A novel Enterococcus faecalis bacteriophage Ef212: biological and genomic features.

This study aimed to isolate and characterize biological and genomic features of a phage infecting Enterococcus faecalis. The phage was isolated from environmental water and temperature and pH stability, one-step growth curve, and multiplicity of infection (MOI) were determined. Whole genome sequencing (WGS) and structural and functional annotations were performed. Its antibiofilm activity was also evaluated. The optimal MOI was 0.01, the latency period was 5 min, and the burst size was 202 plaque forming unit (PFU). High phage survival rates were observed at between pH 4-10 and temperatures between 4-50 °C. WGS and Transmission electron microscopy (TEM) showed that it was an Efquatrovirus representing siphovirus morphotype respectively. It was named as Enterococcus phage Ef212 and has a linear 40,690 bp double-stranded DNA with 45.3% G + C content (GenBank accession number: OR052631). BACPHLIP tool demonstrated that Enterococcus phage Ef212 is a lytic phage (88%). A total of 80 open reading frames (ORFs) were found and there were no antibiotic resistance genes, pathogenicity, virulence genes, or tRNAs in the phage genome. It was diverged from the most similar phages (identity, 88.35%; coverage, 89%) by phylogenetic analysis. Phage Ef212 shared a large part of its genome (60/80) with several other phages, yet some unique parts were found in their genomes. Host range analysis showed that phage Ef212 showed lytic activity against vancomycin-resistant and vancomycin-susceptible E. faecalis clinical isolates. This novel phage Ef212 showed the ability to inhibit and reduce the biofilm formation by around 42% and 38%, respectively. The biological and genomic features indicate that having an effective antibacterial activity, phage Ef212 seemed a promising therapeutic and biocontrol agent.

In vitro activity of cefiderocol against carbapenem-resistant Acinetobacter baumannii carrying various ß-lactamase encoding genes.

OBJECTIVES: This study aimed to determine the in vitro efficacy of cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates and evaluate the disk-diffusion (DD) method as an alternative method to broth-microdilution (BMD). METHODS: Totally 89 CRAB isolates were included. Cluster analysis was determined by Pulsed-Field Gel Electrophoresis (PFGE). Resistance genes; blaOXA-51, blaOXA-23, blaOXA-24, blaOXA-58,blaPER-1, blaNDM, blaIMP and mcr-1 were screened. Cefiderocol susceptibility testing was performed by both DD and BMD. Interpretation was made according to EUCAST and CLSI. Categorical agreement (CA), minor errors (mEs), major errors (MEs), and very major errors (VMEs) were determined. RESULTS: PFGE revealed 5 distinct pulsotypes; 86 of the isolates were extensively drug-resistant (XDR). All the isolates were negative for blaNDM, blaIMP, mcr-1, while positive for blaOXA-58 and blaOXA51. blaPER-1 was positive for 33.7%; blaOXA-23 for 74.2%; blaOXA-24 for 12.3%. According to CLSI, the MEs rate was 1.85%, mEs was 7.86% and there were no VMEs. According to EUCAST, MEs rate was 3.70%, there were no mEs and VMEs. CA was 91% for CLSI and 97.8% for EUCAST. MICs of cefiderocol against A. baumannii isolates ranged from 0.06 to > 128 mg/L, with MIC50 and MIC90 values of 0.5 and > 128 mg/L, respectively. CONCLUSIONS: Cefiderocol susceptibility was 60.7% in CRAB isolates. MIC50, MIC90 of blaPER-1 positive and blaPER-1 negative groups were > 128/>128 and 0.25/>128 mg/L. A correlation between the presence of blaPER-1 and cefiderocol resistance was observed (p < 0.0001). Among colistin-resistant isolates, the presence of blaPER-1 was 47.1% and 75% of them were resistant to cefiderocol respectively.

Biological and genomic characteristics of three novel bacteriophages and a phage-plasmid of Klebsiella pneumoniae.

