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Majid Taati Moghadam,1 Nour Amirmozafari,1 Aref Shariati,1,2 Masoumeh Hallajzadeh,1 Shiva Mirkalantari,1 Amin Khoshbayan,1,2 Faramarz Masjedian Jazi1,3 1Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; 2Student Research Committee, Iran University of Medical Sciences, Tehran, Iran; 3Microbial Biotechnology Research Center, Iran University of Medical Science, Tehran, IranCorrespondence: Faramarz Masjedian JaziDepartment of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranTel +989123905926Email Masjedian.f@iums.ac.irAbstract: Nowadays the most important problem in the treatment of bacterial infections is the appearance of MDR (multidrug-resistant), XDR (extensively drug-resistant) and PDR (pan drug-resistant) bacteria and the scarce prospects of producing new antibiotics. There is renewed interest in revisiting the use of bacteriophage to treat bacterial infections. The practice of phage therapy, the application of phages to treat bacterial infections, has been around for approximately a century. Phage therapy relies on using lytic bacteriophages and purified phage lytic proteins for treatment and lysis of bacteria at the site of infection. Current research indicates that phage therapy has the potential to be used as an alternative to antibiotic treatments. It is noteworthy that, whether phages are used on their own or combined with antibiotics, phages are still a promising agent to replace antibiotics. So, this review focuses on an understanding of challenges of MDR, XDR, and PDR bacteria and phages mechanism for treating bacterial infections and the most recent studies on potential phages, cocktails of phages, and enzymes of lytic phages in fighting these resistant bacteria.Keywords: bacteriophage, drug resistant, MDR, XDR, PDR

Many combined therapies have been proposed to enhance radiotherapy outcome, but they have several limitations. As a new feasible strategy, combination of radiotherapy with bacteria showed a significant positive impact on the tumor treatment and metastasis inhibition. Although probiotic bacteria and radiotherapy alone can be effective in the treatment of different cancers, the combination of these two therapies seems to enhance therapeutic outcome and is cost-effective. Bacterial cells can act as therapeutic/gene/drug delivery vehicles as well as theranostic agents. In this communication, we reviewed current evidences, studies, suggestions, and future-based directions on combination of radiotherapy and bacteria. In another sections, an overview on tumor hypoxia, bacteria in cancer therapy, and combination of radiotherapy and bacteria is presented. A brief overview on trials and animal studies which used bacteria to protect normal tissues against radiotherapy-induced complications is also included. [ABSTRACT FROM AUTHOR]

Background: Bacterial plaques are the important etiologic factors of gingival (periodontal) diseases. It is well established that orthodontic appliances (bracket, band and arch wire) playing an important role in growth of these plaques, therefor periodontal diseases the main problems of orthodontists and these patients. Recognition of etiologic factors of these diseases is important for prophylaxis and cure performances, and the aim of present study was evaluation of clinical and microbial of gingival infections in patients treated with fixed orthodontic appliances. Materials and Methods : By refer to the orthodontic department of three dentistry clinics of Karaj city, 65 patients under fixed orthodontic treatment were selected and at third and twelfth month of treatment, after clinical parameters evaluation such as gingival index, bleeding on probing and probing depth, microbiological sampling was performed from subgingival plaques of these patients. Whole genomic DNA of the samples was extracted using a kit, and a 16S rRNA gene segment-based multiplex PCR method was used to simultaneous detection of Aggrigatibacter actinomycetemcomtans and Porphyromans gingivalis. Results: Molecular evaluation of this study showed that Aggrigatibacter actinomycetemcomtans was not present in tested samples, although transient changes in Porphyromans gingivalis frequency was reported (%20.1±0.41 (T3) and %2.7±0.16 (T12) P=0.02), also clinical evaluation revealed appearance of signs of moderate gingivitis and stability of the inflammatory lesion until termination of treatment in these patients. Conclusion: Present study showed that was no meaningful relationship between Porphyromans gingivalis and Aggrigatibacter actinomycetemcomitans to increase of chronic gingivitis in treated patients with fixed orthodontic appliances, and this long term therapy did not to prepare patients into periodontitis. [ABSTRACT FROM AUTHOR]

