The preparation of a solid dosage form containing bacteriophages, which meets pharmaceutical requirements and ensures long-term stability of the phage effect, is significant for implementing phage therapy in practice. A commonly used method for processing phages into a solid form is freeze-drying into a so-called freeze-dried cake; however, to date there have been no studies examining the pharmacopeial parameters of freeze-dried tablets with bacteriophages. In this study, we describe the preparation and properties of freeze-dried tablets containing a cocktail of purified pseudomonal bacteriophage DSM 33593 from the genus Pbunavirus and staphylococcal bacteriophage DSM 33473 from the genus Kayvirus (108 PFU/tablet) as the active ingredient. Maltodextrin was used as a tablet filler, and D-mannitol was used as a cryoprotectant. The tablet preparation process resulted in a decrease in phage titer by no more than 1 log PFU/mL. For Pbunavirus, the titer values in tablet and liquid form were comparable. Kayvirus was more stable in tablet form than in liquid form after six months of storage at 25 °C (a decrease of 1.9 ± 0.8 log PFU/mL and 3.8 ± 0.7 log PFU/mL, respectively). The uniformity of mass of single-dose preparations, uniformity of content of single-dose preparations, and their disintegration complied with pharmacopeial requirements. The uniformity of dosage units of the tablets was maintained over three months. A microscopic examination of the internal part of the tablet revealed a heterogeneous structure, which does not affect the required pharmacopeial properties of the tablets. This study highlights the potential of freeze-dried tablets for long-term preservation of the phage effect at room temperature.
- Klíčová slova
- D-mannitol (PubChem CID: 6251), Disodium hydrogen phosphate (PubChem CID: 24203), Dosage form, Drug stability, Freeze-dried tablets, Kayvirus, Magnesium sulfate heptahydrate (PubChem CID: 24843), Maltodextrin (PubChem CID: 68229136), Pbunavirus, Phage therapy, Potassium chloride (PubChem CID: 4873), Potassium dihydrogen phosphate (PubChem CID: 516951), Sodium chloride (PubChem CID: 5234), Sodium deoxycholate (PubChem CID: 23668196), Tris hydrochloride (PubChem CID: 93573), Trisodium citrate (PubChem CID: 6224),
- MeSH
- bakteriofágy MeSH
- fágová terapie metody MeSH
- fágy pseudomonád MeSH
- lyofilizace * MeSH
- mannitol chemie MeSH
- polysacharidy chemie MeSH
- příprava léků metody MeSH
- Pseudomonas aeruginosa * účinky léků virologie MeSH
- stabilita léku MeSH
- stafylokokové bakteriofágy MeSH
- Staphylococcus aureus * účinky léků virologie MeSH
- tablety * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- maltodextrin MeSH Prohlížeč
- mannitol MeSH
- polysacharidy MeSH
- tablety * MeSH
Medical students are exposed to the hospital environment and patients during their studies, increasing the risk of exposure to virulent and antibiotic-resistant isolates of Staphylococcus aureus. The aim of the study is to determine the prevalence of Staphylococcus aureus among medical students who have varying levels of exposure to the hospital environment to provide valuable insights into the risk of colonization and transmission. Nasal swabs and fingerprints were obtained and cultured on a selective medium for staphylococci. The obtained isolates were confirmed as methicillin-sensitive S. aureus (MSSA) or methicillin-resistant (MRSA) using PCR. Antibiotic resistance, the presence of virulence genes including enterotoxin encoding genes, and spa typing were performed. Among pre-clinical students, MSSA was detected on the nose in 45.2% and on the fingerprints in 10.6% of the participants. Among clinical students, MSSA was detected on the nose in 42.0% and on the fingerprints in 25.4%. Only one MRSA isolate was obtained. Genes seg and sei were the most frequently detected in both student groups, with their presence in over 40% of isolates among clinical students. The eta and etb genes were mainly detected from the nose in both student groups. In pre-clinical students, S. aureus carrying eta gene occurred in 6.4% and etb in 8.5%. In clinical students, the occurrence was 5.1% for eta and 8.5% for etb. The tst gene was identified only in the nose and fingerprints of the clinical student group. The most frequently observed resistance was to clindamycin and erythromycin. In total 58 different spa types were identified. High rates of asymptomatic MSSA carriage were observed in both groups of medical students. Detected MSSA strains showed a high degree of genetic variability, with a number of them carrying the virulence and antibiotic resistance genes. Although students do not exhibit increased risk to their patient's, increased hygiene is required in asymptomatic carriage personnel. The overall prevalence of MRSA was low, with a minimal risk of spread.