Bacteriophages have emerged as promising candidates for the treatment of difficult-to-treat bacterial infections. The aim of this study is to isolate and characterize phages infecting carbapenem-resistant and extended-spectrum beta-lactamase producer Klebsiella pneumoniae isolates. Water samples were taken for the isolation of bacteriophages. One-step growth curve, the optimal multiplicity of infection (MOI), thermal and pH stabilities, transmission electron microscopy and whole-genome sequencing of phages were studied. Four phages were isolated and named Klebsiella phage Kpn02, Kpn17, Kpn74, and Kpn13. The optimal MOI and latent periods of phage Kpn02, Kpn17, Kpn74, and Kpn13 were 10, 1, 0.001, and 100 PFU/CFU and 20, 10, 20, and 30 min, respectively. Burst sizes ranged from 811 to 2363. No known antibiotic resistance and virulence genes were identified. No tRNAs were detected except Klebsiella phage Kpn02 which encodes 24 tRNAs. Interestingly, Klebsiella phage Kpn74 was predicted to be a lysogenic phage whose prophage is a linear plasmid molecule with covalently closed ends. Of the Klebsiella-infecting phages presented in current study, virulent phages suggest that they may represent candidate therapeutic agents against MDR K. pneumoniae, based on short latent period, high burst sizes and no known antibiotic resistance and virulence genes in their genomes.

Evaluation of the Lytic Activity of Various Phage Cocktails Against, ESBL-Producer, Non-Producer and Carbapenem-Resistant Escherichia coli Isolates.

Bacteriophages have been proposed as an alternative therapy for the treatment of bacterial infections. This research aims to determine the lytic activity of bacteriophage-cocktails (BC) against carbapenem-resistant (CR-EC), ESBL-producer (EP-EC), and non-producer (NP-EC) E. coli isolates. Related resistance genes in 87 E. coli isolates were screened by PCR. The efficacies of BCs were determined by spot test and lytic zones were evaluated from fully-confluent to opaque. MOIs of the BCs were compared for fully-confluent and opaque lytic zones. BCs were also evaluated in terms of their biophysical characteristics including latency, burst size, pH and temperature stabilities. Among EP-EC, 96.9% of the isolates carry blaCTX-M, 25% of them blaSHV and 15.6% of them carry blaTEM. All CR-EC isolates carried blaOXA-48, but not blaKPC and blaNDM. CR-EC isolates were the least susceptible for the each of four BCs. MOIs for ENKO, SES and INTESTI-phage forming fully-confluent zone in E. coli isolates EC3 (NP-EC), EC8 (EP-EC) and EC27 (NP-EC), respectively were 10, 100 and 1, respectively. MOIs for ENKO, SES and INTESTI opaque zone in EC19 (EP-EC), EC10 (EP-EC), EC1(NP-EC), respectively were 0.01, 0.01, 0.1 PFU/CFU, respectively. The MOI for PYO-phage forming a semi-confluent zone in EC6 (NP-EC) isolate was 1 PFU/CFU. The phages were thermally stable and tolerant to a wide pH range. Comparison of MOIs according to lysis zone characteristics demonstrated that the activities of phages in phage cocktails vary depending on the characteristics of each bacterial host. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01074-9.

The impacts of 13 novel mutations of SARS-CoV-2 on protein dynamics: In silico analysis from Turkey.

SARS-CoV-2 inherits a high rate of mutations making it better suited to the host since its fundamental role in evolution is to provide diversity into the genome. This research aims to identify variations in Turkish isolates and predict their impacts on proteins. To identify novel variations and predict their impacts on protein dynamics, in silico methodology was used. The 411 sequences from Turkey were analysed. Secondary structure prediction by Garnier-Osguthorpe-Robson (GOR) was used. To find the effects of identified Spike mutations on protein dynamics, the SARS-CoV-2 structures (PDB:6VYB, 6M0J) were uploaded and predicted by Cutoff Scanning Matrix (mCSM), DynaMut and MutaBind2. To understand the effects of these mutations on Spike protein molecular dynamics (MD) simulation was employed. Turkish sequences were aligned with sequences worldwide by MUSCLE, and phylogenetic analysis was performed via MegaX. The 13 novel mutations were identified, and six of them belong to spike glycoprotein. Ten of these variations revealed alteration in the secondary structure of the protein. Differences of free energy between the reference sequence and six mutants were found below zero for each of six isolates, demonstrating these variations have stabilizing effects on protein structure. Differences in vibrational entropy calculation revealed that three variants have rigidification, while the other three have a flexibility effect. MD simulation revealed that point mutations in spike glycoprotein and RBD:ACE-2 complex cause changes in protein dynamics compared to the wild-type, suggesting possible alterations in binding affinity. The phylogenetic analysis showed Turkish sequences distributed throughout the tree, revealing multiple entrances to Turkey.