Purpose: Evidence suggests that changes in the composition of gut microbiota may be linked to metabolic disorders including type 2 diabetes (T2D). The present study aims to evaluate the compositional changes of the intestinal microbiota in patients with T2D as compared to healthy individuals., Methods: In this case-control study, there were 18 T2D patients and 18 healthy individuals who served as controls. To profile the gut microbiota in both groups, bacterial DNA was extracted from fecal samples and analyzed using quantitative real-time polymerase chain reaction (qPCR)., Results: The study discovered that diabetics had significantly greater frequencies of the genus Bacteroides and the phylum Bacteroidetes than did controls (P = 0.03 and P < 0.001, respectively). Conversely, the Actinobacteria and Firmicutes phyla were significantly more abundant in the controls ( P=0.01 for both). No significant differences were observed in the fecal populations of the genus Enterococcus , Clostridium clusters IV and XIVa , phylum Proteobacteria , and all bacteria between the studied groups ( P=0.88 , P=0.56 , P=0.8 , P=0.99 , and P=0.7 , respectively)., Conclusions: Our findings confirm that T2D may be associated with the gut microbiota fluctuations. These findings may be valuable for developing strategies to control or treatment T2D by restoring the intestinal microbiota through the strategic administration of specific probiotics/prebiotics and lifestyle and dietary modifications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Mycobacterium kansasii ( M. kansasii ) is a non-tuberculosis bacterium with a highly prevalent that is transferred by aerosols from water and soil resources to the respiratory system. M. kansasii is one of the main species responsible for NTM pulmonary disease., Methods: Web of Science, Scopus, and PubMed databases were systematically explored. Relevant articles from 1971 to November 2023 were reviewed. "The inclusion criteria" included patients with M. kansasii infection, treatment follow-up, and treatment outcomes. "The exclusion criteria" were clinical samples from animals, environmental samples, and other laboratory investigations., Results: 40 studies, including 1201 patients, were obtained through database search. Using the therapeutic regimens used in different studies, the therapy course for patients with M. kansasii infection ranged from 1 week to 118 months. In this study, the antibiotics prescribed in different treatment regimens for M. kansasii pulmonary infection were as follows: Rifampin, Ethambutol, Isoniazid, Clarithromycin, Streptomycin, and Pyrazinamide. Antibiotic combinations of three or four medicines, including rifampin, ethambutol, and isoniazid with or without streptomycin or pyrazinamide had the most therapeutic effect., Conclusion: The initial treatment involves rifampin, ethambutol, isoniazid, and pyridoxine, per the guidelines from the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA). Understanding the treatment plan and its outcomes is crucial for managing and determining the most effective therapy approach., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: This study investigated the effect of photodynamic therapy on chronic periodontitis patients and then evaluated the microbial, immunological, periodontal, and clinical outcomes. The significant effects of photodynamic therapy obtained by in vitro and in vivo studies have made it a popular treatment for periodontal diseases in recent years. Photodynamic therapy is a novel bactericidal strategy that is stronger, faster, and less expensive than scaling and root planing., Method: This study registered on PROSPERO (CRD42021267008) and retrieved fifty-three randomized controlled trials by searching nine databases (Medline, Embase, Scopus, Open Gray, Google Scholar, ProQuest, the Cochrane Library, Web of Science, and ClinicalTrials.gov) from 2008 to 2023. Of 721 records identified through database searches following title and full-text analysis, and excluding duplicate and irrelevant publications, 53 articles were included in this systematic review. Fifty of the 53 eligible studies fulfilled all the criteria in the Joanna Briggs Institute's (JBI's) Checklist for RCTs; the remaining articles met 9-12 criteria and were considered high quality., Results: The present study showed that photodynamic therapy in adjunct to scaling and root planing has the potential to improve periodontal parameters such as clinical attachment loss or gain, decrease in bleeding on probing, and probing pocket depth. In addition, photodynamic therapy decreases the rate of periodontal pathogens and inflammation markers, which, in turn, reduces the progression of periodontitis., Conclusion: Photodynamic therapy is considered a promising, adjunctive, and low-cost therapeutic method that is effective in tissue repair, reducing chronic periodontitis, reducing inflammation, and well-tolerated by patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mahdizade Ari, Amirmozafari, Atieh Darbandi, Afifirad, Asadollahi and Irajian.)

Legionella pneumophila can be transmitted to people, especially immunocompromised patients, via hospital water pipe systems and cause severe pneumonia. The aim of our study was to investigate the presence of major virulence factor genes, ability of biofilms formation, and correlation between presence of Legionella isolates and temperature, pH, and residual chlorine of water. Hundred water samples were collected from nine hospitals in Tehran, Iran. Temperature, pH, and residual chlorine were determined during sampling. Different virulence genes and the ability to form biofilms were subsequently analyzed among the L. pneumophila isolates. Results showed that 12 (12%) samples were positive in culture method and all of the isolates were positive as L. pneumophila species (mip). A correlation was found between Legionella culture positivity and temperature and pH of water, but there was no significant correlation between residual chlorine of water samples and the presence of Legionella. The isolation of Legionella rate in summer and spring was higher than winter and autumn. Twelve (100%) isolates were positive for mip genes, 9 (75%) for dot genes, 8 (66.66%) for hsp, 6 (50%) for lvh, and 4 (33.33%) for rtx. All of the isolates displayed strong ability for biofilm production every three days. Two of these isolates (16.6%) displayed weak ability to form biofilm on the first day of incubation. This study revealed that water sources in hospitals were colonized by virulent Legionella and should be continuously monitored to avoid elevated concentrations of Legionella with visible biofilm formation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pulmonary actinomycosis (PA) is a rare type of Actinomyces infection that can be challenging to diagnose since it often mimics lung cancer., Methods: Published case reports and case series of PA in patients with suspicion of lung cancer were considered, and data were extracted by a structured search through PubMed/Medline., Results: After analyzing Medline, 31 studies were reviewed, from which 48 cases were extracted. Europe had the highest prevalence of reported cases with 45.1%, followed by Asia (32.2%), America (19.3%), and Africa (3.2%). The average age of patients was 58.9 years, and 75% of all patients were above 50 years old. Male patients (70%) were predominantly affected by PA. The overall mortality rate was 6.25%. In only eight cases, the causative agent was reported, and Actinomyces odontolyticus was the most common isolated pathogen with three cases. Based on histopathological examination, 75% of the cases were diagnosed, and the lobectomy was performed in 10 cases, the most common surgical intervention. In 50% of the cases, the selective antibiotics were intravenous and oral penicillin, followed by amoxicillin (29.1%), amoxicillin-clavulanic acid, ampicillin, levofloxacin, and doxycycline., Conclusion: The non-specific symptoms resemble lung cancer, leading to confusion between PA and cancer in imaging scans. Radiological techniques are helpful but have limitations that can lead to unnecessary surgeries when confusing PA with lung cancer. Therefore, it is important to raise awareness about the signs and symptoms of PA and lung cancer to prevent undesirable complications and ensure appropriate treatment measures are taken., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khoshbayan, Amirmozafari and Mirkalantari.)

