s.farajnia farajnia - Academia.edu (original) (raw)

Papers by s.farajnia farajnia

Immunology Letters, Dec 1, 2016

EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, ... more EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. This tumor specific antigen has emerged as a promising candidate for antibody based therapy of several cancers. The aim of the present study was isolation and characterization of a human single chain antibody against EGFRvIII as a promising target for cancer therapy. For this, a synthetic peptide corresponding to EGFRvIII protein was used for screening the naive human scFv phage library. Selection was performed using a novel screening strategy for enrichment of rare specific clones. After five rounds of screening, six positive scFv clones against EGFRvIII were selected using monoclonal phage ELISA, among them, a clone with an amber mutation in VH CDR2 coding sequence showed higher reactivity. The mutation was corrected through site directed mutagenesis and then scFv fragment was expressed after subcloning into the bacterial expression vector. Expression in BL21 pLysS resulted in a highly soluble scFv appeared in soluble fraction of E. coli lysate. Bioinformatic in silico analysis between scFv and EGFRvIII sequences confirmed specific binding of desired scFv to EGFRvIII in CDR regions. The specific reactivity of the purified scFv with native EGFRvIII was confirmed by cell based ELISA and western blot. In conclusion, human anti- EGFRvIII scFv isolated from a scFv phage library displayed high reactivity with EGFRvIII. The scFv isolated in this study can be the groundwork for developing more effective diagnostic and therapeutic agents against EGFRvIII expressing cancers.

Biomedicine & Pharmacotherapy, Mar 1, 2018

Overexpression of renin angiotensin system (RAS) components and nuclear factor-kappa B (NF-kB) ha... more Overexpression of renin angiotensin system (RAS) components and nuclear factor-kappa B (NF-kB) has a key role in various cancers. Blockade of RAS and NF-kB pathway has been suggested to reduce cancer cell proliferation. This study aimed to investigate the role of angiotensin II and NF-kB pathway in liver hepatocellular carcinoma cell line (HepG2) proliferation by using azilsartan (as a novel Ag II antagonist) and Bay 11-7082 (as NF-kB inhibitor). HepG2 cells were treated with different concentrations of azilsartan and Bay 11-7082. Cytotoxicity was determined after 24, 48, and 72 h by MTT assay. Reactive oxygen spices (ROS) generation and cytochrome c release were measured following azilsartan and Bay11-7082 treatment. Apoptosis was analyzed qualitatively by DAPI staining and quantitatively through flow cytometry methodologies and Bax and Bcl-2 mRNA and protein levels were assessed by real time PCR and ELISA methods, respectively. The cytotoxic effects of different concentration of azilsartan and Bay11-7082 on HepG2 cells were observed as a reduction in cell viability, increased ROS formation, cytochrome c release and apoptosis induction. These effects were found to correlate with a shift in Bax level and a downward trend in the expression of Bcl-2. These findings suggest that azilsartan and Bay11-7082 in combination or alone have strong potential as an agent for prevention or treatment of liver cancer after further studies.

Iranian Journal of Medical Microbiology, 2015

Medical journal of Tabriz University of Medical Sciences and Health Services, Mar 22, 2009

Advanced Pharmaceutical Bulletin, Dec 22, 2016

Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I... more Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I + J (Tomlinson I+ J), HB2151and KM13 helper phage, 12 (The Medical Research Council (MRC), Cambridge, UK) and, E. coli TG1were used for isolation of specific antibody clones and production of scFvs. 12-14

BMC Infectious Diseases, Mar 24, 2021

Background: Pseudomonas aeruginosa is the leading cause of nosocomial infections, especially in p... more Background: Pseudomonas aeruginosa is the leading cause of nosocomial infections, especially in people with a compromised immune system. Targeting virulence factors by neutralizing antibodies is a novel paradigm for the treatment of antibiotic-resistant pseudomonas infections. In this respect, exotoxin A is one of the most potent virulence factors in P. aeruginosa. The present study was carried out to identify a novel human scFv antibody against the P. aeruginosa exotoxin A domain I (ExoA-DI) from a human scFv phage library. Methods: The recombinant ExoA-DI of P. aeruginosa was expressed in E. coli, purified by Ni-NTA column, and used for screening of human antibody phage library. A novel screening procedure was conducted to prevent the elimination of rare specific clones. The phage clone with high reactivity was evaluated by ELISA and western blot. Results: Based on the results of polyclonal phage ELISA, the fifth round of biopanning leads to the isolation of several ExoA-DI reactive clones. One positive clone with high affinity was selected by monoclonal phage ELISA and used for antibody expression. The purified scFv showed high reactivity with the recombinant domain I and fulllength native exotoxin A. Conclusions: The purified anti-exotoxin A scFv displayed high specificity against exotoxin A. The human scFv identified in this study could be the groundwork for developing a novel therapeutic agent to control P. aeruginosa infections.