Comparison of in vitro activities of plazomicin and other aminoglycosides against clinical isolates of Klebsiella pneumoniae and Escherichia coli.

OBJECTIVES: To compare the in vitro activity of plazomicin and two older aminoglycosides (gentamicin and amikacin) against 180 isolates of Escherichia coli and Klebsiella pneumoniae, including subsets of 60 non-ESBL-producing, 60 ESBL-producing and 60 carbapenem-resistant (46 carrying blaOXA-48, 11 carrying blaNDM and 3 carrying blaOXA-48 and blaNDM) strains. METHODS: MICs of plazomicin, gentamicin and amikacin were determined by a gradient diffusion method. Gentamicin and amikacin MICs were interpreted according to CLSI criteria and EUCAST breakpoint tables. Plazomicin MICs were interpreted using FDA-defined breakpoints. RESULTS: All non-ESBL-producing and ESBL-producing isolates were susceptible to plazomicin. The plazomicin susceptibility rate (71.7%) in carbapenem-resistant isolates was significantly higher than those observed for gentamicin (45%) and amikacin (56.7% and 51.7% according to CLSI and EUCAST breakpoints, respectively). Gentamicin, amikacin and plazomicin susceptibility rates (35.6% for gentamicin; 44.4% and 37.8% for amikacin according to CLSI and EUCAST breakpoints, respectively; 64.4% for plazomicin) in carbapenem-resistant K. pneumoniae were significantly lower than those observed for carbapenem-resistant E. coli isolates (73.3% for gentamicin; 93.3% for amikacin and plazomicin). Gentamicin, amikacin and plazomicin susceptibility rates for blaNDM-positive isolates were lower than those observed for blaOXA-48-positive isolates, but differences were not statistically significant. Among the isolates that were non-susceptible to both gentamicin and amikacin, the plazomicin susceptibility rate was less than 30%. CONCLUSIONS: Although plazomicin showed excellent in vitro activity against carbapenem-susceptible isolates, the plazomicin resistance rate increased to 35.6% among carbapenem-resistant K. pneumoniae and further increased to 45.5% among blaNDM-positive isolates.

Antibacterial Resistance in Lower Respiratory Tract Bacterial Pathogens: A Multicenter Analysis from Turkey.

INTRODUCTION: This study aimed to evaluate the etiology of lower respiratory tract infections (LRTIs) and their antibiotic resistance. METHODOLOGY: Bacterial culture results of LRT samples from 17 hospitals between 2016-2019 were included in the study. All isolates were identified and AST were performed by automated microbiology systems. AST was performed according to EUCAST. RESULTS: Non-duplicate 30,051 (26,890 HA and 3156 CA) isolates detected as causative pathogen. LRTIs are caused by 85.1% Gram-negative bacterial pathogens and 14.9% Gram-positive. The most common isolates among HA pathogens were Acinetobacter spp. (27.4%), P.aeruginosa (22.2%), K.pneumoniae (17.9%); among CA pathogen S.pneumoniae (19.9%), P. aeruginosa (18.9%), H.influenzae (14.6%). ESBL rate was 62.5% in K.penumoniae; 53.1% in E.coli; 19.1% in Klebsiella spp; 13.9% in Enterobacter spp.; 8.6% in Proteus spp.; 6.3% in Citrobacter spp.; and 4.3% in Serratia spp. Resistance rates to carbapenems and colistin were 92.8% and 12.8% in A baumannii, 39.8% and 7.5% in P.aeruginosa, 47.3% and 18.5% in K.penumoniae. Among staphylococci, 27.3% of S. aureus and 82.4% of CoNS were methicillin resistant. 7.6% of E.faecium and 0.9% of E.faecalis were vancomycin resistant.  Linezolid resistant S. aureus, CoNS, E.faecalis and E.faecium rates were 0.3%, 2.9%, 0.0% and 4.6%. Inducible clindamycin resistant rate was 17.2% in S. aureus 38.2% in CoNS. Non-susceptible S.pneumoniae isolate rate to penicillin was 37.0%. 6.5% of S.maltophilia and 4.4% of B.cepacia isolates were resistant to trimethoprim/sulfamethoxazole. CONCLUSIONS: Antibiotic resistance was mainly observed among A.baumannii and K.pneumoniae and continuous surveillance of antimicrobial resistance patterns in the management of LRTIs is important.