Background: Cancer cells have a higher demand for iron to grow and proliferate. A new complex of iron nanoparticles and thiosemicarbazones was synthesized. Confirmation tests included UV-visible, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared (FTIR), X-ray diffraction (XRD) and zeta potential., Methods: MTT assay, flow cytometry and qRT-PCR were used to investigate anti-proliferative effect, amount of apoptosis and the effect of Fe 3 O 4 @Glu/BTSC on changes in gene expression of microRNA let-7c ( let-7c ), respectively. The specifications of Fe 3 O 4 @ Glu/BTSC were confirmed at 5 nm., Results: Fe3O4@Glu/BTSC was more effective than BTSC and Fe 3 O 4 on A549 cells (IC 50 =166.77 µg/mL) but its effect on healthy cells was smaller (CC 50 =189.15 µg/mL). The drug selectivity index (SI) was calculated to be 1.13. The initial apoptosis rate was 46.33% for Fe 3 O 4 @Glu/BTSC, 28.27% for BTSC and 26.02% for Fe 3 O 4 . BTSC and BTSC@Fe 3 O 4 inhibited the cell cycle progression in the Sub-G1 and S phases. let-7c expression was 6.9 times higher in treated cells compared to the control group. The expression rate was 2.2 with BTSC compared to the control group and 1.6 times for Fe 3 O 4 ., Conclusion: Fe 3 O 4 @Glu/BTSC has proper anti-proliferative effects against lung cancer cells by increasing the expression of let-7c and inhibiting the cell cycle with the apoptosis activation pathway., (© 2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: This case-control study was designed to compare the composition of the predominant oral bacterial microbiome in Alzheimer's disease (AD) and control group., Subject: A total of 30 adult participants (15 AD and 15 healthy individuals) were entered in this study. The composition of oral bacterial microbiome was examined by quantitative real-time polymerase chain reaction (qPCR) using bacterial 16S rDNA gene. The levels of systemic inflammatory cytokines in both groups were assessed using enzyme-linked immunosorbent assays (ELISA)., Results: The loads of Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia were significantly more abundant in the AD compared to the control group (p < 0.05). Although Aggregatibacter actinomycetemcomitans and Streptococcus mutans were relatively frequent in the AD group, no significance difference was observed in their copy number between two groups. Although the concentrations of IL-1, IL-6, and TNF-α were higher in the AD group, there was a significant difference in their levels between the two groups (p < 0.05). Finally, there was a significant relationship between increased number of pathogenic bacteria in oral microbiome and higher concentration of cytokines in patient's blood., Conclusion: Our knowledge of oral microbiome and its exact association with AD is rather limited; our study showed a significant association between changes in oral microbiome bacteria, increased inflammatory cytokines, and AD., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Problem: Enterococcus faecalis is a common microbial semen contaminant. Although virulence factors and biofilm formation have often been analyzed in Enterococcus spp., there is little information about these features in isolates obtained from the genitourinary tract. This study was intended to characterize and determine the relationship between biofilm-forming ability and the presence of E. faecalis virulence factors isolated from human semen., Method of Study: A total of 32 patients diagnosed with primary infertility and 28 healthy men were included in the study. Semen analyses were performed according to the WHO guidelines. PCR reactions were applied for the detection of ace, esp, efeA, gelE, asa1, and cylA genes. Microtiter plate assay, via measurement of OD 560, was used to measure the biofilm-forming ability of the isolates., Results: Sixty E. faecalis isolates from semen of infertile and fertile men were characterized by phenotypic and genotypic methods. The prevalence of ace, esp, efeA, gelE, asa1 and cylA were reported to be 81.3%/100.0%, 81.3%/89.3%, 81.3%/85.7%, 71.9%/53.6%, 8.8%/75.0%, and 62.5%/67.9% in infertile/fertile groups; respectively. Strong, weak, and non-biofilm reactions were reported to be 50.0%/21.4%, 40.6%/64.3%, and 9.4%/14.3% in infertile and fertile groups; respectively., Conclusions: There was a significant relationship between fertility and weak biofilm reaction and also between biofilm formation and possession of the esp gene (P < .05). It could be speculated that colonization with E. faecalis with a strong ability for biofilm formation could become a potential threat to men's fertility., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Objective: This study aims to isolate a lytic bacteriophage against planktonic  Enterococcus faecalis V583 culture and evaluate its ability to disrupt and inhibit biofilm., Methods: An anti- E. faecalis phage was isolated from sewage and visualized by electron microscopy, the vB&#95;EfsS&#95;V583 (V583) host range was determined by spot test on 13 E. faecalis clinical strains. Inhibition and degradation experiments were designed to investigate the effect of phage on biofilm. In the inhibition and degradation assay, biofilms were formed in the presence and absence of phage, respectively. Finally, crystal violet method tested the effect of phage on biofilm., Results: Phage V583 belongs to the Siphoviridae family and can infect all E. faecalis strains. Antibacterial activity has been shown to degrade and inhibit biofilm produced by V583. The study results showed that phage v583 is more efficient in biofilm inhibition than biofilm degradation. In both assays, phage-treated wells' absorption is less than untreated wells. These results were confirmed by Colony-forming unit reduction in the treated biofilm., Conclusion: The anti-biofilm activity showed that phage therapy using phage V583 might be an alternative tool to remove E. faecalis biofilms., Competing Interests: The authors declared no conflict of interests.