Current Pharmaceutical Design, May 23, 2017

Iranian Journal of Biotechnology, Oct 1, 2011

Low molecular size additives such as L-arginine and the redox compounds have been used both in th... more Low molecular size additives such as L-arginine and the redox compounds have been used both in the culture medium and in vitro refolding to increase recombinant proteins production. Additives increase protein refolding and yield of active proteins by suppressing aggregate formation or enhancing refolding process. In this work, a comparative study was performed on refolding of recombinant plasminogen activator (rPA) in the presence of different concentrations of denaturants and additives. Escherichia coli-expressed rPA inclusion bodies were solubilized in chaotropic denaturants and subjected to protein refolding by dilution method. The effects of various additives, the impact of pH, residual Guanidin Hydrochloride (Gn-HCl) and Dithiothreitol (DTT) on refolding process were investigated. The refolding process was assessed by determination of protein solubility and biological assay. The results of the study demonstrated that the best condition for solubilizing the rPA inclusion body was 6M guanidine hydrochloride at pH=10. In refolding step, Larginine showed increasing effect on suppression of aggregation at concentrations of 200-1000 mM. Glutathione pairs (GSH-GssG) showed refolding enhancer effect in a range of 2-20 mM. The highest refolding yield was obtained in 500 mM L-arginine and reduced/oxidized glutathione 10:1 ratio in pH 10. In conclusion, the results show that L-arginine plays an important role in the refolding of human PA, preventing the aggregation of folding intermediate, and glutathione pair is essential for the correct refolding. The results also revealed that higher solubility in the presence of higher concentration of L-arginine (> 500 mM) or pH (>10) is not associated with higher activity.

Biologicals, Nov 1, 2016

Phage display is a prominent screening technique for development of novel high affinity antibodie... more Phage display is a prominent screening technique for development of novel high affinity antibodies against almost any antigen. However, removing false positive clones in screening process remains a challenge. The aim of this study was to develop an efficient and rapid method for isolation of high affinity scFvs by removing NSBs without losing rare specific clones. Therefore, a novel two rounds strategy called invert biopanning was developed for isolating high affinity scFvs against EGFRvIII antigen from human scFv library. The efficiency of invert biopanning method (procedure III) was analyzed by comparing with results of conventional biopanning methods (procedures I and II). According to the results of polyclonal ELISA, the second round of procedure III displayed highest binding affinity against EGFRvIII peptide accompanied by lowest NSB comparing to other two procedures. Several positive clones were identified among output phages of procedure III by monoclonal phage ELISA which displayed high affinity to EGFRvIII antigen. In conclusion, results of our study indicate that invert biopanning is an efficient method for avoiding NSBs and conservation of rare specific clones during screening of a scFv phage library. Novel anti EGFRvIII scFv isolated could be a promising candidate for potential use in treatment of EGFRvIII expressing cancers.

Background: Pseudomonas aeruginosa is known as the leading cause of nosocomial infections especia... more Background: Pseudomonas aeruginosa is known as the leading cause of nosocomial infections especially in people with a compromised immune system. Targeting virulence factors by neutralizing antibodies is a novel paradigm for the treatment of antibiotic-resistant pseudomonas infections.Methods: In this respect, exotoxin A is one of the most potent virulence factors in P. aeruginosa. The present study was conducted to identify a novel human scFv antibody against domain I of P. aeruginosa exotoxin A from a human scFv phage library. For this, the recombinant domain I of exotoxin A was expressed in E. coli and purified by Ni-NTA column. A novel screening procedure was conducted to prevent the elimination of rare specific clones. Based on polyclonal phage ELISA results, the fifth round of biopanning was selected to identify specific phage clones.Results: Two positive clones were found by monoclonal phage. The phage clone with high reactivity was evaluated by ELISA and western blot. The pur...