An Investigation into Bacterial Bloodstream Infections and Antibiotic Resistance Profiles in a Tertiary Hospital for a Ten-Year Period.

BACKGROUND: Bloodstream infections are one of the major causes of healthcare-associated morbidity and mortality. The present study aims to investigate the prevalence of the microorganisms isolated from blood cultures and to evaluate susceptibilities to antimicrobial agents in a tertiary center, Gulhane Training and Research Hospital, Ankara, Turkey. METHODS: Blood cultures (BCs) were incubated in BACTEC/9050 (Becton Dickinson, USA) (2007 - 2015) and BacT/ALERT (bio-Merieux, France) (2014 - 2016) automated systems. PhoenixTM 100 system (Becton Dickinson, USA) (2007 - 2014), MALDI-TOF MS (Bruker, USA) (2015 - 2016) and conventional techniques were used for the identification of isolated microorganisms. According to CLSI (2007 - 2014) and EUCAST (2015 - 2016) criteria, Kirby-Bauer disc diffusion method, PhoenixTM system, and broth microdilution were applied for antimicrobial susceptibility testing. Two five-year periods were statistically compared regarding antibiotic resistance. RESULTS: From the overall evaluated 31,380 BCs, 7,367 cultures (23.5%) were positive, excluding 503 BCs (6.4%), which were interpreted as contamination. Of 7,367 isolated microorganisms, 3,680 (50.0%) were gram-negative, 3,303 (44.8%) were gram-positive bacteria, and 384 (5.2%) were fungi. Coagulase-negative staphylococci (CoNS) were predominantly isolated (n = 2,075; 28.2%) among gram-positives. E.coli (n = 978; 13.3%) was the most frequently isolated gram-negative species. Between the first and the last five-year period, three genera (Enterococcus spp., Acinetobacter spp., Streptococcus spp.) showed significant differences when isolated, and only Enterococcus spp. showed increased isolation rates. In total, 90.3% of CoNS and 32% of S. aureus were methicillin-resistant. Only 75 strains of Enterococcus spp. (12.1%) were vancomycin-resistant. ESBL was detected in 40.6% of E. coli and 30.7% of Klebsiella spp. isolates. Carbapenem resistance showed a significant increase, particularly in K. pneumoniae (> 20%). CONCLUSIONS: The findings suggest that there was a threatening condition in antimicrobial resistance rates, especially for some antimicrobials between two periods. Although antimicrobial resistance is usually associated with MRSA, carbapenem resistance, ESBL, and VRE, the problem is far beyond these definitions, consisting of not just medicine, but also commercial companies, food industry, veterinarians, and other areas.

Prevalence and Quantity of Parvovirus B19 DNA Among Blood Donors from a Regional Blood Center in Turkey.

OBJECTIVE: Parvovirus B19 causes a range of diseases and morbidity in humans and is transmissible by transfusion of blood, blood components and plasma derivatives. The objective of the study was to investigate the prevalence and quantity of B19 DNA among blood donors. METHOD: Totally 1053 samples were collected from March to July 2016 at a blood bank for detection of Parvovirus B19 DNA and serological status of blood donors. Testing of the presence of viral DNA was performed by a quantitative real-time PCR with a 101 copies/ml detection limit. All DNA positive and randomly selected 267 samples were tested for the presence of anti-B19 IgM and IgG by ELISA. RESULTS: Age distribution of donors was between 18-64; mean age was 27 and median was 23. Among the 1053 samples, 5 (0.47%) had PB19 DNA. All PB19 DNA positive donations had both B19 IgM and IgG antibodies. The DNA level for positive donations were between 0.9 × 102 to 3.1 × 104 copies/ml. IgG and IgM were present in 59.9% (160/267) and 0,74% (2/267) respectively among the healthy donors without PB19 DNA. CONCLUSION: Detected DNA concentration was less than 105 copies/ml. The presence of IgM in low level PB19 DNA positive donors may indicate that there might be a risk in transmission of PB19 to particularly immunosuppressed recipients. The clinical follow-up of blood donation with low level of PB19DNA should be considered to answer the questions about blood safety.