Background and Objectives: Due to the reduced susceptibility of clinical Clostridioides difficile strains in hospitals to various antimicrobial agents, the importance of antimicrobial susceptibility testing (ASTs) has increased. This study aimed to investigate the toxin gene profiles and the antimicrobial resistance of C. difficile isolated from hospitalized patients suspected of having Clostridioides difficile infection (CDI) in Tehran, Iran., Materials and Methods: The stool samples were obtained from a hospitalized patients. The samples were shocked by alcohol and the patients cultured on cycloserine-cefoxitin-fructose agar in anaerobic Conditions. Toxin assay was performed for detection of toxinogenic isolates. An antibiotic susceptibility test was done. Furthermore, their genome was extracted for PCR to confirm C. difficile and detect toxin gene profile., Results: Toxigenic C. difficile were identified in 21 of the 185 stool samples (11.3%). PCR detected seven toxin gene profiles; the highest prevalence was related to tcdA + B + , cdtA + B - toxin gene profile (57.1%). There were 14.3% and 28.6% resistant rates of the isolates towards vancomycin and metronidazole with the toxin gene profiles; tcdA + B + , cdtA ± B + ; and tc- dA + B - , cdtA - B + . All resistant isolates to moxifloxacin, clindamycin, and tetracycline were belonged to the toxin gene profiles; tcdA + B + , cdtA + B + ; tcdA + B + , cdtA + B - , and tcdA - B + , cdtA+B - ., Conclusion: Relative high resistance was detected towards metronidazole and vancomycin, although, still have acceptable activity for CDI treatment. However, a proper plan for the use of antibiotics and more regular screening of C. difficile antibiotic resistance seems necessary., (Copyright © 2021 The Authors. Published by Tehran University of Medical Sciences.)

Background and Objectives: An important leading cause of the emergence of vancomycin-resistant enterococci, especially Enterococcus faecium , is the inefficiency of antibiotics in the elimination of drug-resistant pathogens. Consequently, the need for alternative treatments is more necessary than ever., Materials and Methods: A highly effective bacteriophage against vancomycin-resistant E. faecium called vB-EfmS-S2 was isolated from hospital sewage. The biological properties of phage S2 and its effect on biofilm structures were determined., Results: Phage S2 was specifically capable of lysing a wide range of clinical E. faecium isolates. According to Electron microscopy observations, the phage S2 belonged to the Siphoviridea family. Suitable pH spectra for phage survival was 5-11, at which the phage showed 100% activity. The optimal temperature for phage growth was 30-45°C, with the highest growth at 37°C. Based on one-step growth curve results, the latent period of phage S2 was 14 min with a burst size of 200 PFU/ml. The phage S2 was also able to tolerate bile at concentrations of 1 and 2% and required Mg2+ for an effective infection cycle. Biofilms were significantly inhibited and disrupted in the presence of the phage., Conclusion: According to the results, phage S2 could potentially be an alternative for the elimination and control of vancomycin-resistant E. faecium biofilm., (Copyright © 2021 The Authors. Published by Tehran University of Medical Sciences.)

Background: One of the causes of male infertility is Genital tract infections (GTI). Considering the importance of GTI, widespread recognition of them seems necessary. we aimed to characterize and compare semen microbial populations in fertile and infertile men who referred to an infertility clinic in Yazd, Iran., Methods: Semen samples were collected from two groups of fertile (268) and infertile (210) men. Sperm analysis (concentration, morphology, viability and motility parameters) were performed according to the World Health Organization (WHO) 2010 guidelines laboratory manual. Bacterial isolation was performed in Sheep Blood Agar and Eosin Methylene Blue (EMB) agar plates. For PCR, samples were analyzed with genus specific primers., Results: All semen characteristics were poor in the infertile group compared to those in the fertile men (p-value< 0.05). Enterococcus spp. (18.7%, 17.1%; p= 0.814), E. coli (7.9%, 11.4%; p= 0.486), Staphylococcus aureus (6.4%, 2.9%; p= 0.398) and Proteus mirabilis (0%, 2.9%; p= 0.002) were the most common agents, respectively. Also, the results obtained from PCR were confirmed using culture-base method., Conclusion: Proteus mirabilis contamination was identified in the infertile group. While no significant association was observed between male infertility and semen microbial populations, p. mirabilis may be the leading cause of reproduction impairment in men.