Progress in Biological Sciences, 2017

Production of Extended spectrum β-lactamases (ESBLs) is a common mechanism of resistance in multi... more Production of Extended spectrum β-lactamases (ESBLs) is a common mechanism of resistance in multidrug- Pseudomonas aeruginosa, but the frequency of different ESBLs may vary significantly in different parts of the world. The aim of this study was to investigate the prevalence of OXA-2/OXA-10 type ESBLs and class 1 integron among clinical isolates of P. aeruginosa in Tabriz, North West of Iran. A total of 110 P. aeruginosa isolates was entered in the study. Antibiotic susceptibility was determined by disk diffusion method. Production of ESBL was confirmed by combined disc method, and polymerase chain reaction was used for detection of OXA-2/OXA-10 beta-lactamases and class 1 integrons. Antibiotic susceptibility tests revealed that the highest resistance rate was against aztreonam (82%) and cefepime (77.3%), whereas the highest susceptibility was to imipenem (71%), meropenem (66.4%) and piperacillin/tazobactam (37.3%). In combined disc test, 68 isolates (61.8%) were ESBL producers. PCR...

Iranian Journal of Basic Medical Sciences, 2013

Objective(s): Drug resistant Acinetobacter baumannii have emerged as a major problem in many hosp... more Objective(s): Drug resistant Acinetobacter baumannii have emerged as a major problem in many hospitals and intensive care units. Various types of extended spectrum beta-lactamases (ESBLs) are responsible for resistance to beta-lactam antibiotics in different parts of the world. The objective of this study was to determine the prevalence of integron class1 (INT 1) and ESBL types PER-1, PER-2 and VEB-1 among A. baumannii strains isolated from Tabriz, North-West of Iran. Material and Methods: A total of 100 A. baumannii isolates collected from different clinical samples were included in the study. Antimicrobial susceptibility profiles were determined using the Kirby Bauer disk diffusion method. Production of ESBL was investigated by testing resistance against ceftazidime, cefotaxime, ceftriaxone and verified by Double Disk Synergy Test. DNA was extracted from the isolates and the frequency of INT 1 and ESBL types PER-1, PER-2 and VEB-1 were determined by PCR using specific primers. Res...

Applied Microbiology and Biotechnology, 2019

Escalating antibiotic resistance is now a serious menace to global public health. It may be led t... more Escalating antibiotic resistance is now a serious menace to global public health. It may be led to the emergence of "postantibiotic age" in which most of infections are untreatable. At present, there is an essential need to explore novel therapeutic strategies as a strong and sustainable pipeline to combat antibiotic-resistant infections. This review focuses on recent advances in this area including therapeutic antibodies, antimicrobial peptides, vaccines, gene therapy, genome editing, and phage therapy for tackling drug-resistant infections.

Iranian Journal of Biotechnology, 2018

Background Immunotoxins are cytotoxic proteins that were emerged as a modern strategy for the can... more Background Immunotoxins are cytotoxic proteins that were emerged as a modern strategy for the cancer treatment (1). These proteins consist of the two moieties, a targeting moiety, and a toxic portion. Antibodies are among the common targeting moieties used in immunotoxin (IT) preparations due to their specific bindings to the targets. Various toxic agents have been used in immunotoxins including chemical and biological toxins (1, 2). Bacterial exotoxins derived from Pseudomonas aeroginosa (P. aeruginosa; PE) and Corynebacterium (C.) diphteriae are the two most common toxins used