Electrospinning of linezolid loaded PLGA nanofibers: effect of solvents on its spinnability, drug delivery, mechanical properties, and antibacterial activities.

Objective: The choice of a desirable solvent/solvent system is fundamental for optimization of electrospinning by altering the rheological and electrostatic properties of the polymer solutions.Methods: The effects of the solvents and their properties on the viscosity and spinnability of the polymer solutions and the diameter, morphology, in vitro drug release, drug release mechanisms, antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and mechanical properties of electrospun poly-(d,l-lactide-co-glycolide) (PLGA) nanofibers were investigated. Dichloromethane (DCM), dimethylformamide (DMF), various ratios of DCM:DMF, and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) were used as solvents.Results: Although solutions containing DCM/DMF alone were not spinnable, different ratios of DCM:DMF and HFIP were determined as suitable solvents to produce nanofibers because of high enough conductivity, viscosity, and low enough surface tension of the solutions. The DCM:DMF ratio was highly effective on viscosity, nanofiber diameter, morphology, and linezolid release rate. The viscosity of HFIP containing solution was higher and the obtained nanofibers were thicker and smoother with better mechanical properties. The release of nanofibers containing HFIP at a concentration of 10% w/v PLGA was more prolonged than nanofibers containing DCM:DMF mixture. The effect of linezolid content on nanofibers was also investigated. As the amount of linezolid increased, nanofiber diameter and drug release increased and bead formation was observed. While antibacterial activity with nanofibers for which DCM:DMF was used, lasted for 13 days, it was extended to 16 days in nanofibers for which HFIP was used.Conclusions: Type and ratio of the solvent system affected viscosity and spinnability of the solutions, the average nanofiber diameter, morphology, in vitro activity and mechanical properties of the obtained electrospun nanofibers.

In vitro and in vivo evaluation of linezolid loaded electrospun PLGA and PLGA/PCL fiber mats for prophylaxis and treatment of MRSA induced prosthetic infections.

In this study, it was aimed to formulate linezolid loaded electrospun PLGA and PCL fiber mats doing controlled drug release, to be used in the treatment and prophylaxis of the prosthesis related infections. The effect of PLGA concentration, PLGA to PCL ratio and the amount of linezolid on the fiber and mat properties were examined. Fiber diameter has been shown to increase with increasing amount of PLGA and linezolid. Increase in PLGA amount resulted in reduced linezolid release, whereas increase in linezolid amount resulted in increased drug release. All PLGA fiber mats have shown to have favorable encapsulation efficiency (≥73%) and mechanical properties. Encapsulation efficiency and the mechanical properties deteriorated with the addition of PCL to the formulations. PLGA fiber mats have shown a biphasic controlled release and in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), pattern up to one month. The formulation selected as the optimum has been evaluated in vivo on the infected rats, which had prosthetic implantation after bone fracture. Consequently, it has been demonstrated microbiologically and histopathologically that a more efficient therapy and prophylaxis have been achieved with a 37-fold lower dose of linezolid.

Medicinal leech therapy-an overall perspective.

Complementary medicine methods have a long history, but modern medicine has just recently focused on their possible modes of action. Medicinal leech therapy (MLT) or hirudotherapy, an old technique, has been studied by many researchers for possible effects on various diseases such as inflammatory diseases, osteoarthritis, and after different surgeries. Hirudo medicinalis has widest therapeutic usage among the leeches, but worldwide, many different species were tested and studied. Leeches secrete more than 20 identified bioactive substances such as antistasin, eglins, guamerin, hirudin, saratin, bdellins, complement, and carboxypeptidase inhibitors. They have analgesic, anti-inflammatory, platelet inhibitory, anticoagulant, and thrombin regulatory functions, as well as extracellular matrix degradative and antimicrobial effects, but with further studies, the spectrum of effects may widen. The technique is cheap, effective, easy to apply, and its modes of action have been elucidated for certain diseases. In conclusion, for treatment of some diseases, MLT is not an alternative, but is a complementary and/or integrative choice. MLT is a part of multidisciplinary treatments, and secretes various bioactive substances. These substances vary among species and different species should be evaluated for both treatment capability and their particular secreted molecules. There is huge potential for novel substances and these could be future therapeutics.