Background: Bacterial spores are among the most efficient vaccine delivery vehicles. Because of their safety and efficacy, Bacillus subtilis spores are increasingly used in this regard. The negatively charged surfaces of the spores allow antigens to be adsorbed onto these structures. In this study, a candidate vaccine against Salmonella enterica serovar Typhi was adsorbed onto B. subtilis spores and the immunogenicity of the formulation was investigated in BALB/c mice., Methods: This work was performed during 2018-2019 in Islamic Azad University of Lahijan. FliC protein was recombinantly expressed in E. coli BL21 (DE3) cells and purified by affinity chromatography. On the other hand, B. subtilis strain PY79 (ATCC1609) was cultured in DSM medium and after the sporulation, FliC protein was adsorbed onto the spores in three different pH values (4, 7 and 10) and the adsorption was verified using dot-blot assay. FliC-adsorbed spores were then administered to BALB/c mice through the subcutaneous route. Mice immunization was evaluated by serum IgG assessment and challenge study., Results: FliC protein was successfully expressed and purified. Sporulation was controlled by phase-contrast microscopy. Serum IgG assay showed significant stimulation of the mice's humoral immune system. Immunized mice were able to resist bacterial infection., Conclusion: The results showed the efficiency of spores as natural adjuvants for the stimulation of mice immune system. The formulation can be exploited for the delivery of recombinant vaccines against bacterial pathogens., Competing Interests: Conflict of interests There is no potential conflict of interests relevant to this paper., (Copyright © 2021 Ghorbani et al. Published by Tehran University of Medical Sciences.)

Bacterial infections are a serious risk to human health, and therefore techniques for early detection of infectious foci need to be further developed to begin treatment quickly and achieve better results. Antimicrobial peptides labeled with gamma-emission radio nuclides are important diagnostic radiotracers in nuclear medicine. This study was conducted to evaluate the potential of a 99m Tc-labeled MicrocinJ25 (MccJ25) antimicrobial peptide analog for early detection of infection. For this purpose, a HYNIC conjugated cyclic peptide derivative based on the primary structure of MccJ25 peptide was prepared and labeled by 99m Tc with tricine and EDDA as coligands. The [ 99m Tc-HYNIC/EDDA]-MccJ25 peptide analog showed high radiochemical purity (˃90% (n = 5)) which was stable up to 24 hr after labeling. The radiotracer showed specific uptake to the Escherichia coli (E. coli) bacterial (40.45 ± 5.21%) at 1 hr incubation. High kidneys uptake of radioactivity (4.71 ± 0.84% and 3.76 ± 0.45% ID/g at 1 and 4 hr after injection respectively) demonstrates that most of the whole body clearance was proceeded via the urinary system. Significant radioactivity uptake (1.71 ± 0.34%ID/g) was observed in thigh muscle of mouse with E. coli induced infection at 1 hr after injection. In the blocking test, due to the significant decrease of radioactivity uptake in the infection site (0.62 ± 0.21%ID/g after 1 hr), the specificity of infection uptake was reviled. Despite the high activity of the bladder due to urinary excretion, the infected area was somewhat visible. Hence, the results indicate the potential of this new radiotracer to be used as a diagnostic agent in E. coli infections., (© 2020 John Wiley & Sons A/S.)

Background and Objectives: Acinetobacter baumannii is recognized as an important pathogen responsible for serious infections causing episodes of hospital infection. Carbon nanotubes (CNTs) have recently emerged as superior materials against antibiotic-resistant bacteria. In this study, a new chemical compound was designed in order to combat A. baumannii infections. Subsequently, the effect of this novel carbon nanotube coated with an antibacterial compound on Extensively Drug-Resistant (XDR), Multidrug-Resistant (MDR) and Pan-Drug-Resistance (PDR) strains of A. baumannii was investigated., Materials and Methods: A total of 122 clinical isolates of A. baumannii were cultured from burn patients and their susceptibility to antibiotics were checked using disk diffusion method and Minimum inhibitory concentration. Antimicrobial effects of the coated carbon nanotube were evaluated on XDR, MDR and PDR isolates of A. baumannii . Cell viability was determined using tetrazolium reduction assay (MTT) on human fibroblast cell line (HDFa). Wound healing processes were assessed by quantitative polymerase chain reaction., Results: Of the 50 A. baumannii isolates, 38 (76%) were found to be MDR and 12 (24%) were XDR. No PDR strains were detected. Results indicated that the carbon nanotube combined with mercury had antibacterial effect against different A. baumannii species and it also was able to increase the expression of epidermal growth factor, platelet-derived growth factor and vascular endothelial growth factor A mRNA levels which are involved in wound healing., Conclusion: The engineered carbon nanotube compound can potentially be used for treatment of burn related infections. This can potentially give clinicians a new tool for treating A. baumannii infections., (Copyright © 2021 The Authors. Published by Tehran University of Medical Sciences.)

