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Background: One of the primary and major aims in organ transplantation is to effectively prevent or treat infections. In the previous two decades, significant advancements have been made in the management of infection after transplantation; however, transplant recipients are at high risk of infectious complications. Objective: To evaluate the prevalence of bacterial infections and frequency of antimicrobial resistance in kidney transplant recipients. Methods: This retrospective study conducted on 356 patients receiving kidney in transplant hospital of Montaserieh, Mashhad, regardless of the underlying cause for a period of 24 months from March 20, 2013 to March 20, 2015. We studied cultures relevant to the samples sent to the microbiology laboratory. Results: Of 356 kidney recipients (206 men and 150 women), 115 (32.3%) received their transplants from a living donor; 241 (67.7%) received their transplants from a brain-dead patient. Of the total 365 patients, 112 (31.5%) had positive blood cultures at various time intervals after transplantation. The most common Gram-negative and Gram-positive organisms causing infection were respectively, Escherichia coli, and coagulase negative Staphylococcus with a prevalence of 66.1%, and 48.6%. The highest and lowest antibiotic resistance among Gram-positive isolates was nalidixic acid (100%), and nitrofurantoin (41.5%), respectively; The antibiotics for Gram-negative bacteria was amoxicillin (93.2%), and meropenem (14.7%), respectively. Conclusion: Due to the a high prevalence of infection in transplant recipients, appropriate antibiotic should be found before prescribing the drug; this would prevent introduction of new resistant strains as well as proving an effective use of the drug. [ABSTRACT FROM AUTHOR]

Background: The emergence of coronavirus disease in 2019 (COVID-19) appears to be having an impact on antibiotic resistance patterns. Specific circumstances during the COVID-19 era may have played a role in the spread of antimicrobial resistance (AMR). This study aimed to look at the changes in AMR patterns of Pseudomonas aeruginosa , Klebsiella pneumoniae , and Acinetobacter baumannii at Al-Zahra Hospital., Materials and Methods: From March 2021 to January 2023, 3651 clinical samples were collected from patients hospitalized at Isfahan's Al-Zahra Hospital. The Clinical and Laboratory Standards Institute recommended procedures for detecting gram-negative bacteria and assessing antibiotic susceptibility were used. We divided the information into three years., Results: Highest resistance rates were seen in A. baumannii to Ciprofloxacin (98.0%) and Ampicillin-Sulbactam (97.0%). For P. aeruginosa the resistance rate for Ceftazidime (36.1), Levofloxacin (37.8), and Meropenem (47.1) dropped seriously in 2022., Conclusion: During the second year of the pandemic in central Iran, all three species studied showed rising rates of AMR. This can be attributable to two peaks within Iran on May 6, 2021 and August 27, 2021. The results of this study show that P. aeruginosa , K. pneumoniae , and A. baumannii bacteria in central Iran have a higher level of antibiotic resistance than previously studied strains before the pandemic., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Advanced Biomedical Research.)

Thymol (Th) and d-limonene (L) exhibit low stability and are prone to oxidation when exposed to air, light, humidity, and high temperatures. This study examined the coencapsulation of Th and L into Ferula assafoetida gum (AFG) microparticles. Scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analyzer (TGA) were done to characterize the obtained complexes. Furthermore, the encapsulation efficiency, antibacterial properties, cytotoxicity, and anticancer properties of both the free and encapsulated forms of L and Th were measured. For all samples, by increasing the percentage of bioactive compound (L, Th, and L-Th) from 2.5 to 5 % w/w, the EE was increased. FTIR and XRD analysis results demonstrated that Th and L were successfully incorporated into the AFG. Additionally, thermogravimetric analysis showed that in the thermal graphs of all samples, the first weight loss occurred between 30 °C and 160 °C, which was due to the evaporation of water. In the free L and Th graph, a sharp reduction peak was observed in which 80 % of compounds were lost. These reduction peaks disappeared in the thermal graphs of L: AFG and Th: AFG revealing that the thermal stability of Th and L was significantly increased upon their incorporation into the AFG. The inclusion of Th into the AFG also led to an increase in its antibacterial activity, while L exhibited acceptable antibacterial activity, albeit not as high as Th. Additionally, according to the MIC results, Th: AFG had the best antibacterial activity among all compounds, especially on gram-positive bacteria. According to the result of the MTT assay, there was a significant difference between the IC 50 of free Th (123.4 μg/ml) and Th: AFG (2312 μg/ml), and free L (1762 μg/ml) and L: AFG (2480 μg/ml) showing that encapsulated Th and L into the AFG has decreased the cytotoxicity of free compounds against L929 cell line. Also, Th: AFG had the best anticancer activity against Hella and CT26 cell lines among all compounds. Finally, the flow cytometry analysis demonstrated that the encapsulated particles effectively eliminated cancer cells. The outcomes imply that AFG can be employed as a suitable delivery system to enhance the use of Th and L into the food and pharmaceutical industries., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare. Grant ID: 3400946. Funder: Isfahan University of Medical Sciences, Isfahan, Iran., (Copyright © 2024. Published by Elsevier B.V.)

The immune system is tightly regulated to prevent immune reactions to self-antigens and to avoid excessive immune responses during and after challenges from non-self-antigens. Inhibitory immune checkpoints (IICPs), as the major regulators of immune system responses, are extremely important for maintaining the homeostasis of cells and tissues. However, the high and sustained co-expression of IICPs in chronic infections, under persistent antigenic stimulations, results in reduced immune cell functioning and more severe and prolonged disease complications. Furthermore, IICPs-mediated interactions can be hijacked by pathogens in order to evade immune induction or effector mechanisms. Therefore, IICPs can be potential targets for the prognosis and treatment of chronic infectious diseases. This is especially the case with regards to the most challenging infectious disease of recent times, coronavirus disease-2019 (COVID-19), whose long-term complications can persist long after recovery. This article reviews the current knowledge about the kinetics and functioning of the IICPs during and post-COVID-19., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Relebactam, previously known as MK-7655, is currently being tested in combination with imipenem as a class A and class C β-lactamase inhibitor, including KPC from Klebsiella pneumoniae ., Objective: The objective of the current study was to evaluate the activity of imipenem/relebactam against gram-negative bacilli., Methods: After applying exclusion and inclusion criteria, 72 articles with full texts that describe the prevalence of imipenem/relebactam resistance were chosen for the meta-analysis and systematic review. Articles published between January 2015 and February 2023 were surveyed. The systematic literature search was conducted in PubMed, Web of Science, Google Scholar, and Scopus., Results: The pooled estimation of 282,621 sample isolates revealed that the prevalence rate of imipenem/relebactam resistance is roughly 14.6% (95% CI, 0.116%-0.182%)., Conclusions: The findings of this analysis show that imipenem/relebactam resistance is rare in the majority of developed countries. Given that relebactam has proven to restore the activity of imipenem against current clinical isolates, further research into imipenem/relebactam is necessary., Competing Interests: The authors have indicated that they have no conflicts of interest regarding the content of this article., (© 2023 The Author(s).)

Acinetobacter baumannii, as a nosocomial pathogen has become a worldwide concern in recent years. In the current study, the resistance to tetracyclines and colistin were assessed in the isolates from different provinces of Iran.During the timeline of this study, a number of 270 isolates of A. baumannii were collected from tracheal aspirates, wounds, urine and blood cultures. The minimum inhibitory concentration (MIC) for tetracycline, doxycycline, minocycline, tigecycline and colistin were evaluated. Tetracycline resistance genes were assessed by PCR. The mean expression level of adeB, adeJ and adeG were assessed using semi quantitative Real-Time PCR. The clonal relationship of the isolates was evaluated by the repetitive extragenic palindromic PCR (REP-PCR), International Clonal (IC) Lineage Multiplex PCR and multilocus sequence typing (MLST) (Pasteur scheme) methods.The MIC by microdilution method showed that 87.5, 51.4, 28, 0.74 and 0% of the isolates were resistant to tetracycline, doxycycline, minocycline, tigecycline and colistin respectively. The prevalence of tetracycline resistance genes was 99.2, 99.2, 98, 86.7, 10, 3.33, 0.37, 0% for adeB, adeJ, adeG, tetB, tetA(39), tetA, tetM and tetH in tetracycline-resistant isolates. Moreover, the expression level of adeB, adeJ, adeG genes in tigecycline-nonsusceptible A. baumannii (TNAB) strain was higher compared to the tigecycline-susceptible A. baumannii (TSAB). A broad genomic diversity was revealed, but ST2 was the most prevalent ST. Our results indicated that tetracycline resistance in Iran is mediated by resistance-nodulation-cell division (RND) and tetB efflux pumps.

Multidrug resistance of pathogenic microorganisms is a common problem in the treatment of infections. Therefore, searching for new agents with antimicrobial activities appears to be essential. Thrombocidin-1 (TC-1) is an antimicrobial peptide (AMP) derived from platelets. The present study aimed to produce recombinant TC-1 (rTC-1) with His tag to evaluate its antimicrobial activity and also predict its thermal-stability through molecular dynamic (MD) simulations. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration of rTC-1 against bacterial isolates were determined. Considering the importance of thermal-stability of proteins in their therapeutic applications, thermal-stability of rTC-1 predicted through MD simulation during 25ns at two important temperatures including avian normal body temperature and water boiling temperature at sea level. MIC results revealed that rTC1 had the most and least potency against Salmonella enteritidis and Escherichia coli , respectively. The root-mean-square deviation of rTC-1 during 25ns MD simulations revealed that this protein is stable at avian normal body temperature (40°C) but might lose stability at water boiling temperature at sea level. rTC-1 as an AMP has a good potency against some bacterial pathogens especially Salmonella spp. and E. coli 0157:H7. rTC-1 can be used as an alternative for common antimicrobial agents used in clinical settings.

Tuberculosis has been a major health problem worldwide for years; therefore, it is important to develop and produce an effective vaccine against this disease. In this study, the immunogenicity of Mycobacterium tuberculosis fusion protein (FP) encapsulated in liposomes containing DDA/TDB was evaluated. The FP was expressed in E. coli BL21 and encapsulated in liposomal formulations. Three weeks after the last subcutaneous immunization, IFN-γ, IL-4, IL-17, and IL-12 in spleen cell culture supernatants, and IgG2a, IgG1, and IgG2b titres in sera were measured. The greatest IFN-γ and IL-12 interleukin concentrations were observed in the DDA/TDB/CHOL liposomes containing the FP. Initial injection with BCG improved the efficacy of the DDA/TDB/CHOL/FP vaccine. The IgG2a/IgG1 ratio was also high in the DDA/TDB/CHOL/FP group; furthermore, the IgG2a/IgG1 ratio was increased in the BCG-primed, DDA/TDB/CHOL/FP-boosted group, indicating induction of a cellular immune response. Our study showed that the FP-containing DDA/TDB/CHOL liposomes induced a Th1 response. However, the groups that first received BCG and then DDA/TDB/CHOL/FP had the greatest Th1 response in terms of IFN-γ and IL-12 production of all the groups. This suggests that these formulations enhance the BCG vaccine's effectiveness.

Due to the emergence of multidrug-resistant bacteria, treatment options for infectious diseases are decreasing. Bacteriocins are small antimicrobial peptides produced by numerous bacteria that offer alternative therapeutic strategies to combat multidrug-resistant bacterial infections. We evaluated the cloning, functional expression, and antimicrobial activities of enterocin P (EntP), a class II bacteriocin member, in Chinese hamster ovary (CHO) cells. A synthetic gene matching CHO cell codon usage was designed from the known mature amino acid sequence of EntP and cloned into the protein expression vector pcDNA™3.1(+). CHO cells were transformed with the recombinant plasmid and cultured, and the recombinant protein was purified by affinity chromatography. Antimicrobial activities of the recombinant EntP were evaluated on Gram-positive, Gram-negative, and multidrug-resistant pathogens. Recombinant EntP inhibited growth of a variety of bacteria, including pathogenic species known to cause nosocomial infections, often with multidrug-resistant strains. In addition, recombinant EntP demonstrated broad antimicrobial activities in both high salt medium and human plasma and was stable at high temperatures. The broad antimicrobial activity and stability of EntP make it an attractive therapeutic candidate, particularly for treatment of multidrug-resistant bacterial infections.

Background: Due to the ineffectiveness of the BCG vaccine, especially in adult pulmonary tuberculosis (TB), and variable efficacies against childhood forms of TB, developing an effective TB vaccine is a major priority in controlling this disease. The aim of this study was to evaluate the immunogenicity of a DOTAP liposome formulation containing a fusion protein (FP) containing Mycobacterium tuberculosis HspX, PPE44, and EsxV., Methods: The FP was expressed in E. coli BL21 cells and confirmed by SDS-PAGE and Western blots. The FP was then encapsulated in various liposomal formulations. Afterwards, liposomal size, zeta potential, and encapsulation efficiency were evaluated. Mice were subcutaneously vaccinated on days 0, 14, and 28 with liposomes containing the FP. Two weeks after the last injection, IFN-γ, IL-4, IL-17, and IL-12 in spleen cell culture supernatants, and IgG2a, IgG1, and IgG2b titers in sera were measured., Results: The FP concentration was 1mg/ml. The encapsulation efficiency of the liposomes varied from 69% in Lip (DOTAP/TDB/CHOL/FP) to 80% in Lip (DOTAP/CHOL/FP). The greatest IFN-γ and IL-12 levels were observed in BCG-primed mice that were boosted with Lip (DOTAP/CHOL/FP). In addition, IL-17 production was significantly greater in all groups than controls except in those that received histidine buffer and FP. The IgG2a/IgG1 ratios were greater in the Lip (DOTAP/TDB/CHOL/FP), Lip (DOTAP/CHOL/FP), Lip (DOTAP/CHOL), and BCG-primed and Lip (DOTAP/CHOL/FP)-boosted groups than in the other groups, indicating a cellular immune response., Conclusion: The liposomes containing DOTAP combined with the fusion protein induced a Th1 response. The mice that first received BCG and then Lip (DOTAP/CHOL/FP), produced the most IFN-γ and IL-12, indicating a strong Th1 response.

Purpose: Acinetobacter baumannii-calcoaceticus complex (ABC) make a great burden on health-care systems due to hospital-acquired infections and antibacterial resistance. Aminoglycoside in combination with other antibacterials used as treatment options. However, ABC species overcome this class of antibacterials in different ways. This study provides a comprehensive report on the distribution of aminoglycoside modifying enzymes (AMEs) and 16S rRNA methylase in Acinetobacter baumannii and Acinetobacter nosocomialis isolated from various provinces in Iran., Methods: During six month of study, from eight referral centers in seven provinces across the country, Iran, 178 A. baumannii and 43 A. nosocomialis isolates were collected. The minimum inhibitory concentration of amikacin, gentamicin, netilmicin, kanamycin and tobramycin were measured by microbroth dilution method. AMEs and 16S rRNA methylase variants were sought by PCR., Results: High rates of resistance were seen in all centers. MIC 50 and MIC 90 for all A. baumannii and A. nosocomialis isolates from different centers were > 512 mg/L. The most frequent AME was ant(3″)-Ia (aadA1) in both of A. baumannii (74.1%) and A. nosocomialis (86%). armA was detected in A. baumannii and A. nosocomialis at the frequency of 41.6% and 67.4%, respectively. rmtA, B, C, D, aac(3)-Ia (aacC1) and aac(6')-Im were not detected, neither in A. baumannii nor A. nosocomialis. Moreover, aac(6')-Ih was only found in A. baumannii isolates. The distribution of some of the ARGs was limited to a definite center., Conclusion: The overall high-level carriage of ARGs in Acinetobacter species may limited usage of this class of antibacterials as a treatment option., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Over the past 2 decades, significant advances have been made in the management of infections after transplant; however, transplant recipients are still at high risk of infectious complications. This study aimed to evaluate the prevalence of bacterial infections and antimicrobial resistance patterns in kidney transplant recipients., Materials and Methods: This cross-sectional study included 356 patients who received kidney transplants, regardless of the underlying disease, from 2013 to 2015 at the Montaserieh Transplant Hospital (Mashhad, Iran). Clinical samples collected from patients were sent to the microbiology laboratory for culture processing. Typing of bacteria was conducted, and susceptibility testing was performed according to the Clinical and Laboratory Standards Institute guideline by use the of disk diffusion agar method. Data were then analyzed by SPSS software (SPSS: An IBM Company, IBM Corporation, Armonk, NY, USA) using chi-square test., Results: Among 356 kidney recipients (206 men and 150 women), 115 (32.3%) received transplants from living donors and 241 (67.7%) received transplants from deceased donors. Of 356 total patients, 112 patients (31.5%) had an infection at various times after transplant. The most common gram-negative and gram-positive isolated bacteria were Escherichia coli and coagulase-negative Staphylococcus, with prevalence rates of 66.1% and 48.6%. Most of the isolates were resistant against selected antibiotics., Conclusions: Because of the high prevalence of infection among transplant patients, infection prevention should receive more attention, and antibiotic susceptibility should be determined before treatment.

Mycobacterium bovis is a neglected zoonotic organism that epidemiological studies are of crucial importance in identifying its source, control it and prevent it from spreading. The aim of this study was to investigate the most common spoligotypes of Mycobacterium bovis circulating around the world and introduce the most and least strong determine powers of loci for VNTR. We have used different databases such as ISC, science direct, Embase (Elsevier), Web of Science, Scopus and Medline via PubMed. Searches were performed by key words including: Mycobacterium bovis, MIRU -VNTR, spoligotyping and discrimination power. Finally, thirty-one articles were selected after filtering out some titles, abstracts and full texts. Spoligotype SB0120 was the most common circulating type on several continents while SB0121 existed in Europe, Africa and America. SB0140 was also detected in Asia, Europe and America. QUB3232 and QUB11b were more appropriate loci among the loci with high discriminatory power. MIRU 10 and MIRU4 were among the loci with poor discriminatory power. Taking the published data into consideration, SB0120 and SB0121 are predominant spoligotypes of M. bovis circulating among animals around the world. Determining the most common spoligotype of M. bovis is the key to find source of infection, control and prevent the disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: While the most nontuberculous mycobacteria (NTMs) species are considered as opportunistic pathogens, some of them are related to several human infections. It is believed that environment is the main source for these infections. Distribution and scattering pattern of NTMs has not been well studied in Iran and a few studies about this subject have been done, so the aim of this study was to determine prevalence of NTMs in environmental samples from Iran., Materials and Methods: Data about prevalence of NTMs in environmental samples from Iran were obtained by searching databases. The studies presenting cross-sectional or cohort and the papers with sample size ≥30 were included. Then, the meta-analysis was performed using Comprehensive Meta-Analysis software and Cochran's Q and I 2 tests. The strategy search was based PRISMA protocol is available online (PRISMA, http://www.prisma-statement.org)., Results: The results of this meta-analysis showed that overall combined prevalence of NTMs in environmental samples from Iran was 38.3%. The frequency of NTM was higher in the north of Iran (73.2%). The most prevalent rapid-growing mycobacterium was Mycobacterium fortuitum (19.8%), and the most dominant slow-growing mycobacterium was Mycobacterium flavescens (16.8%)., Conclusion: In regard to increasing incidence of disease in immunocompromised patients and existence of different types of mycobacteria species in environmental samples, efforts should be focused on measures that will specifically remove NTMs from habitats where susceptible individuals are exposed.