly reviewed in this article. These insights provide theoretical foundations for elucidating CRSwNP mechanisms and advancing clinical therapeutic strategies.
Humans ; Sinusitis/microbiology* ; Nasal Polyps/microbiology* ; Staphylococcus aureus ; Chronic Disease ; Rhinitis/microbiology* ; Staphylococcal Infections/microbiology* ; Quorum Sensing ; Biofilms ; Rhinosinusitis

OBJECTIVES: To evaluate the photothermal and antibacterial activities of polydopamine-modified phycocyanin nanoparticles (PDA@PC NPs) and their capacity for promoting wound healing. METHODS: PDA@PC NPs were synthesized from phycocyanin (C-PC) and dopamine hydrochloride using a one-pot method. The photothermal activity of the nanoparticles was assessed in vitro by 808 nm laser irradiation, their biocompatibility was evaluated using CCK-8 assay, and their photothermal antibacterial activity by plate colony counting. In adult male BALB/c mice, two symmetrical full-thickness skin wounds (1.0 cm ×1.0 cm) were created on both sides of the spine, and 200 μL of Staphylococcus aureus suspension was inoculated into the wounds. The mice were divided into control group, PDA@PC NPs group, and PDA@PC NPs with laser irradiation group, and wound healing rates and histomorphological changes in the wound tissues were evaluated on days 0, 7 and 14 after modeling. RESULTS: The synthesized PDA@PC NPs exhibited no obvious cytotoxicity up to a concentration of 500 μg/mL and showed strong photothermal and antibacterial activities in response to 808 nm laser irradiation. In the mouse models, the size of the infected skin wounds showed substantial reduction at 7 and 14 days in PDA@PC NPs group and PDA@PC NPs with laser irradiation group, and the mean wound healing rate was faster in the latter group. HE staining and Masson's trichrome staining revealed extensive granulation tissue formation and collagen deposition on the wound surfaces in both of the treatment groups, and these changes were more obvious in the PDA@PC NPs with laser irradiation group. CONCLUSIONS PDA@PC NPs possess excellent photothermal and antibacterial activities and can effectively promote wound healing in mice.
Animals ; Indoles/chemistry* ; Wound Healing/drug effects* ; Mice ; Mice, Inbred BALB C ; Male ; Nanoparticles ; Polymers/chemistry* ; Phycocyanin/chemistry* ; Skin/injuries* ; Staphylococcus aureus/drug effects* ; Anti-Bacterial Agents/pharmacology*

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

BACKGROUND AND OBJECTIVE

The emergence of antimicrobial resistance (AMR) poses a significant global health threat, with developing countries such as the Philippines facing particularly severe impacts due to resource limitations. The most affected by AMR is Healthcare Acquired Infections (HAIs), including Catheter-Related Bloodstream Infections (CRBSIs). These are commonly associated with biofilm-forming bacteria like Staphylococcus epidermidis, which complicates treatment due to antibiotic resistance. The Philippine variety of Psidium guajava, a folklorically used medicinal plant, has shown potential antimicrobial properties that could offer a new avenue for combating resistant pathogens.

This study evaluated the antibacterial and antibiofilm efficacy of crude Psidium guajava ethanolic leaf extracts (PGELE) against biofilm-forming S. epidermidis (ATCC 12228). PGELE was tested at five concentrations (ranging from 312.5 µg/mL to 10,000 µg/mL) using two-fold serial dilution to determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) using agar dilution count method. For the Minimum Biofilm Inhibitory Concentration (MBIC) and Minimum Biofilm Eradication Concentration (MBEC), crude PGELE was tested at 0.25 x MIC, 0.5 x MIC, MIC, 2 x MIC and 4 x MIC.

The MIC for PGELE against S. epidermidis was determined to be 2500 µg/mL, and the MBC was 5000 µg/mL, indicating that PGELE exhibits bactericidal activity. In biofilm assays, PGELE demonstrated strong antibiofilm activity at concentrations as low as 625 µg/ mL, inhibiting biofilm formation by more than 50%. However, PGELE did not eradicate preformed biofilms, as indicated by the MBEC results at concentrations ranging from 625 µg/mL to 10,000 µg/mL.