Pseudomonas aeruginosa is one of the most common reasons for nosocomial infections. Given the high morbidity and mortality, as well as the cost of management, particularly in developing countries, burn injuries are considered important health concerns. Owing to the increased rate of resistance against antibiotics, this study aimed to isolate Pseudomonas aeruginosa strains from burn patient's wounds by analyzing antibiotic susceptibility and genetic profiling. In this regard, we explored the relationship between the nucleotide sequence and antibiotic susceptibility. In this cross-sectional study, 107 isolates of P. aeruginosa were collected from a major burn center in Tehran, Iran. The isolates were characterized with standard biochemical tests and examined by applying the Disk Diffusion method to find the patterns of sensitivity, and their genetic relationship was revealed by RAPD-PCR method. According to the antibiogram results, most of the isolates were resistant to 3 or more antibiotics tested and the most sensitivity was related to the Colistin antibiotic. RAPD-PCR method revealed a high polymorphism among P. aeruginosa isolates in Tehran. There was no significant association between the genotype groups and antibiotic susceptibility profiles. We evaluated the pattern of resistance to pathogenic organisms and identified multi-drug resistant organisms. Currently, Colistin antibiotic is the most suitable treatment option for burned patients. RAPD-PCR is a genotyping method with high efficiency for typing and categorizing different isolates of MDR- P. aeruginosa ., (© 2020 Published by Elsevier Ltd.)

Background: Probiotics have been associated with many beneficial effects in human digestive physiology. The aim of this study was to evaluate the effect of improved formulation of chitosan-alginate microcapsules of Bifidobacterium strains on serum triglycerides, cholesterol, HDL, and LDL in mice., Methods: Five approved probiotic strains of Bifidobacterium were tested for anti-proliferative effect and interleukin-8 induction on HT-29 cell lines. Bifidobacterium strains plus five approved Lactobacillus were encapsulated in chitosan-alginate microcapsules and tested for its survival in simulated gastrointestinal conditions. These microcapsules were administered to 4 groups of mice (including 1. Bif (Bifidobacterium strains), 2. Lac (Lactobacillus strains), 3. Bif-Lac (Bifidobacterium plus Lactobacillus strains) and 4. Control) for 8 days. At eighth day, the blood of mice were taken and serum levels of triglycerides, cholesterol, HDL, and LDL of them were determined., Results: All of the Bifidobacterium strains significantly (P < 0.001) reduced secretion of IL-8 in HT-29 cells as well as maximum antiproliferative effects (P < 0.001). In addition, all microcapsules showed impressive survival rate in bile (>%94.1) and gastrointestinal (>%78.28) conditions (P < 0.05). Only Bif-Lac group displayed significantly lower serum cholesterol and LDL levels than control group (P < 0.05). Besides, all groups indicate statistically significant weight loss of mice during the 8 days in comparison with the control group (P < 0.05)., Conclusion: The results of this study showed that the microencapsulated probiotics with alginate and chitosan had an effective mean of delivery of viable bacterial cells and non-pharmacological interventions use to reduce serum cholesterol and LDL levels in in-vivo condition., (Copyright © 2020. Published by Elsevier Ltd.)

Background: In Iran, zoonotic and anthroponotic cutaneous leishmaniasis (CL) are caused by Leishmania major and L. tropica respectively. Despite extensive studies, no effective therapies have ever been reported for CL. The main objective of this research was to determine and compare the three different protocols for treatment of CL patients referring to Skin Diseases and Leishmaniasis Research Center (SDLRC), affiliated to Isfahan University of Medical Sciences, Isfahan, Iran from September 2017 to October 2018., Methods: In a randomized controlled parallel groups clinical trial, 150 selected CL patients who met our inclusion criteria were randomly assigned to one of the three therapy groups: A, intra-lesional glucantime plus 50% trichloroacetic acid (TCA), B, intralesional glucantime and C, systemic glucantime. All patients in the three groups received the complete course of treatment and were followed for 6 months. To identify the etiologic agents, smears from their lesions were prepared and PCR-RFLP was used after parasite culture. Also, clinical characteristics, history of previous involvement, endemic emigration and demographic data were collected., Results: The results showed that the mean value of healing period was 53.12 ± 25.88 (median: 45, IQR: Q1 = 30-Q3 = 77) days in group A, 57.22 ± 44.02 (median: 42.5, IQR: Q1 = 30-Q3 = 60) days in group B, and 73.56 ± 41.08 (median: 71, IQR: Q1 = 45-Q3 = 90) days in group C; the observed differences were statistically significant ( P =0.024). There was a significant difference between group A and group C ( P = 0.049), and between group B and group C ( P = 0.047) in terms of mean healing period. Finally, complete recovery rates of 80%, 62% and 42% were shown in the three medicinal groups of A, B and C, respectively ( P = 0.022)., Conclusion: In this study, the average duration of lesion healing among the three groups was the shortest in patients with IL glucantime plus 50% TCA treatment regimen. Also, the use of 50% TCA in patients suffering from CL was associated with a significant improvement in the depth of scars, the time and the percentage of recovery, and the low cost of this agent in the treatment of CL., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Strongyloidiasis is a public health concern in northern regions of Iran, caused by Strongyloides stercoralis . Auto-infection cycle can be resulted in high parasitic load, especially in immunocompromised hosts. Because of low sensitivity of stool culture and stool-based microscopy techniques, detection of antibodies in patient's sera can be an alternative diagnostic technique for detection of the nematode. In the present study, as the first step of the development of an ELISA kit for the detection of antibodies against the nematode, IgG4 immunoreactive protein (NIE) was expressed in Escherichia coli expression system, purified and verified., Methods: The NIE gene sequence was retrieved from the GenBank. This sequence was codon-optimized for the expression in E. coli BL21 (DE3). The sequence was inserted into the expression vector pET-30b (+). The recombinant vector was then transferred into competent E. coli BL21 (DE3). Transformed colonies were selected and verified by colony PCR. NIE gene expression was induced with IPTG induction. The protein production was evaluated by SDS-PAGE and verified using Western blotting., Results: The codon-optimized NIE gene had required parameters for expression in E. coli . NIE protein was proved and verified by SDS-PAGE and Western blotting., Conclusion: NIE recombinant protein was successfully expressed in E. coli expression system in appropriate amounts. The recombinant protein can be used for developing ELISA kit in diagnosis of S. stercoralis., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright© Iranian Society of Parasitology & Tehran University of Medical Sciences.)