- Klíčová slova
- Spa type, Staphylococcus aureus, Antibiotic resistance, MRSA, Medical students, Virulence genes,
- MeSH
- antibakteriální látky farmakologie MeSH
- dospělí MeSH
- faktory virulence * genetika MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus genetika izolace a purifikace účinky léků klasifikace MeSH
- mikrobiální testy citlivosti MeSH
- mladý dospělý MeSH
- přenašečství * mikrobiologie epidemiologie MeSH
- prevalence MeSH
- stafylokokové infekce * mikrobiologie epidemiologie MeSH
- Staphylococcus aureus * genetika izolace a purifikace účinky léků klasifikace MeSH
- studenti lékařství * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- faktory virulence * MeSH
Antibiotic-resistant strains of Staphylococcus aureus pose a significant threat in healthcare, demanding urgent therapeutic solutions. Combining bacteriophages with conventional antibiotics, an innovative approach termed phage-antibiotic synergy, presents a promising treatment avenue. However, to enable new treatment strategies, there is a pressing need for methods to assess their efficacy reliably and rapidly. Here, we introduce a novel approach for real-time monitoring of pathogen lysis dynamics employing the piezoelectric quartz crystal microbalance (QCM) with dissipation (QCM-D) technique. The sensor, a QCM chip modified with the bacterium S. aureus RN4220 ΔtarM, was utilized to monitor the activity of the enzyme lysostaphin and the phage P68 as model lytic agents. Unlike conventional QCM solely measuring resonance frequency changes, our study demonstrates that dissipation monitoring enables differentiation of bacterial growth and lysis caused by cell-attached lytic agents. Compared to reference turbidimetry measurements, our results reveal distinct alterations in the growth curve of the bacteria adhered to the sensor, characterized by a delayed lag phase. Furthermore, the dissipation signal analysis facilitated the precise real-time monitoring of phage-mediated lysis. Finally, the QCM-D biosensor was employed to evaluate the synergistic effect of subinhibitory concentrations of the antibiotic amoxicillin with the bacteriophage P68, enabling monitoring of the lysis of P68-resistant wild-type strain S. aureus RN4220. Our findings suggest that this synergy also impedes the formation of bacterial aggregates, the precursors of biofilm formation. Overall, this method brings new insights into phage-antibiotic synergy, underpinning it as a promising strategy against antibiotic-resistant bacterial strains with broad implications for treatment and prevention.