Jundishapur Journal of Microbiology, 2017

Background: Multidrug resistant (MDR) Acinetobacter baumanii strains have emerged as novel nosoco... more Background: Multidrug resistant (MDR) Acinetobacter baumanii strains have emerged as novel nosocomial pathogens threatening patients' lives, especially in intensive-care units (ICU). Various types of extended-spectrum β-lactamases (ESBLs) are involved in conferring resistance to β-lactam antibiotics, making their genotypic characterization an essential prerequisite to take proper preventative measures. Objectives: The aim of this study was to determine the antimicrobial susceptibility and prevalence of blaTEM, blaSHV, blaCTX-M, blaOXA-2, and blaOXA-10 genes among A. baumanii isolates obtained from patients in Tabriz city, Northwest Iran. Methods: The clinical isolates of A. baumanii were collected from patients hospitalized in the Imam Reza hospital of Tabriz. Antimicrobial susceptibility patterns were determined by the disk diffusion method. The frequency of different ESBLS resistance genes were determined by PCR. Results: Antimicrobial susceptibility testing through the disk diffusion method revealed that the lowest resistance rates were against polymyxin B (16%), colistin (23%), and rifampin (27%); whereas the highest resistance rate was observed against ticarcillin (100%), cefixime (100%), and ceftizoxim (100%). Screening by double disk synergy test showed that 60% of the isolates were ESBL producers. PCR technique on ESBL-positive isolates determined blaSHV gene as the most prevalent (31.6%) and blaOXA-10 as the least prevalent (8.3%) among the studied resistance genes. Conclusions: The high prevalence of resistance genes supported the essential role of ESBLs in antibiotic resistance of A. baumanii.

Advanced Pharmaceutical Bulletin, 2016

Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I... more Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I + J (Tomlinson I+ J), HB2151and KM13 helper phage, 12 (The Medical Research Council (MRC), Cambridge, UK) and, E. coli TG1were used for isolation of specific antibody clones and production of scFvs. 12-14

Journal of Drug Targeting, 2016

Phage display technology as a selection based system is an attractive method for evolution of new... more Phage display technology as a selection based system is an attractive method for evolution of new biological drugs. Unique ability of phage libraries for displaying proteins on bacteriophages surfaces enable them to make a major contribution in diverse fields of researches related to the diagnosis and therapy of diseases. One of the great challenges facing researchers is the modification of phage display technology and the development of new applications. This article reviews the molecular basis of phage display library, and summarizes the novel and specific applications of this technique in the field of biological drugs development including therapeutic antibodies, peptides, vaccines, and catalytic antibodies.

Microbial Drug Resistance, 2012

Immunology Letters, Dec 1, 2016

EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, ... more EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. This tumor specific antigen has emerged as a promising candidate for antibody based therapy of several cancers. The aim of the present study was isolation and characterization of a human single chain antibody against EGFRvIII as a promising target for cancer therapy. For this, a synthetic peptide corresponding to EGFRvIII protein was used for screening the naive human scFv phage library. Selection was performed using a novel screening strategy for enrichment of rare specific clones. After five rounds of screening, six positive scFv clones against EGFRvIII were selected using monoclonal phage ELISA, among them, a clone with an amber mutation in VH CDR2 coding sequence showed higher reactivity. The mutation was corrected through site directed mutagenesis and then scFv fragment was expressed after subcloning into the bacterial expression vector. Expression in BL21 pLysS resulted in a highly soluble scFv appeared in soluble fraction of E. coli lysate. Bioinformatic in silico analysis between scFv and EGFRvIII sequences confirmed specific binding of desired scFv to EGFRvIII in CDR regions. The specific reactivity of the purified scFv with native EGFRvIII was confirmed by cell based ELISA and western blot. In conclusion, human anti- EGFRvIII scFv isolated from a scFv phage library displayed high reactivity with EGFRvIII. The scFv isolated in this study can be the groundwork for developing more effective diagnostic and therapeutic agents against EGFRvIII expressing cancers.

