Gram-positive bacteria are responsible for a wide range of infections in humans. In most Gram-positive bacteria, sortase A plays a significant role in attaching virulence factors to the bacteria's cell wall. These cell surface proteins play a significant role in virulence and pathogenesis. Even though antibiotics are available to treat these infections, there is a continuous search for an alternative strategy due to an increase in antibiotic resistance. Thus, using anti-sortase drugs to combat these bacterial infections may be a promising approach. Here, we describe a method for targeting Gram-positive bacterial infection by combining curcumin and trans-chalcone as sortase A inhibitors. We have used curcumin and trans-chalcone alone and in combination as a sortase A inhibitor. We have seen ~78%, ~43%, and ~94% inhibition when treated with curcumin, trans-chalcone, and a combination of both compounds, respectively. The compounds have also shown a significant effect on biofilm formation, IgG binding, protein A recruitment, and IgG deposition. We discovered that combining curcumin and trans-chalcone is more effective against Gram-positive bacteria than either compound alone. The present work demonstrated that a combination of these natural compounds could be used as an antivirulence therapy against Gram-positive bacterial infection.

• MeSH
• aminoacyltransferasy * antagonisté a inhibitory   metabolismus   MeSH
• antibakteriální látky * farmakologie   chemie   MeSH
• bakteriální proteiny * metabolismus   antagonisté a inhibitory   MeSH
• biofilmy * účinky léků   MeSH
• chalkon * farmakologie   chemie   MeSH
• cysteinové endopeptidasy * metabolismus   MeSH
• faktory virulence metabolismus   MeSH
• grampozitivní bakteriální infekce farmakoterapie   mikrobiologie   MeSH
• grampozitivní bakterie účinky léků   MeSH
• kurkumin * farmakologie   chemie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• virulence účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Several natural antimicrobial peptides (AMPs), including the novel semisynthetic lipoglycopeptide antibiotics telavancin, dalbavancin, and oritavancin, have been approved for clinical use to address the growing problem of multiple antibiotic-resistant Gram-positive bacterial infections. Nevertheless, the efficacy of these antibiotics has already been compromised. The SARS-CoV-2 pandemic led to the increased clinical use of all antibiotics, further promoting the development of bacterial resistance. Therefore, it is critical to gain a deeper understanding of the role of resistance mechanisms to minimize the consequential risks of long-term antibiotic use and misuse. Here, we summarize for the first time the current knowledge of resistance mechanisms that have been shown to cause resistance to clinically used AMPs, with particular focus on membrane proteins that have been reported to interfere with the activity of AMPs by affecting the binding of AMPs to bacteria.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• antimikrobiální peptidy MeSH
• COVID-19 * MeSH
• grampozitivní bakteriální infekce * farmakoterapie   metabolismus   mikrobiologie   MeSH
• lidé MeSH
• membránové proteiny MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The study aimed to identify colonized patients as a possible source of eventual VRE (vancomycin-resistant enterococci) infection from stool samples positive for glutamate dehydrogenase antigen, as well as for Clostridioides difficile toxins A and B. The study was carried out from 7/2020 to 9/2021. Stool samples were grown in a brain heart infusion medium with a gram-positive non-spore-forming bacteria supplement under aerobic conditions. The samples for VRE identification were grown on CHROMID® VRE agar, and the MICs for vancomycin and teicoplanin were also estimated. The presence of the vanA/vanB genes was tested using the PCR method. The total number of 113 stool samples positive for Clostridioides difficile toxins was analyzed. Of these samples, 44 isolates with VRE characters were identified. The most prevalent isolates in our set of isolates were Enterococcus faecium (27 isolates, 62%), Enterococcus faecalis (9 isolates, 21%), Enterococcus solitarius (4 isolates, 9%), Enterococcus durans (2 isolates, 4%), 1 isolate Enterococcus sulfurous (2%), and Enterococcus raffinosus (2%). In total, 26 isolates were detected in the study in the presence of vanA genes (24 isolates E. faecium, 2 isolates E. faecalis) and 18 isolates detected in the presence of vanB genes (7 isolates E. faecalis, 4 isolates E. solitarius, 3 isolates E. faecium, 2 isolates E. durans, 1 isolate E. sulfurous, and E. raffinosus). The results of this study showed the local dominance character of the vanA gene of hospital VRE isolates that were carriers of genes associated with high resistance to vancomycin, teicoplanin, and occasionally linezolid.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• Clostridioides difficile * genetika   MeSH
• Enterococcus faecium * genetika   MeSH
• enterokoky rezistentní vůči vankomycinu * genetika   MeSH
• grampozitivní bakteriální infekce * mikrobiologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• teikoplanin farmakologie   MeSH
• vankomycin farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