- Klíčová slova
- Staphylococcus aureus, Antimicrobial treatment, Multidrug-resistant bacteria, Phage therapy, Phage-antibiotic synergy, Piezoelectric biosensor,
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriofágy MeSH
- biosenzitivní techniky * metody MeSH
- lysostafin farmakologie MeSH
- mikrorovnovážné techniky křemenného krystalu * MeSH
- Staphylococcus aureus * účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- lysostafin MeSH
Finding effective antibiotics against multi-resistant strains of bacteria has been a challenging race. Linker-Evolved-Group-Optimized-Lipophosphonoxins (LEGO-LPPOs) are small modular synthetic antibacterial compounds targeting the cytoplasmic membrane. Here we focused on understanding the reasons for the variable efficacy of selected LEGO-LPPOs (LEGO-1, LEGO-2, LEGO-3, and LEGO-4) differing in hydrophobic and linker module structure and length. LEGO-1-4 permeabilized cytoplasmic membrane of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, LEGO-1 with the longest linker module being the most effective. Gram-positive bacteria were more sensitive to LEGO-LPPO action compared to Gram-negatives, which was manifested as a delayed membrane permeabilization, higher minimal inhibitory concentration and lower amount of LEGO-LPPO bound to the cells. Outer membrane permeability measurements and time-kill assay showed that presence of the intact outer membrane brought about reduced susceptibility of Gram-negatives. Using liposome leakage and in silico simulations, we showed that membranes with major content of phosphatidylethanolamine were more prone to LEGO-LPPO permeabilization. The proposed mechanism stems from an electrostatic repulsion between highly positively charged LEGO-1 molecules and positively charged amino groups of phosphatidylethanolamine which destabilizes the membrane. Collectively, these data suggest that LEGO-LPPO membrane activity is enhanced by presence of phosphatidylethanolamine but hindered by presence of intact outer membrane.
- MeSH
- antibakteriální látky * farmakologie chemie MeSH
- buněčná membrána metabolismus MeSH
- Escherichia coli metabolismus účinky léků MeSH
- fosfatidylethanolaminy * chemie metabolismus MeSH
- mikrobiální testy citlivosti * MeSH
- permeabilita buněčné membrány účinky léků MeSH
- Staphylococcus aureus účinky léků metabolismus MeSH
- vnější bakteriální membrána metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- fosfatidylethanolaminy * MeSH
- phosphatidylethanolamine MeSH Prohlížeč
Public transport represents a potential site for the transmission of resistant pathogens due to the rapid movement of large numbers of people. This study aimed to investigate the bacterial contamination of frequently touched surfaces in the public transport system operating in the proximity of the biggest Czech hospital during the coronavirus pandemic despite extensive cleaning and disinfection efforts. In June and September 2020, samples from the metro trains, ground transport and stationary objects were collected, enriched and cultured. The antimicrobial susceptibility was tested by broth microdilution. Staphylococcus aureus isolates exhibiting inconclusive results of vancomycin susceptibility testing were retested by broth macrodilution and subjected to whole genome sequencing. All S. aureus isolates were tested for vancomycin heteroresistance (hVISA). A total of 513/542 (94.6 %) samples were culture-positive with higher frequency in September (p = 0.004). S. aureus was the most frequent opportunistic bacterial pathogen found (3.7 %, 20/542) followed by Enterobacterales spp. (1.8 %, 10/542). No methicillin-resistant S. aureus (MRSA), extended-spectrum beta-lactamase producers (ESBL) or carbapenemase-producing bacteria were detected. Resistance to clinically relevant drugs was rare except for resistance to ampicillin (67 %, 8/12), cefuroxime (42 %, 5/12) in Enterobacterales and chloramphenicol (90 %, 18/20), penicillin (45 %, 9/20), and erythromycin (20 %, 4/20) in S. aureus. One S. aureus isolate was shown to be resistant to vancomycin (8 mg/L) by forming large visible cell aggregates. Population analysis profile-area under the curve ratio (PAP-AUC) testing did not confirm the hVISA phenotype, but mutations in the hVISA phenotype-related gene vraR and other genes related to cell wall synthesis (fmtB) and intercellular adhesion (sasC) were found. Our study shows that in the COVID-19 pandemic, despite the intensive use of disinfectants, public transport was a source of opportunistic bacterial pathogens including S. aureus with unusual vancomycin resistance phenotype that could be easily missed by standard susceptibility testing.