Psidium guajava ethanolic leaf extracts exhibit antibacterial and antibiofilm activities against S. epidermidis, particularly in preventing biofilm formation. These findings suggest that PGELE could be developed as an effective natural antimicrobial agent for use in healthcare settings to prevent CRBSIs and other infections caused by biofilm-forming pathogens. Further research and development are warranted to explore the potential of PGELE for antimicrobial drug development.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

OBJECTIVES: Calcium silicate (CSO) is modified to give it photothermal antibacterial properties. Its application potential in tooth mineralization and oral antibacterial is evaluated. METHODS: Based on defect-engineering modification strategy, a series of CSO-T samples (CSO-300, CSO-400, CSO-500, CSO-600) was obtained by introducing oxygen vacancy into CSO through thermal reduction using sodium borohydride. The samples were tested using scanning electron microscopy (SEM), X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet near-infrared absorption spectroscopy, and infrared thermography. The powder samples with the best photothermal performance and the most suitable material concentration (CSO-500, 500 μg/mL) were selected for subsequent experiments. High resolution transmission electron microscopy was used to analyze the microstructure and morphology of the sample, and MTT assay and Calcein AM/PI live/dead cell staining were used to evaluate the toxicity and compatibility of the sample to human oral keratinocytes. Escherichia coli and Staphylococcus aureus were selected for photothermal antibacterial experiments to evaluate their in vitro antibacterial performance. SEM, energy dispersive spectrometer, and micro Vickers hardness tester were used to evaluate the ability of materials to induce in vitro remineralization of detached teeth. RESULTS: Oxygen vacancies changed the crystal type and lattice spacing of CaSiO₃, broadened the light-absorption range, and gave it a good photothermal conversion ability in response to near infrared. Invitro experiments showed that the modified CaSiO₃ could promote the formation of hydroxyapatite on the tooth surface, thereby promoting the remineralization of teeth and improving the teeth hardness. Moreover, it had photothermal antibacterial properties and no cytotoxicity. CONCLUSIONS Defect-modified black calcium silicate has multiple functions, such as promoting tooth remineralization and photothermal bacteriostatic. When combined with the infrared luminescent toothbrush, it can simply and effectively treat tooth enamel erosion and oral bacteriostatic diseases caused by the excessive consumption of carbonated beverages and other daily bad living habits. This combination is expected to achieve the synergic treatment effect of tooth remineralization and oral bacteriostatic through daily cleaning is expected.
Calcium Compounds/pharmacology* ; Silicates/pharmacology* ; Humans ; Staphylococcus aureus/drug effects* ; Tooth Remineralization ; Escherichia coli/drug effects* ; Anti-Bacterial Agents/pharmacology* ; Keratinocytes/drug effects* ; Microscopy, Electron, Scanning

One of the technical bottlenecks limiting the high yield of 1,4-butanediamine is the insufficient tolerance of strains to 1,4-butanediamine. Enhancing the tolerance of strains to 1,4-butanediamine is therefore a primary challenge that needs to be addressed for the construction of strains with high yields of 1,4-butanediamine. Staphylococcus pasteuri 326180 exhibits exceptional tolerance to high-concentration 1,4-butanediamine, serving as both an ideal model for studying the mechanism underlying the 1,4-butanediamine tolerance and a novel host for constructing strains capable of efficiently producing 1,4-butanediamine. However, for both the research on the tolerance mechanism and the modification of chassis strains, gene editing of S. pasteuri needs to be carried out at the molecular level. The research objective of this paper is to establish a genetic manipulation system for S. pasteuri, laying foundation for subsequent studies on tolerance mechanism and the modification of chassis strains. This study systematically optimized the electroporation conditions, including key parameters such as the growth phase of cells, electric field strength, electroporation buffer, and recovery medium, successfully establishing an electroporation method for S. pasteuri. Additionally, we constructed the gene editing plasmid pCpfOA by replacing the resistance expression cassette, optimized the selection markers for gene editing, and finally established a CRISPR/Cpf1-based gene editing technology for S. pasteuri, achieving an editing efficiency of 90%. The genetic manipulation system of S. pasteuri established in this study provides technical support for research into the tolerance mechanism of this bacterium and the genetic modification of chassis strains.
Staphylococcus/drug effects* ; Gene Editing/methods* ; Electroporation/methods* ; Plasmids/genetics* ; CRISPR-Cas Systems ; Genetic Engineering/methods*