Enterococcus faecalis is an important factor in nosocomial infections. The aim of this study was the isolation of the pathogenic genes of Enterococcus faecalis in mouth infection and the study of the expression of these genes by real-time PCR. In this study, 60 isolates of E. faecalis were isolated from oral infections. The presence and frequency of cyl, hyl, and esp genes and their expression by ionic liquid were evaluated using real-time PCR. MIC was determined by broth dilution method and biofilm production was measured, then biofilm inhibition ability and cytotoxicity test were performed by MTT method. The esp, cyl, and hyl genes were observed in 10, 11, and 2 isolates, respectively. cyl gene with the highest frequency of expression in the treated group was reduced by 1.14% under the influence of ionic liquid with methionine base. The results of MIC and Sub MIC concentrations were obtained with the effect of ionic liquid including 125 and 225 μg/mL, respectively. Amino-acid-based ionic liquids can also reduce biofilm production at sub-MIC concentrations (P < 0.05), and changes in cytotoxicity at different concentrations and over time are significant (P-value < 0.001). E. faecalis strains are genetically diverse and this indicates the polyclonal prevalence of strains in clinical specimens. Combination treatment of ionic liquid with common antimicrobial drugs has good antibacterial effects against Enterococcus species, and ionic liquid with a minimum dose can be a good alternative to single-drug treatment of Enterococcus infections.

• MeSH
• aminokyseliny MeSH
• antibakteriální látky farmakologie   MeSH
• biofilmy MeSH
• Enterococcus faecalis MeSH
• grampozitivní bakteriální infekce * farmakoterapie   mikrobiologie   MeSH
• iontové kapaliny * farmakologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• methionin genetika   farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Mast cells are potent immune sensors of the tissue microenvironment. Within seconds of activation, they release various preformed biologically active products and initiate the process of de novo synthesis of cytokines, chemokines, and other inflammatory mediators. This process is regulated at multiple levels. Besides the extensively studied IgE and IgG receptors, toll-like receptors, MRGPR, and other protein receptor signaling pathways, there is a critical activation pathway based on cholesterol-dependent, pore-forming cytolytic exotoxins produced by Gram-positive bacterial pathogens. This pathway is initiated by binding the exotoxins to the cholesterol-rich membrane, followed by their dimerization, multimerization, pre-pore formation, and pore formation. At low sublytic concentrations, the exotoxins induce mast cell activation, including degranulation, intracellular calcium concentration changes, and transcriptional activation, resulting in production of cytokines and other inflammatory mediators. Higher toxin concentrations lead to cell death. Similar activation events are observed when mast cells are exposed to sublytic concentrations of saponins or some other compounds interfering with the membrane integrity. We review the molecular mechanisms of mast cell activation by pore-forming bacterial exotoxins, and other compounds inducing cholesterol-dependent plasma membrane perturbations. We discuss the importance of these signaling pathways in innate and acquired immunity.