[Investigation of various virulence factors among the hospital and community-acquired Staphylococcus aureus isolates by real-time PCR method]. / Hastane ve Toplum Kaynakli Staphylococcus aureus Izolatlarinda Çesitli Virülans Faktörlerinin Gerçek Zamanli PCR Yöntemiyle Arastirilmasi

Staphylococcus aureus is the most common cause of skin and soft tissue infections in the community and the most important cause of nosocomial infections. In this research, it was aimed to detect the presence of staphylococcal enterotoxin A to D (SEA, SEB, SEC and SED, respectively), toxic shock syndrome toxin-1 (TSST-1), Panton-Valentine leukocidin (PVL) and SCCmec phenotype in methicillin-resistant S.aureus (MRSA) isolates and to demonstrate the genotypic association between hospital acquired and community acquired isolates. In the study the virulence factors of 147 S.aureus strains isolated from various clinical samples at Gulhane Military Medical Academy Hospital Microbiology Laboratory between 2007 and 2010 were investigated by real-time polymerase chain reaction. MLVA (multiple locus variable number of tandem repeat analysis) method was used to demonstrate the genotypic association between hospital-and community-acquired isolates. Seventy-two (%48.9) of 147 S.aureus isolates were determined as community acquired and 75 (%51.1) as hospital acquired. Ninety-three (63.2%) isolates possesed at least one toxin (77 strains harboured one, and 16 strains harboured more than one). Of the isolates in which toxin was detected 59.1% (55/93) were hospital acquired, 40.9% (38/93) were community acquired. SEA was determined in 59 (40.1%), SEB in 8 (5.4%), SEC in 12 (8.1%), SED in 8 (5.4%), TSST- 1 in 17 (11.5%) and PVL in 6 (4.0%) of the isolates. Methicillin resistance was determined in 61.1% (44/72) of the hospital acquired isolates and 6.7% of the (5/75) community acquired isolates. In our study, SCCmec type III was detected in 90.9% (40/44) of hospital acquired MRSA isolates and SCCmec type IV in 40.0% (2/5) of community acquired MRSA isolates. Most of the strains (40/47; 85.1%) carrying SEA were hospital acquired, and they were determined as methicillin-resistant. According to MLVA, hospital and community acquired groups' clustering rates, number of clones, number of unique profile were determined as; 73.6% and 57.3%; 34% and 47%; 19% and 32%, respectively. It was concluded that high prevalence of SEA toxin in hospital acquired MRSA isolates indicated that there was a possible association between the presence of toxin and antimicrobial resistance.

In vitro antimicrobial activity of propolis samples from different geographical origins against certain oral pathogens.

Propolis is an agent having antimicrobial properties, however, its composition can vary depending on the area where it is collected. In the present study, the antimicrobial activity of five propolis samples, collected from four different regions in Turkey and from Brazil, against nine anaerobic strains was evaluated. Ethanol extracts of propolis (EEP) were prepared from propolis samples and we determined minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of EEP on the growth of test microorganisms by using agar dilution method. All strains were susceptible and MIC values ranged from 4 to 512 microg/ml for propolis activity. Propolis from Kazan-Ankara showed most effective MIC values to the studied microorganisms. MBC values of Kazan-Ankara EEP samples were ranged from 8 to 512 microg/ml. Death was observed within 4 h of incubation for Peptostreptococcus anaerobius and micros and Lactobacillus acidophilus and Actinomyces naeslundii, while 8 h for Prevotella oralis and Prevotella melaninogenica and Porphyromonas gingivalis, 12 h for Fusobacterium nucleatum, 16 h for Veillonella parvula. It was shown that propolis samples were more effective against Gram positive anaerobic bacteria than Gram negative ones. The organic chemical compositions of EEPs were determined by high-resolution gas chromatography coupled to mass spectrometry (GC-MS). The main compounds of EEPs were flavonoids such as pinobanksin, quercetin, naringenin, galangine, chrysin and aromatic acids such as cafeic acid. Because of increased antimicrobial resistance, propolis may be kept in mind in the treatment of oral cavity diseases.