Background: Pseudomonas aeruginosa is an opportunistic human pathogen that causes severe acute and chronic nosocomial infections, especially in immunocompromised burn patients. and can lead to severe mortality and morbidity. The emergence of antibiotic resistant P. aeruginosa infections has created significant challenges in treating these patients. A potential alternative treatment for antibiotic resistant pathogens includes the use of carbon nanotubes (CNTs), which have received considerable attention due to their potent antibacterial activity. The aim of this study was to construct a novel CNT containing an anti-bacterial chemical component to effectively combat drug resistant P. aeruginosa infections., Methods: In this study, a novel chemical component was synthesized and coated the CNT. The antimicrobial effects were then evaluated on MDR, XDR, and PDR strains of P. aeruginosa isolated from burn patients. Antibiotic susceptibility was evaluated using the disk diffusion test and minimum inhibitory concentration (MIC) testing. In order to determine the potential cytotoxicity, an MTT assay was performed on Human Dermal Fibroblasts. The effect of treatment on the expression of wound healing genes was analyzed via qRT-PCR., Results: Experimental data indicates that our CNT coated chemical compound had antibacterial properties, negligible cytotoxicity, and could accelerate the wound healing process., Conclusion: Given the antibacterial properties of our CNT chemical compound, it has the potential to treat and reduce the occurrence of multi-drug resistant P. aeruginosa burn wound infections and aid in wound healing by turning on genes (VEGFA, EGF and PDEGF) involved in the wound healing process.

Background: The presence and diversity of Staphylococcus species and their enterotoxin-encoding genes in foodstuffs have not been comprehensively studied in some developing countries. This study aimed to assess the frequency of Staphylococcus spp. and their related virulence factors in foodstuffs in Isfahan, Iran., Methods: Overall, 139 foodstuff samples, collected from Isfahan City (center of Iran) from Sep 2015 to Oct 2016, were processed for the presence of Staphylococcus spp. using standard bacteriological procedures and sequence analysis of 16S rRNA gene. Antimicrobial susceptibilities and prevalence of mecA and toxin-encoded genes ( sea , seb , sed , see and tsst 1 ) were tested for all of the Staphylococcal isolates., Results: Forty-four Gram-positive cocci were recovered from 139 dairy and meat samples . The most prevalent species were S. vitulinus 25.0% (11/44) and S. aureus 20.5% (9/44); respectively. The most prevalent antimicrobial resistance was noted towards penicillin, cefoxitin and tetracycline. The sec , sea , see and tsst1 genes were found in 19%, 9.5%, 3.5%, and 3.5% of the isolates, respectively., Conclusion: Numerous virulence factors were detected in different Staphylococcus spp. isolated from foodstuffs, more attention should be paid to the presence of the bacteria. Proper hygienic and management practices should be considered in order to increase food safety and prevent extra treatment costs., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright© Iranian Public Health Association & Tehran University of Medical Sciences.)

Eradication failure of Helicobacter pylori infection could play a causal role in progression of gastric disorders. In this study, infection with H. pylori was followed in gastric biopsies of symptomatic adult patients at two phases during 1-year period. Analyses were done to show association of therapeutic regimens with the refractory infection, changes in sequence types (STs) and minimum inhibitory concentration (MIC) values, and progression of histopathological changes. Infection with H. pylori was confirmed in 32.3% (57/170) of the patients. Persistent infection with H. pylori was confirmed in 14 out of the 25 patients (56%) who participated at the second phase of the study. A difference between primary and secondary resistance rates to clarithromycin (49% vs 64.3%), metronidazole (76.36% vs 100%), and ciprofloxacin (45% vs 57.1%) was detected. Although the re-emerged strains in patients with refractory infection did not show alteration in STs, their MIC 50 values showed twofold increases for clarithromycin and ciprofloxacin. While ciprofloxacin containing regimens were more successful, failure of metronidazole containing regimens was detected in 77% of the patients. Consequently, inappropriate medication has an impact on refractory H. pylori infection, which could cause to a rise in resistance levels to antibiotics and progression of pathological disorders., (© 2019 APMIS. Published by John Wiley & Sons Ltd.)

Antimicrobial peptides (AMPs) or host defense peptides (HDPs) are vital components of human innate defense system targeting human-related bacteria. Many bacteria have various mechanisms interfering with AMP activity, causing resistance to AMPs. Since AMPs are considered as potential novel antimicrobial drugs, understanding the mechanisms of bacterial resistance to direct killing of AMPs is of great significance. In this review, a comparative overview of bacterial strategies for resistance to direct killing of various AMPs is presented. Such strategies include bacterial cell envelope modification, AMP degradation, sequestration, expelling, and capsule., (© 2019 European Peptide Society and John Wiley & Sons, Ltd.)