- Klíčová slova
- Antimicrobial resistance, Environmental contamination, Public transport, Staphylococcus aureus, Vancomycin resistance, Whole genome sequencing,
- MeSH
- antibakteriální látky * farmakologie MeSH
- COVID-19 * MeSH
- doprava MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- pandemie MeSH
- rezistence na vankomycin MeSH
- SARS-CoV-2 * MeSH
- Staphylococcus aureus * účinky léků genetika MeSH
- vankomycin * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- antibakteriální látky * MeSH
- vankomycin * MeSH
Two In(III) - pyridinecarboxylates ([In(Pic)2(NO3)(H2O)] (InPic; HPic = picolinic acid), [In(HDpic)(Dpic)(H2O)2]·5H2O (InDpic; H2Dpic = dipicolinic acid), have been synthesized by one-step procedure. The complexes composition was confirmed by physicochemical analyses and X-ray diffraction confirmed molecular structure of both complexes. Moreover, complex species speciation was described in both systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [In(Pic)]2+ (logβ011 = 6.94(4)), [In(Pic)2]+ (logβ021 = 11.98(9)), [In(Dpic)]+ (logβ011 = 10.42(6)), [In(Dpic)2]- (logβ021 = 17.58(7)) and [In(Dpic)2(OH)]2- (logβ-121 = 10.18(6)). To confirm the complexes stability in 1 % DMSO, 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial and anticancer assays indicate a more significant sensitivity of S. aureus bacteria and MDA-MB-231 cancer cells to the InPic complex (IC50 = 25 and 340.7 μM) than to the InDpic (IC50 = 50 and 975.4 μM). The interaction and binding mechanism of picolinic/dipicolinic acid and their indium(III) complexes with HSA (human serum albumin) were studied using fluorescence and CD spectroscopy. The results confirmed that the studied compounds had bound successfully to HSA, and the binding parameters and constants (KSV, Kq, Kb) were calculated together with the number of binding sites. The binding forces were identified based on calculated thermodynamic parameters (ΔG, ΔH, ΔS). Synchronous spectra were used to study the microenvironment of Tyr and Trp residues and displacement assays revealed that site I was the preferred binding site. After binding, conformational changes were found to have occurred in the HSA molecule and the % α-helical content had decreased.
- Klíčová slova
- Anticancer, Antimicrobial, HSA binding, In(III) complexes, Potentiometry, Pyridinecarboxylates, Stability,
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- antitumorózní látky chemie farmakologie chemická syntéza MeSH
- komplexní sloučeniny chemie chemická syntéza MeSH
- kyseliny pikolinové * chemie MeSH
- lidé MeSH
- lidský sérový albumin * chemie metabolismus MeSH
- nádorové buněčné linie MeSH
- Staphylococcus aureus účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- antitumorózní látky MeSH
- dipicolinic acid MeSH Prohlížeč
- komplexní sloučeniny MeSH
- kyseliny pikolinové * MeSH
- lidský sérový albumin * MeSH
- picolinic acid MeSH Prohlížeč
Biomaterial-associated infections pose severe challenges in modern medicine. Previously, we reported that polyanionic DNA surface coatings repel bacterial adhesion and support osteoblast-like cell attachment in monoculture experiments, candidate for orthopaedic implant coatings. However, monocultures lack the influence of bacteria or bacterial toxins on osteoblast-like cell adhesion to biomaterial surfaces. In this study, co-culture of staphylococcus (S. epidermidis and S. aureus) and SaOS-2 osteosarcoma cells was studied on chitosan-DNA polyelectrolyte multilayer coated glass based on the concept of `the race for the surface`. Staphylococcus was first deposited onto the surface in a microfluidic chamber to mimic peri-operative contamination, and subsequently, SaOS-2 cells were seeded. Both staphylococcus and SaOS-2 cells were cultured together on the surfaces for 24 h under flow. The presence of S. epidermidis decreased SaOS-2 cell number on all surfaces after 24 h. However, the cells that adhered spread equally well in the presence of low virulent S. epidermidis. However, highly virulent S. aureus induced cell death of all adherent SaOS-2 cells on chitosan-DNA multilayer coated glass, a worse outcome than on uncoated glass. The outcome of our co-culture study highlights the limitations of monoculture models. It demonstrates the need for in vitro co-culture assays to meaningfully bridge the gap in lab testing of biomaterials and their clinical evaluations where bacterial infection can occur. The relative failure of cell-adhesive and bacteria-repelling DNA coatings in co-cultures also suggests the need to incorporate bactericidal in addition to non-adhesive functions to protect competitive cell spreading over a long period.