Biomedicine & Pharmacotherapy, Mar 1, 2018

Overexpression of renin angiotensin system (RAS) components and nuclear factor-kappa B (NF-kB) ha... more Overexpression of renin angiotensin system (RAS) components and nuclear factor-kappa B (NF-kB) has a key role in various cancers. Blockade of RAS and NF-kB pathway has been suggested to reduce cancer cell proliferation. This study aimed to investigate the role of angiotensin II and NF-kB pathway in liver hepatocellular carcinoma cell line (HepG2) proliferation by using azilsartan (as a novel Ag II antagonist) and Bay 11-7082 (as NF-kB inhibitor). HepG2 cells were treated with different concentrations of azilsartan and Bay 11-7082. Cytotoxicity was determined after 24, 48, and 72 h by MTT assay. Reactive oxygen spices (ROS) generation and cytochrome c release were measured following azilsartan and Bay11-7082 treatment. Apoptosis was analyzed qualitatively by DAPI staining and quantitatively through flow cytometry methodologies and Bax and Bcl-2 mRNA and protein levels were assessed by real time PCR and ELISA methods, respectively. The cytotoxic effects of different concentration of azilsartan and Bay11-7082 on HepG2 cells were observed as a reduction in cell viability, increased ROS formation, cytochrome c release and apoptosis induction. These effects were found to correlate with a shift in Bax level and a downward trend in the expression of Bcl-2. These findings suggest that azilsartan and Bay11-7082 in combination or alone have strong potential as an agent for prevention or treatment of liver cancer after further studies.

Iranian Journal of Medical Microbiology, 2015

Medical journal of Tabriz University of Medical Sciences and Health Services, Mar 22, 2009

Advanced Pharmaceutical Bulletin, Dec 22, 2016

Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I... more Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I + J (Tomlinson I+ J), HB2151and KM13 helper phage, 12 (The Medical Research Council (MRC), Cambridge, UK) and, E. coli TG1were used for isolation of specific antibody clones and production of scFvs. 12-14

BMC Infectious Diseases, Mar 24, 2021

Background: Pseudomonas aeruginosa is the leading cause of nosocomial infections, especially in p... more Background: Pseudomonas aeruginosa is the leading cause of nosocomial infections, especially in people with a compromised immune system. Targeting virulence factors by neutralizing antibodies is a novel paradigm for the treatment of antibiotic-resistant pseudomonas infections. In this respect, exotoxin A is one of the most potent virulence factors in P. aeruginosa. The present study was carried out to identify a novel human scFv antibody against the P. aeruginosa exotoxin A domain I (ExoA-DI) from a human scFv phage library. Methods: The recombinant ExoA-DI of P. aeruginosa was expressed in E. coli, purified by Ni-NTA column, and used for screening of human antibody phage library. A novel screening procedure was conducted to prevent the elimination of rare specific clones. The phage clone with high reactivity was evaluated by ELISA and western blot. Results: Based on the results of polyclonal phage ELISA, the fifth round of biopanning leads to the isolation of several ExoA-DI reactive clones. One positive clone with high affinity was selected by monoclonal phage ELISA and used for antibody expression. The purified scFv showed high reactivity with the recombinant domain I and fulllength native exotoxin A. Conclusions: The purified anti-exotoxin A scFv displayed high specificity against exotoxin A. The human scFv identified in this study could be the groundwork for developing a novel therapeutic agent to control P. aeruginosa infections.

Current Pharmaceutical Design, May 23, 2017

Iranian Journal of Biotechnology, Oct 1, 2011

Low molecular size additives such as L-arginine and the redox compounds have been used both in th... more Low molecular size additives such as L-arginine and the redox compounds have been used both in the culture medium and in vitro refolding to increase recombinant proteins production. Additives increase protein refolding and yield of active proteins by suppressing aggregate formation or enhancing refolding process. In this work, a comparative study was performed on refolding of recombinant plasminogen activator (rPA) in the presence of different concentrations of denaturants and additives. Escherichia coli-expressed rPA inclusion bodies were solubilized in chaotropic denaturants and subjected to protein refolding by dilution method. The effects of various additives, the impact of pH, residual Guanidin Hydrochloride (Gn-HCl) and Dithiothreitol (DTT) on refolding process were investigated. The refolding process was assessed by determination of protein solubility and biological assay. The results of the study demonstrated that the best condition for solubilizing the rPA inclusion body was 6M guanidine hydrochloride at pH=10. In refolding step, Larginine showed increasing effect on suppression of aggregation at concentrations of 200-1000 mM. Glutathione pairs (GSH-GssG) showed refolding enhancer effect in a range of 2-20 mM. The highest refolding yield was obtained in 500 mM L-arginine and reduced/oxidized glutathione 10:1 ratio in pH 10. In conclusion, the results show that L-arginine plays an important role in the refolding of human PA, preventing the aggregation of folding intermediate, and glutathione pair is essential for the correct refolding. The results also revealed that higher solubility in the presence of higher concentration of L-arginine (> 500 mM) or pH (>10) is not associated with higher activity.