• MeSH
• buněčná membrána imunologie   metabolismus   mikrobiologie   patologie   MeSH
• buněčná smrt MeSH
• buněčné mikroprostředí MeSH
• cholesterol metabolismus   MeSH
• cytokiny metabolismus   MeSH
• cytotoxiny metabolismus   MeSH
• degranulace buněk MeSH
• grampozitivní bakteriální infekce imunologie   metabolismus   mikrobiologie   patologie   MeSH
• grampozitivní bakterie imunologie   metabolismus   MeSH
• interakce hostitele a patogenu MeSH
• lidé MeSH
• mastocyty imunologie   metabolismus   mikrobiologie   patologie   MeSH
• mediátory zánětu metabolismus   MeSH
• vápníková signalizace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Excessive use of antibiotics contributes to the selection of resistant bacteria and intestinal colonization with multiresistant pathogens poses a risk factor for subsequent infections. The present study assessed vancomycin-resistant enterococci (VRE) carriage rates in patients admitted to our tertiary care hospital. Stool samples sent for routine culturing were screened with vancomycin containing solid or broth enrichment media. VRE isolates were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and antibiotic susceptibilities were tested by E-test. Vancomycin resistance genes were detected by polymerase chain reaction. Medical records of carriers were examined for suspected risk factors for colonization. Altogether 3025 stool specimens were analyzed. Solid media identified a VRE carriage rate of 2.2% while broth enrichment detected 5.8%. Seventy percent of the isolates were Enterococcus faecium. VanB genotype was detected in 38.2%, VanA in 37.3%, VanC1 in 22.6%, and VanC2 in 1.9%. All VRE were sensitive to linezolid, daptomycin, and tigecycline. Collective risk factors for carriage were diabetes, normal flora absence, Clostridioides difficile positivity, longer hospital stay, and advanced age. 78.5% of the carriers received antibiotic therapy which was metronidazole in most cases (47.3%). We recommend regular screening of risk groups such as patients with diabetes, history of recent hospitalization, or former C. difficile infection as an imperative step for preventing VRE dissemination.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• centra terciární péče MeSH
• dítě MeSH
• dospělí MeSH
• enterokoky rezistentní vůči vankomycinu izolace a purifikace   MeSH
• feces mikrobiologie   MeSH
• genotyp MeSH
• grampozitivní bakteriální infekce farmakoterapie   epidemiologie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• přenašečství epidemiologie   mikrobiologie   MeSH
• retrospektivní studie MeSH
• rezistence na vankomycin genetika   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• střeva mikrobiologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Maďarsko MeSH

OBJECTIVES: The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance programme monitoring the in vitro activity of a panel of antimicrobial agents against clinically important bacterial isolates. Data for Gram-positive and Gram-negative isolates collected in Eastern Europe between 2011 and 2016 are presented here. METHODS: Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method using CLSI guidelines. Antimicrobial susceptibility was assessed using EUCAST breakpoints. RESULTS: Nine Eastern European countries submitted 4289 isolates. Among Acinetobacter baumannii, resistance to levofloxacin, amikacin and meropenem was 77.5%, 63.4% and 62.2%, respectively. Multidrug resistance among A. baumannii was higher in 2015 than in previous years (44.1% in 2011 and 71.0% in 2015), decreasing to 51.7% in 2016. The multidrug resistance percentage for Pseudomonas aeruginosa was 26.9% and was relatively stable over time. The percentage of extended-spectrum β-lactamase (ESBL)-positive isolates among Escherichia coli and Klebsiella pneumoniae was 20.1% and 55.7%, respectively. Resistance to amikacin, meropenem and tigecycline was low among E. coli and K. pneumoniae and the ESBL-producing subset (≤5.9%). Among Staphylococcus aureus isolates, 36.7% were methicillin-resistant (MRSA); percentages varied year-on-year. No S. aureus isolates, including MRSA, were resistant to linezolid, vancomycin or tigecycline. Among Enterococcus faecium isolates, resistance was 22.6% to vancomycin and 2.3% to linezolid; no isolates were resistant to tigecycline. CONCLUSION: This study shows low resistance to meropenem and tigecycline among Enterobacteriaceae isolates and continued activity of linezolid, vancomycin and tigecycline against Gram-positive organisms. However, antimicrobial resistance continues to be problematic in Eastern Europe and requires continued surveillance.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence MeSH
• dospělí MeSH
• gramnegativní bakteriální infekce mikrobiologie   MeSH
• gramnegativní bakterie klasifikace   účinky léků   genetika   izolace a purifikace   MeSH
• grampozitivní bakteriální infekce mikrobiologie   MeSH
• grampozitivní bakterie klasifikace   účinky léků   genetika   izolace a purifikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• tigecyklin farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• východní Evropa MeSH