- Klíčová slova
- Biofilms, Biomaterial-associated infections, Co-culture, Coatings, DNA polyelectrolyte, Flow, Multilayer, Osteoblasts, Pathogens, Race for the surface, Staphylococcus,
- MeSH
- bakteriální adheze účinky léků MeSH
- biokompatibilní potahované materiály chemie farmakologie MeSH
- buněčná adheze účinky léků MeSH
- chitosan chemie farmakologie MeSH
- DNA * chemie MeSH
- kokultivační techniky MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- osteoblasty * účinky léků cytologie MeSH
- polyelektrolyty chemie farmakologie MeSH
- povrchové vlastnosti * MeSH
- Staphylococcus aureus * účinky léků MeSH
- Staphylococcus epidermidis * účinky léků fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biokompatibilní potahované materiály MeSH
- chitosan MeSH
- DNA * MeSH
- polyelektrolyty MeSH
Agrimonia eupatoria L. (AE) has a rich tradition of use in wound healing improvement across various cultures worldwide. In previous studies, we revealed that Agrimonia eupatoria L. water extract (AE) possesses a rich polyphenolic composition, displaying remarkable antioxidant properties. Our investigations also demonstrated that lipophosphonoxin (LPPO) exhibited antibacterial efficacy in vitro while preserving the proliferation and differentiation of fibroblasts and keratinocytes. Building upon our prior findings, in this study, we intended to examine whether a combination of AE and LPPO could enhance skin wound healing while retaining antibacterial attributes. The antibacterial activity of AE/LPPO against Staphylococcus aureus was evaluated, alongside its effects on fibroblast-to-myofibroblast transition, the formation of extracellular matrix (ECM), and endothelial cells and keratinocyte proliferation/phenotype. We also investigated AE/LPPO's impact on TGF-β1 and VEGF-A signaling in keratinocytes/fibroblasts and endothelial cells, respectively. Additionally, wound healing progression in rats was examined through macroscopic observation and histological analysis. Our results indicate that AE/LPPO promotes myofibroblast-like phenotypic changes and augments ECM deposition. Clinically relevant, the AE/LPPO did not disrupt TGF-β1 and VEGF-A signaling and accelerated wound closure in rats. Notably, while AE and LPPO individually exhibited antibacterial activity, their combination did not lead to synergism, rather decreasing antibacterial activity, warranting further examination. These findings underscore substantial wound healing improvement facilitated by AE/LPPO, requiring further exploration in animal models closer to human physiology.