Biologicals, Nov 1, 2016

Phage display is a prominent screening technique for development of novel high affinity antibodie... more Phage display is a prominent screening technique for development of novel high affinity antibodies against almost any antigen. However, removing false positive clones in screening process remains a challenge. The aim of this study was to develop an efficient and rapid method for isolation of high affinity scFvs by removing NSBs without losing rare specific clones. Therefore, a novel two rounds strategy called invert biopanning was developed for isolating high affinity scFvs against EGFRvIII antigen from human scFv library. The efficiency of invert biopanning method (procedure III) was analyzed by comparing with results of conventional biopanning methods (procedures I and II). According to the results of polyclonal ELISA, the second round of procedure III displayed highest binding affinity against EGFRvIII peptide accompanied by lowest NSB comparing to other two procedures. Several positive clones were identified among output phages of procedure III by monoclonal phage ELISA which displayed high affinity to EGFRvIII antigen. In conclusion, results of our study indicate that invert biopanning is an efficient method for avoiding NSBs and conservation of rare specific clones during screening of a scFv phage library. Novel anti EGFRvIII scFv isolated could be a promising candidate for potential use in treatment of EGFRvIII expressing cancers.

Background: Pseudomonas aeruginosa is known as the leading cause of nosocomial infections especia... more Background: Pseudomonas aeruginosa is known as the leading cause of nosocomial infections especially in people with a compromised immune system. Targeting virulence factors by neutralizing antibodies is a novel paradigm for the treatment of antibiotic-resistant pseudomonas infections.Methods: In this respect, exotoxin A is one of the most potent virulence factors in P. aeruginosa. The present study was conducted to identify a novel human scFv antibody against domain I of P. aeruginosa exotoxin A from a human scFv phage library. For this, the recombinant domain I of exotoxin A was expressed in E. coli and purified by Ni-NTA column. A novel screening procedure was conducted to prevent the elimination of rare specific clones. Based on polyclonal phage ELISA results, the fifth round of biopanning was selected to identify specific phage clones.Results: Two positive clones were found by monoclonal phage. The phage clone with high reactivity was evaluated by ELISA and western blot. The pur...

Progress in Biological Sciences, 2017

Production of Extended spectrum β-lactamases (ESBLs) is a common mechanism of resistance in multi... more Production of Extended spectrum β-lactamases (ESBLs) is a common mechanism of resistance in multidrug- Pseudomonas aeruginosa, but the frequency of different ESBLs may vary significantly in different parts of the world. The aim of this study was to investigate the prevalence of OXA-2/OXA-10 type ESBLs and class 1 integron among clinical isolates of P. aeruginosa in Tabriz, North West of Iran. A total of 110 P. aeruginosa isolates was entered in the study. Antibiotic susceptibility was determined by disk diffusion method. Production of ESBL was confirmed by combined disc method, and polymerase chain reaction was used for detection of OXA-2/OXA-10 beta-lactamases and class 1 integrons. Antibiotic susceptibility tests revealed that the highest resistance rate was against aztreonam (82%) and cefepime (77.3%), whereas the highest susceptibility was to imipenem (71%), meropenem (66.4%) and piperacillin/tazobactam (37.3%). In combined disc test, 68 isolates (61.8%) were ESBL producers. PCR...

Iranian Journal of Basic Medical Sciences, 2013

Objective(s): Drug resistant Acinetobacter baumannii have emerged as a major problem in many hosp... more Objective(s): Drug resistant Acinetobacter baumannii have emerged as a major problem in many hospitals and intensive care units. Various types of extended spectrum beta-lactamases (ESBLs) are responsible for resistance to beta-lactam antibiotics in different parts of the world. The objective of this study was to determine the prevalence of integron class1 (INT 1) and ESBL types PER-1, PER-2 and VEB-1 among A. baumannii strains isolated from Tabriz, North-West of Iran. Material and Methods: A total of 100 A. baumannii isolates collected from different clinical samples were included in the study. Antimicrobial susceptibility profiles were determined using the Kirby Bauer disk diffusion method. Production of ESBL was investigated by testing resistance against ceftazidime, cefotaxime, ceftriaxone and verified by Double Disk Synergy Test. DNA was extracted from the isolates and the frequency of INT 1 and ESBL types PER-1, PER-2 and VEB-1 were determined by PCR using specific primers. Res...