Objectives: Clostridium difficile (C. difficile) is the main causative agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis. The accumulation of antimicrobial resistance in C. difficile strains can drive C. difficile infection (CDI) epidemiology. This study was undertaken to evaluate the antimicrobial resistance patterns of toxigenic C. difficile isolates cultured from diarrhoeal stool samples of hospitalised patients with suspected CDI in three tertiary care hospitals in Tehran, Iran., Methods: Two hundred and fifty diarrhoeal stool samples were investigated by toxigenic culture using cycloserine-cefoxitin-fructose agar and the VERO cell line. Antimicrobial susceptibility to metronidazole, vancomycin, clindamycin, tetracycline, and moxifloxacin was performed by disk diffusion and Etest methods on Brucella Blood Agar supplemented with hemin and vitamin K., Results: Thirty-five stool samples (14.0%) proved positive using C. difficile toxigenic culture. According to Clinical and Laboratory Standards Institute breakpoints, the following resistance was identified in C. difficile isolates: metronidazole (2 of 35); moxifloxacin (7 of 35); clindamycin (18 of 35); and tetracycline (5 of 35). Using European Committee on Antimicrobial Susceptibility Testing breakpoints, three of 35 isolates showed reduced-susceptibility for vancomycin and 14 of 35 for metronidazole. In addition, the results showed a good correlation between the inhibition zone diameter (disk diffusion) and MIC values (Etest); Pearson correlation coefficient 0.7400.95 (P< 0.001)., Conclusions: Multidrug resistance was observed in Iranian clinical toxigenic C. difficile isolates, including reduced susceptibility to first-line CDI treatment drugs. In addition, disk diffusion can be used as a cost-effective option for the antimicrobial susceptibility testing of C. difficile isolates., (Copyright © 2019 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: Gardnerella vaginalis is considered as the predominant microorganism found in bacterial vaginosis (BV). The aim of this study was to evaluate the prevalence of virulence factors in G. vaginalis associated with BV or non-BV cases and their correlations with this disorder. Methods: A total of 102 vaginal specimens were collected from patients during their visit to Akbar Abadi hospital in Tehran, Iran. Bacterial vaginosis was determined by Nugent score and Amsel's criteria. Polymerase chain reaction (PCR) was used for the detection of G. vaginalis 16S rRNA, vaginolysin, sialidase and phospholipase genes. To evaluate the association between the presence of vly, pho , and sld genes and BV. Pearson Chi-square test was applied using SPSS software. P-value ≤0.05 was considered as significant. Results: Totally, 27.4% of the patients were suffering from BV. Gardnerella vaginalis was found in 100% women with BV and in 56.7% women with normal vaginal discharge. The prevalence of vly, sld and pho genes in BV-associated G. vaginalis was 10 (35.7%) (95% CI [0.18, 0.53]), 19 (67.8%) (95% CI [0.51, 0.85]) and 6 (21.4%) (95% CI [0.06, 0.37]), respectively. The prevalence of the aforementioned genes in non-BV associated G. vaginalis was 20 (47.6%) (95% CI [0.33, 0.63]), 28 (66.6%) (95% CI [0.52, 0.81]), and 5 (11.9%) (95% CI [0.02, 0.22]), respectively. Our results showed no statistically significant association between the presence of the virulence genes and BV associatedness of this microorganism. Conclusion: Our results showed the presence of G. vaginalis in all BV patients and relatively high prevalence in healthy individuals. The prevalence rates of the three virulence genes were different in BV and non-BV associated G. vaginalis ; however, the differences were not statistically significant., (© 2019 Iran University of Medical Sciences.)

Background and Objectives: Klebsiella pneumoniae isolates that produce K. pneumoniae carbapenemase (KPC) have become a grave concern for the treatment of infections. KPC-producing strains are not only able to hydrolyze carbapenems but are also resistant to a variety of β-lactam and non-β-lactam antibiotics. The present study evaluated the prevalence of bla KPC in K. pneumoniae infections and determined the antimicrobial susceptibility of the isolates., Materials and Methods: The K. pneumoniae isolates were identified by biochemical tests and confirmed by genotyping. The modified Hodge test (MHT) was performed to detect carbapenemases, and antimicrobial susceptibility was determined for all isolates by the disc diffusion method. Also, for MHT-positive isolates, supposed to carbapenemases isolates, broth microdilution method was used to measure the minimum inhibitory concentrations (MICs) of meropenem and colistin., Results: The bla KPC genotypic evaluation revealed that only 5 of 96 isolates carried bla KPC genes. Antimicrobial pattern showed that isolates carrying bla KPC were resistant to cefepime, ticarcillin/tazobactam, and aztreonam discs. Also, results of broth microdilution method showed that KPC-producing K. pneumoniae was resistant to meropenem and colistin, according to the CLSI and EUCAST., Conclusion: In this study nearly half the isolates showed carbapenemase activity as shown by MHT results, but only few of them were carrying bla KPC . Thus bla KPC gene is not the main cause of resistance spread to carbapenems in Isfahan, Iran., (Copyright© 2019 Iranian Neuroscience Society.)