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Objective(s): Pseudomonas aeruginosa is an opportunistic pathogen that is an important cause of nosocomial infections. This bacterium produces various virulence factors, among which exotoxin A is significantly involved in mortality and morbidity. In this study, we evaluated the immunogenicity of native exotoxin A extracted from the P. aeruginosa and its conjugation with gold nanoparticles in the animal model. Materials and Methods: Exotoxin A was first extracted and purified from the culture medium of P. aeruginosa PAO1 by selective precipitation and dialysis. The gold nanoparticles were prepared using the Turkevich method and conjugated to the prepared exotoxin A by electrostatic force. The size and conjugation were confirmed using electron microscopy and Fourier transform infrared spectrometry (FTIR), respectively. The immunogenicity of prepared ExoA-gold nanoparticles was investigated in the mice model. Results: The results indicated that nano-gold particles can be conjugated to the native exotoxin A with high efficiency. Immunogenicity investigation demonstrated that antibody titers produced against native exotoxin A and its conjugate to nano-gold particles are significant in a mouse model (P

Acinetobacter baumannii is a nosocomial pathogen and gram-negative coccobacillus that is responsible for opportunistic infections, pneumonia, and infections of the urinary tract, bloodstream, skin, and soft tissue. This bacterium poses a major public health problem due to inducing resistance to several drugs, isolates, multidrug treatment, and occasionally pan drugs. Drug resistance is not only a major concern caused by A. baumannii but also is considered as the main challenge in many other pathogens. Several factors such as the efflux pump are associated with antibiotic resistance, biofilm production, and genetic mutations. In this review, A. baumannii is introduced in then some of the practical works conducted on the existing efflux pump are reviewed. The importance of the efflux pump is considered in this paper in relation to the antibiotic resistance and mechanisms developed for the inhibition of these pumps as well.

Pourya Gholizadeh,1,2 Şükran Köse,3 Sounkalo Dao,4 Khudaverdi Ganbarov,5 Asghar Tanomand,6 Tuba Dal,7 Mohammad Aghazadeh,8 Reza Ghotaslou,8 Mohammad Ahangarzadeh Rezaee,8 Bahman Yousefi,8 Hossein Samadi Kafil2,9 1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 2Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 3Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Tepecik Training and Research Hospital, Ä°zmir, Turkey; 4Faculté de Médecine, de Pharmacie et d’Odonto-Stomatologie (FMPOS), University of Bamako, Bamako, Mali; 5Department of Microbiology, Baku State University, Baku, Republic of Azerbaijan; 6Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran; 7Department of Clinical Microbiology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey; 8Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 9Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranCorrespondence: Hossein Samadi KafilDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranTel +98 9127184735Fax +98 4133364661Email Kafilhs@tbzmed.ac.irAbstract: Rapid emergence of antibiotic-resistant bacteria has made it harder for us to combat infectious diseases and to develop new antibiotics. The clustered regularly interspaced short palindromic repeats –CRISPR-associated (CRISPR-Cas) system, as a bacterial adaptive immune system, is recognized as one of the new strategies for controlling antibiotic-resistant strains. The programmable Cas nuclease of this system used against bacterial genomic sequences could be lethal or could help reduce resistance of bacteria to antibiotics. Therefore, this study aims to review using the CRISPR-Cas system to promote sensitizing bacteria to antibiotics. We envision that CRISPR-Cas approaches may open novel ways for the development of smart antibiotics, which could eliminate multidrug-resistant (MDR) pathogens and differentiate between beneficial and pathogenic microorganisms. These systems can be exploited to quantitatively and selectively eliminate individual bacterial strains based on a sequence-specific manner, creating opportunities in the treatment of MDR infections, the study of microbial consortia, and the control of industrial fermentation.Keywords: antibiotic-resistant bacteria, CRISPR-Cas system, sequence-specific manner, resensitization, genome editing

Raman Ahmadi,1 Asghar Tanomand,2 Fahimeh Kazeminava,1 Fadhil S Kamounah,3 Ali Ayaseh,4 Khudaverdi Ganbarov,5 Mehdi Yousefi,6 Adib Katourani,1 Bahman Yousefi,7 Hossein Samadi Kafil11Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran; 3Department of Chemistry, University of Copenhagen, DK- 2100 Copenhagen. Denmark; 4Department of Food Science and Technology, University of Tabriz, Tabriz, Iran; 5Department of Microbiology, Baku State University, Baku, Azerbaijan; 6Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 7Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranObjective: The microbial, physico-chemical and optical corruptions threaten a variety of foods and drugs and consequently the human biological safety and its accessible resources. The humanbeing’s tendency towards bio-based materials and natural plant-extracts led to an increase in the usage of antimicrobial biocomposites based on medicinal herbs. Miswak (Salvadora persica L.) extract (SPE) has been proved effective for its antimicrobial and other biological activities. Therefore, in this study, titanium dioxide (TiO2) nanoparticles (TONP) and SPE were applied to fabricate antimicrobial carboxymethyl cellulose (Na-CMC) based bio-nanocomposites which would simultaneously promote some thermo-physical and barrier properties.Methods: CMC-neat film (C1), CMC/TONP-2% (C2) and CMC/TONP-2% with 150, 300 and 450 mg/mL SPE (SPE150, SPE30 and SPE450, respectively) were fabricated. The physical and mechanical properties; elemental mapping analysis (MAP), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA-DTG); fourier transform infrared (FTIR), energy-dispersive X-ray (EDX) and UV-vis spectroscopies were done to further validate the results.Results: Addition of TONP (2%) improved the blocking of UV light at 280 nm while SPE-containing nanocomposites completely blocked it. FTIR, XRD and SEM confirmed the formation of homogeneous films and high miscibility of applied materials. TONP led to an increase in Young’s modulus (YM) and stress at break (SB) while SPE decreased them and enhanced the elongation to break (EB) (flexibility) of the active nanocomposites. Compared to CMC-film, the thermo-gravimetric analysis (TGA-DTG) showed a higher thermal stability for CMC/TONP and CMC/TONP/SPE nanocomposites. The EDX spectroscopy and elemental mapping analysis (MAP) proved the existence and well-distributedness of Na, K, Cl, S, Ti, F and N elements in SPE-activated nanocomposites. The pure SPE and SPE-activated nanocomposites showed a favorable antimicrobial activity against both gram-positive (Staphylococcus aureus) and negative (Escherichia coli) bacteria.Conclusion: The CMC-TiO2-SPE nanocomposites were homogeneously produced. Combination of TiO2 nanoparticles and dose-dependent SPE led to an improvement of thermal stability, and high potential in antimicrobial and UV-barrier properties. These results can generally highlight the role of the fabricated antimicrobial bio-nanocomposites as a based for different applications especially in food/drug packaging or coating.Keywords: antimicrobial biomaterials, biopolymeric nanocomposite, carboxymethyl cellulose, Miswak (Salvadora persica L.), titanium dioxide, food packaging

Zahra Aghapour,1,2 Pourya Gholizadeh,3 Khudaverdi Ganbarov,4 Abed Zahedi Bialvaei,5 Suhad Saad Mahmood,6 Asghar Tanomand,7 Mehdi Yousefi,8 Mohammad Asgharzadeh,9 Bahman Yousefi,9 Hossein Samadi Kafil11Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 3Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 4Department of Microbiology, Baku State University, Baku, Azerbaijan; 5Department of Microbiology, Iran University of Medical Sciences, Tehran, Iran; 6Department of Biotechnology, College of Science, University of Baghdad, Baghdad, Iraq; 7Department of Microbiology, Maragheh University of Medical Sciences, Maragheh, Iran; 8Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 9Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, IranAbstract: Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.Keywords: colistin, Enterobacteriaceae, two-component system, lipid A, mcr genes

Aims: To determine the inhibitory effect of oral Lactobacillus against bacterial pathogens and investigate correlation between presence of Lactobacillus strains and health promotion. Method: One hundred saliva samples were collected from oral cavity of domestic dairy consumers and were investigated for the isolation and identification of Lactobacillus strain by conventional culture and sequencing of 16SrRNA. Furthermore, well diffusion assay was performed to determination of antibacterial activity of Lactobacillus strains against bacterial pathogens including Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis and Enterococcus faecium. Finally, association between health condition and isolation of Lactobacillus were investigated and obtained data using questionary form were analysed by chi-square test. Results: Thirty Lactobacillus strains recovered from 100 hundred saliva samples. The most common isolated strain was L. gasseri (n=18) and followed by L. vaginalis (n=3) and L. salivarius (n=3). All Lactobacillus strains demonstrated antibacterial activity against at least one of the investigated pathogens. However, the strongest results were obtained by L. vaginalis against K. pneumonia. The correlation between the presence of thirty Lactobacillus strains and health promotion not found. However, only L. gasseri species has significant positive impact on health in their hosts (P < 0.05). Conclusion: Only some Lactobacillus species have a positive impact on health promotion. Despite of weak activity against the investigated pathogens, L. gasseri has a positive impact on the mental problem (intense anger and depression) of their hosts., Objetivos: Determinar el efecto inhibidor del Lactobacillus aislado de la cavidad oral contra patógenos bacterianos e investigar la correlación entre la presencia de cepas de Lactobacillus y la promoción de la salud. Método: se recolectaron cien muestras de saliva de la cavidad oral de consumidores de productos lácteos y se investigó el aislamiento e identificación de la cepa de Lactobacillus mediante cultivo convencional y secuenciación de 16SrRNA. Además, se realizó un ensayo de difusión en pocillos para determinar la actividad antibacteriana de las cepas de Lactobacillus contra patógenos bacterianos que incluyen Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis y Enterococcus faecium. Finalmente, se investigó la asociación entre el estado de salud y el aislamiento de Lactobacillus y se obtuvieron los datos utilizando el cuestionario mediante la prueba de chi-cuadrado. Resultados: Se aislaron treinta cepas de Lactobacillus de 100 muestras de saliva. La cepa aislada más común fue L. gasseri (n = 18), seguida por L. vaginalis (n = 3) y L. salivarius (n = 3). Todas las cepas de Lactobacillus demostraron actividad antibacteriana contra al menos uno de los patógenos investigados. Sin embargo, los resultados más fuertes fueron obtenidos por L. vaginalis contra K. pneumonia. No se encontraron correlación entre la presencia de algunas de las treinta cepas de Lactobacillus y la promoción de la salud. Sin embargo, solo la especie L. gasseri tuvo un impacto positivo significativo en la salud de sus hospedadores (P

Aims: Diabetes mellitus is a metabolic disorder characterised by inadequate pancreatic insulin secretion or the insulin present being unable to perform its function properly. Consistent with the beneficial effects of probiotics and their ability to lower glucose levels, an impact on diabetes treatment is also expected. The aim of this study was to evaluate the effect of Lactobacillus casei on various either biochemical parameters in a diabetic mice model.Methods: In the present study, 24 mice were divided into diabetic and control groups. Further, each group was categorised into two subgroups. The diabetic and control subgroups were fed carrot juice or Lactobacillus casei in carrot juice. Diabetes was induced by streptozotocin (STZ). For 30 days, the mice were fed 2 ml carrot juice, and Lactobacillus casei in carrot juice (with lactobacillus 109 cfu/ml) by gavage. Then, blood samples were collected to assay biochemical parameters.Results: The results of this study showed that Lactobacillus casei (ATCC39392) significantly reduced blood glucose (BG) levels in diabetic mice receiving the probiotic, but did not cause a significant change in BG levels in control mice receiving the probiotic. When comparing insulin, insulin-like growth factor I (IGF-I) and C-peptide in the four groups, it was found that insulin and C-peptide were significantly different in all groups except for the control group treated with a mixture of probiotic Lactobacillus casei and carrot juice.Conclusion: Our results showed that probiotic Lactobacillus casei effectively reduces BG levels in diabetic mice treated with this bacterium.Keywords: diabetes, Lactobacillus casei, probiotic