Applied Microbiology and Biotechnology, 2019

Escalating antibiotic resistance is now a serious menace to global public health. It may be led t... more Escalating antibiotic resistance is now a serious menace to global public health. It may be led to the emergence of "postantibiotic age" in which most of infections are untreatable. At present, there is an essential need to explore novel therapeutic strategies as a strong and sustainable pipeline to combat antibiotic-resistant infections. This review focuses on recent advances in this area including therapeutic antibodies, antimicrobial peptides, vaccines, gene therapy, genome editing, and phage therapy for tackling drug-resistant infections.

Iranian Journal of Biotechnology, 2018

Background Immunotoxins are cytotoxic proteins that were emerged as a modern strategy for the can... more Background Immunotoxins are cytotoxic proteins that were emerged as a modern strategy for the cancer treatment (1). These proteins consist of the two moieties, a targeting moiety, and a toxic portion. Antibodies are among the common targeting moieties used in immunotoxin (IT) preparations due to their specific bindings to the targets. Various toxic agents have been used in immunotoxins including chemical and biological toxins (1, 2). Bacterial exotoxins derived from Pseudomonas aeroginosa (P. aeruginosa; PE) and Corynebacterium (C.) diphteriae are the two most common toxins used

Jundishapur Journal of Microbiology, 2017

Background: Multidrug resistant (MDR) Acinetobacter baumanii strains have emerged as novel nosoco... more Background: Multidrug resistant (MDR) Acinetobacter baumanii strains have emerged as novel nosocomial pathogens threatening patients' lives, especially in intensive-care units (ICU). Various types of extended-spectrum β-lactamases (ESBLs) are involved in conferring resistance to β-lactam antibiotics, making their genotypic characterization an essential prerequisite to take proper preventative measures. Objectives: The aim of this study was to determine the antimicrobial susceptibility and prevalence of blaTEM, blaSHV, blaCTX-M, blaOXA-2, and blaOXA-10 genes among A. baumanii isolates obtained from patients in Tabriz city, Northwest Iran. Methods: The clinical isolates of A. baumanii were collected from patients hospitalized in the Imam Reza hospital of Tabriz. Antimicrobial susceptibility patterns were determined by the disk diffusion method. The frequency of different ESBLS resistance genes were determined by PCR. Results: Antimicrobial susceptibility testing through the disk diffusion method revealed that the lowest resistance rates were against polymyxin B (16%), colistin (23%), and rifampin (27%); whereas the highest resistance rate was observed against ticarcillin (100%), cefixime (100%), and ceftizoxim (100%). Screening by double disk synergy test showed that 60% of the isolates were ESBL producers. PCR technique on ESBL-positive isolates determined blaSHV gene as the most prevalent (31.6%) and blaOXA-10 as the least prevalent (8.3%) among the studied resistance genes. Conclusions: The high prevalence of resistance genes supported the essential role of ESBLs in antibiotic resistance of A. baumanii.

Advanced Pharmaceutical Bulletin, 2016

Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I... more Materials and Methods ScFv-Phage Library, Bacteria, and Reagents The Human scFv phage libraries I + J (Tomlinson I+ J), HB2151and KM13 helper phage, 12 (The Medical Research Council (MRC), Cambridge, UK) and, E. coli TG1were used for isolation of specific antibody clones and production of scFvs. 12-14

Journal of Drug Targeting, 2016

Phage display technology as a selection based system is an attractive method for evolution of new... more Phage display technology as a selection based system is an attractive method for evolution of new biological drugs. Unique ability of phage libraries for displaying proteins on bacteriophages surfaces enable them to make a major contribution in diverse fields of researches related to the diagnosis and therapy of diseases. One of the great challenges facing researchers is the modification of phage display technology and the development of new applications. This article reviews the molecular basis of phage display library, and summarizes the novel and specific applications of this technique in the field of biological drugs development including therapeutic antibodies, peptides, vaccines, and catalytic antibodies.

Microbial Drug Resistance, 2012