- Klíčová slova
- extracellular matrix, phytotherapy, regeneration, repair, skin tissue,
- MeSH
- Agrimonia * chemie MeSH
- antibakteriální látky * farmakologie chemie MeSH
- fibroblasty účinky léků metabolismus MeSH
- hojení ran * účinky léků MeSH
- keratinocyty účinky léků MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- potkani Sprague-Dawley MeSH
- proliferace buněk účinky léků MeSH
- rostlinné extrakty * farmakologie chemie MeSH
- Staphylococcus aureus * účinky léků MeSH
- transformující růstový faktor beta1 metabolismus MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- rostlinné extrakty * MeSH
- transformující růstový faktor beta1 MeSH
- vaskulární endoteliální růstový faktor A MeSH
Biofilm formation by the pathogenic bacteria generates a serious threat to the public health as it can increase the virulence potential, resistance to drugs, and escape from the host immune response mechanisms. Among the environmental factors that influence the biofilm formation, there are only limited reports available on the role of antimicrobial agents. During the antimicrobial drug administration or application for any purpose, the microbial population can expect to get exposed to the sub-minimum inhibitory concentration (sub-MIC) of the drug which will have an unprecedented impact on microbial responses. Hence, the study has been conducted to investigate the effects of sub-MIC levels of zinc oxide nanoparticles (ZnO NPs) on the biofilm formation of Klebsiella pneumoniae and Staphylococcus aureus. Here, the selected bacteria were primarily screened for the biofilm formation by using the Congo red agar method, and their susceptibility to ZnO NPs was also evaluated. Quantitative difference in biofilm formation by the selected organisms in the presence of ZnO NPs at the sub-MIC level was further carried out by using the microtiter plate-crystal violet assay. Further, the samples were subjected to atomic force microscopy (AFM) analysis to evaluate the properties and pattern of the biofilm modulated under the experimental conditions used. From these, the organisms treated with sub-MIC levels of ZnO NPs were found to have enhanced biofilm formation when compared with the untreated sample. Also, no microbial growth could be observed for the samples treated with the minimum inhibitory concentration (MIC) of ZnO NPs. The results observed in the study provide key insights into the impact of nanomaterials on clinically important microorganisms which demands critical thinking on the antimicrobial use of nanomaterials.
- Klíčová slova
- Klebsiella pneumoniae, Staphylococcus aureus, Antimicrobial agents, Biofilm modulation, Sub-MIC, Zinc oxide nanoparticles,
- MeSH
- antibakteriální látky * farmakologie MeSH
- biofilmy * účinky léků růst a vývoj MeSH
- Klebsiella pneumoniae * účinky léků fyziologie růst a vývoj MeSH
- kovové nanočástice chemie MeSH
- mikrobiální testy citlivosti * MeSH
- mikroskopie atomárních sil MeSH
- nanočástice chemie MeSH
- oxid zinečnatý * farmakologie chemie MeSH
- Staphylococcus aureus * účinky léků fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- oxid zinečnatý * MeSH
Nanostructured materials with antibacterial activity face the same threat as conventional antibiotics - bacterial resistance, which reduces their effectiveness. However, unlike antibiotics, research into the emergence and mechanisms of bacterial resistance to antibacterial nanomaterials is still in its early stages. Here we show how Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria develop resistance to silver nanoparticles, resulting in an increase in the minimum inhibitory concentration from 1.69 mg/L for S. aureus and 3.38 mg/L for E. coli to 54 mg/L with repeated exposure over 12 and 6 cultivation steps, respectively. The mechanism of resistance is the same for both types of bacteria and involves the aggregation of silver nanoparticles leading to the formation of black precipitates. However, the way in which Gram-positive and Gram-negative bacteria induce aggregation of silver nanoparticles is completely different. Chemical analysis of the surface of the silver precipitates shows that aggregation is triggered by flagellin production in E. coli and by bacterial biofilm formation in S. aureus. However, resistance in both types of bacteria can be overcome by using pomegranate rind extract, which inhibits both flagellin and biofilm production, or by stabilizing the silver nanoparticles by covalently binding them to a composite material containing graphene sheets, which protects the silver nanoparticles from aggregation induced by the bacterial biofilm produced by S. aureus. This research improves the understanding of bacterial resistance mechanisms to nanostructured materials, which differ from resistance mechanisms to conventional antibiotics, and provides potential strategies to combat bacterial resistance and develop more effective antimicrobial treatments.
- MeSH
- antibakteriální látky * farmakologie chemie MeSH
- bakteriální léková rezistence * účinky léků MeSH
- biofilmy účinky léků růst a vývoj MeSH
- Escherichia coli * účinky léků MeSH
- kovové nanočástice * chemie MeSH
- mikrobiální testy citlivosti * MeSH
- Staphylococcus aureus * účinky léků MeSH
- stříbro * farmakologie chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- stříbro * MeSH