Vancomycin-resistant enterococci (VRE) are nosocomial pathogens of increasing medical importance. This study involved 121 VRE selectively obtained from a representative set of 1464 samples collected from various sources in the north-eastern part of the Czech Republic. In total, 119 VRE belonged to Enterococcus faecium and two to Enterococcus faecalis. All isolates of E. faecium were resistant to at least three antibiotic classes. The resistance genes vanA, erm(B), tet(M), tet(L), aac(3)-IIIa and aac(6')-aph(2'') were detected. We assigned the E. faecium to sequence types ST5, ST18, ST38, ST64, ST92, ST273, ST549 and ST640. In E. faecium isolates, we identified the presence of replicases rep20pLG1 , rep2pRE25 , rep17pRUM , rep21pVEF1/2 and rep14pRI1 , as well as relaxases relpEF1 , relpLG1 , relpCIZ2 , relpRE25 and relpRUM . The presence of the toxin-antitoxin system axe-txe was detected mainly among isolates of hospital origin. The A and D types of transposon Tn1546 were those occurring most frequently. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first extensive study of vancomycin-resistant enterococci of diverse origin in a single well-defined area of the Czech Republic. The isolates were investigated for their antibiotic resistance, epidemiological characteristics and plasmid characteristics. Based on the results obtained, we can make assumptions as to the ways that vancomycin resistance is disseminated throughout the environment including humans and animals.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• Enterococcus faecalis účinky léků   genetika   izolace a purifikace   MeSH
• Enterococcus faecium účinky léků   genetika   izolace a purifikace   MeSH
• enterokoky rezistentní vůči vankomycinu klasifikace   genetika   izolace a purifikace   MeSH
• grampozitivní bakteriální infekce epidemiologie   mikrobiologie   MeSH
• lidé MeSH
• plazmidy genetika   MeSH
• rezistence na vankomycin genetika   MeSH
• systémy toxin-antitoxin genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

PURPOSE: Recent research shows an increasing recognition that organisms not traditionally considered infectious in nature contribute to disease processes. Propionibacterium acnes (P. acnes) is a gram-positive, aerotolerant anaerobe prevalent in the sebaceous gland-rich areas of the human skin. A ubiquitous slow-growing organism with the capacity to form biofilm, P. acnes, recognized for its role in acne vulgaris and medical device-related infections, is now also linked to a number of other human diseases. While bacterial culture and molecular techniques are used to investigate the involvement of P. acnes in such diseases, definitive demonstration of P. acnes infection requires a technique (or techniques) sensitive to the presence of biofilms and insensitive to the presence of potential contamination. Fortunately, there are imaging techniques meeting these criteria, in particular, fluorescence in situ hybridization and immunofluorescence coupled with confocal laser scanning microscopy, as well as immunohistochemistry. METHODS: Our literature review considers a range of microscopy-based studies that provides definitive evidence of P. acnes colonization within tissue from a number of human diseases (acne vulgaris, degenerative disc and prostate disease and atherosclerosis), some of which are currently not considered to have an infectious etiology. RESULTS/CONCLUSION: We conclude that P. acnes is an opportunistic pathogen with a likely underestimated role in the development of various human diseases associated with significant morbidity and, in some cases, mortality. As such, these findings offer the potential for new studies aimed at understanding the pathological mechanisms driving the observed disease associations, as well as novel diagnostic strategies and treatment strategies, particularly for degenerative disc disease. These slides can be retrieved under Electronic Supplementary Material.

• MeSH
• acne vulgaris diagnostické zobrazování   mikrobiologie   MeSH
• biofilmy * MeSH
• degenerace meziobratlové ploténky * diagnostické zobrazování   mikrobiologie   MeSH
• grampozitivní bakteriální infekce * diagnostické zobrazování   mikrobiologie   MeSH
• lidé MeSH
• mikroskopie * MeSH
• Propionibacterium acnes * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Most patients with chronic lower back pain (CLBP) exhibit degenerative disc disease. Disc specimens obtained during initial therapeutic discectomies are often infected/colonized with Propionibacterium acnes, a Gram-positive commensal of the human skin. Although pain associated with infection is typically ascribed to the body's inflammatory response, the Gram-positive bacterium Staphylococcus aureus was recently observed to directly activate nociceptors by secreting pore-forming α-hemolysins that disrupt neuronal cell membranes. The hemolytic activity of P. acnes in cultured disc specimens obtained during routine therapeutic discectomies was assessed through incubation on sheep-blood agar. The β-hemolysis pattern displayed by P. acnes on sheep-blood agar was variable and phylogroup-dependent. Their molecular phylogroups were correlated with their hemolytic patterns. Our findings raise the possibility that pore-forming proteins contribute to the pathogenesis and/or symptomology of chronic P. acnes disc infections and CLBP, at least in a subset of cases.

• MeSH
• chronická nemoc MeSH
• grampozitivní bakteriální infekce komplikace   mikrobiologie   patologie   MeSH
• hemolýza * MeSH
• lidé MeSH
• lumbalgie komplikace   mikrobiologie   patologie   MeSH
• meziobratlová ploténka mikrobiologie   patologie   MeSH
• ovce MeSH
• Propionibacterium acnes fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH