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Fatemeh Hemmati,1,2 Roya Salehi,3 Reza Ghotaslou,4 Hossein Samadi Kafil,3,4 Alka Hasani,4 Pourya Gholizadeh,1,2 Roghayeh Nouri,1,2 Mohammad Ahangarzadeh Rezaee1,4 1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 3Drug Applied Research Center, Tabriz University of Medical Science, Tabriz, Iran; 4Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranCorrespondence: Mohammad Ahangarzadeh RezaeeImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranTel + 98-4133364661Email rezaee.mohammad@gmail.comAbstract: There has been excessive rate of use of antibiotics to fight Pseudomonas aeruginosa (P. aeruginosa) infections worldwide, which has consequently caused the increased resistance to multiple antibiotics in this pathogen. Due to the widespread resistance and the current poor effect of antibiotics consumed to treat P. aeruginosa infections, finding some novel alternative therapeutic methods are necessary for the treatment of infections. The P. aeruginosa biofilms can cause severe infections leading to the increased antibiotic resistance and mortality rate among the patients. In this regard, there are no approaches that can efficiently manage these infections; therefore, novel and effective antimicrobial and antibiofilm agents are needed to control and treat these bacterial infections. Quorum sensing inhibitors (QSIs) or quorum quenchings (QQs) are now considered as potential therapeutic alternatives and/or adjuvants to the current failing antibiotics, which can control the virulence traits of the pathogens, so as a result, the host immune system can quickly eliminate bacteria. Thus, the aims of this review article were presenting a brief explanation of the research reports on the natural and synthetic QSIs of P. aeruginosa, and the assessment of the current understanding on the QS mechanisms and various QQ strategies in P. aeruginosa.Keywords: Pseudomonas aeruginosa, quorum quenchings, quorum sensing, nanoparticle, natural compounds, synthetic compounds

Alka Hasani,1– 3 Elghar Soltani,1,2 Mohammad Ahangarzadeh Rezaee,1,2 Tahereh Pirzadeh,2 Mahin Ahangar Oskouee,2 Akbar Hasani,4 Pourya Gholizadeh,2 Arezoo Noie Oskouie,2 Ehsan Binesh5 1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical, Sciences, Tabriz, Iran; 3Sina Hospital, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; 4Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 5Department of Infectious Disease, School of Medicine, Shahroud University of Medical Science, Shahroud, IranCorrespondence: Elghar SoltaniImmunology Research Center and Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranTel +989366295410Fax +984133808693Email elghar_soltani@yahoo.comObjective: Klebsiella pneumoniae, one of the clinical superbugs, causes diverse infections because of its variable capsular antigens. This study focused on K. pneumoniae and aimed to assess any correlation between capsular serotype, capsule-associated virulence genes, and evaluate its resistance to conventional antibiotics in order to gain insight into any regional differences.Materials and Methods: A total of 61 K. pneumoniae collected from various clinical specimens were confirmed genotypically. Clinical and demographic data for all patients were reviewed. All isolates were subjected to antimicrobial susceptibility tests. Capsular serotyping and capsule-associated virulence genes were studied using the molecular method.Results: All typeable isolates were typed into K5, K20, and K54 serotypes, and among them, K54 was observed to be predominant. The most common capsule-associated virulence genes comprised uge (93.4%), ycfM (91.8%), and wabG (88.5%), while wcaG (29.5%) and rmpA (21.3%) were noted at much lower prevalence rates. The gene wcaG was significantly associated with K54 positive isolates (p = 0.001), while rmpA was associated with K20 positive isolates (p = 0.01).Conclusion: Serotype K54 had a high frequency in isolates collected from patients with pulmonary diseases, while serotype K20 was associated with burn patients. Carbapenems and levofloxacin were the best therapeutic options for the treatment of infections with serotypes K20 and K54.Keywords: Klebsiella pneumoniae, capsular serotype, virulence factor, extended-spectrum beta-lactamase, multidrug-resistance, multiplex-PCR

Naser Alizadeh,1,2 Mohammad Ahangarzadeh Rezaee,1,3 Hossein Samadi Kafil,3 Alka Hasani,3 Mohammad Hossein Soroush Barhaghi,3 Morteza Milani,4 Fatemeh Yeganeh Sefidan,3 Mohammad Yousef Memar,3,5 Aidin Lalehzadeh,3 Reza Ghotaslou1,3 1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 3Department of Bacteriology and Virology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IR, Iran; 4Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Medical, University of Tabriz, Tabriz, Iran; 5Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, IranCorrespondence: Reza GhotaslouImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranTel/Fax + 984133364661Email rzgottaslo@yahoo.comBackground: Carbapenem-resistant Enterobacteriaceae (CRE) is a major concern leading to morbidity and mortality in the world. CRE often is becoming a cause of therapeutic failure in both hospital and community-acquired infections.Aim: This study aimed to investigate the resistance mechanisms of CRE by phenotypic and molecular methods.Materials and Methods: Sixty CRE (50 Klebsiella pneumoniae, 6 Escherichia coli, and 4 Enterobacter spp.) were isolated from October 2018 to June 2019. Antimicrobial susceptibility testing was carried out using phenotypic methods. The carbapenem resistance mechanisms including efflux pump hyperexpression, AmpC overproduction, carbapenemase genes, and deficiency in OmpK35 and OmpK36 were determined by phenotypic and molecular methods, respectively.Results: Sixty CRE (50 Klebsiella pneumoniae, 6 Escherichia coli, and 4 Enterobacter spp.) were isolated from October 2018 to June 2019. Amikacin was found to be the most effective drug against CRE isolates. All isolates were resistant to imipenem and meropenem by the micro-broth dilution. AmpC overproduction was observed in all Enterobacter spp. and three K. pneumoniae isolates. No efflux pump activity was found. Carba NP test and Modified Hodge Test could find carbapenemase in 59 (98%) isolates and 57 (95%) isolates, respectively. The most common carbapenemase gene was blaOXA-48-like (72.8%) followed by blaNDM (50.8%), blaIMP (18.6%), blaVIM (11.8%), and blaKPC (6.7%). The ompK35 and ompK36 genes were not detected in 10 and 7 K. pneumoniae isolates, respectively.Conclusion: The amikacin is considered as a very efficient antibiotic for the treatment of CRE isolates in our region. Carbapenemase production and overproduction of AmpC are the main carbapenem resistance mechanisms in CRE isolates. Finally, Carba NP test is a rapid and reliable test for early detection of carbapenemase-producing isolates.Keywords: amikacin, carbapenemase genes, carbapenem-resistant Enterobacteriaceae, Carba NP test

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, İzmir, 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

Purpose: Many antimicrobial medications are available to combat infections. However, the indiscriminate use of antibiotics has produced antibiotic resistance in the case of many bacterial pathogens. This study focuses on the development of nanoparticles (NPs) that enhance the in vitro antibiotic activity of vancomycin against multi-drug resistant (MDR) organisms. Methods: Spherical shaped thioglycolic acid-stabilized silver nanoparticles (TGA-AgNPs) were prepared by using a simple chemical reduction method. Then, vancomycin was conjugated to the terminal carboxyl of TGA in the presence of N-Hydroxysuccinimide (NHS) and N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC). Afterwards, the antibacterial activity of these nanoconjugates was examined by using the minimum inhibitory concentration (MIC) assay against MDR bacteria. Results: The rate of vancomycin bound to the AgNPs was 19.6%. The MIC values of vancomycin (Van)-capped AgNPs against tested pathogens were in the range of (3.2, 1.6, 0.8, 0.4, 0.2, 0.1, 0.05, and 0.025 µl/ml). The MIC was 0.1 µg/ml for VRE, MIC≤0.02 µg/ml for MRSE, and 0.05 µg/ml for S. aureus. The MIC corresponded to the MBC for all bacterial species. Conclusion: This study indicated that some antimicrobial agents like vancomycin can be conjugated with AgNPs. This can lead to increased antimicrobial activity against MDR microorganisms.