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Adolescence is a critical life period during which significant neurodevelopmental changes occur within the central nervous system. Consistently, substance abuse in this stage has been found to induce persistent changes in brain responsiveness to future drug challenges. Nowadays, heavy episodic alcohol consumption during adolescence, also known as binge-drinking behavior, is a growing concern in modern societies. On the other hand, alcohol is well known to act as a gateway drug, that is, it promotes the individual's craving for consumption of other drugs of abuse. With this in mind, we aimed to assess whether adolescent ethanol exposure could alter the development of tolerance and dependence to morphine, as an available common opioid drug. Tail flick test was used to measure thermal nociceptive changes in adult male Wistar rats undergone ethanol/vehicle exposure during adolescence. Furthermore, morphine withdrawal syndrome was induced by naloxone injection, and behavioral signs were recorded for 20 min. It was found that adolescent ethanol intake facilitates morphine analgesic tolerance and decreases baseline latency; however, the severity of dependence is not significantly altered. Moreover, we found that 15 days of treatment with omega-3 fatty acids (O3) prevents the mentioned ethanol-induced changes suggesting a therapeutic potential for this compound. O3 supplementation, as an inexpensive and noninvasive method, may assist the clinicians to reverse the adverse effect of alcohol binge drinking on adolescents' brains and to reduce the vulnerability to drug exposure in adulthood. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

No report exists on the role of Mastoparan B (MP-B) as an RND efflux pump inhibitor in multi-drug resistant (MDR)Acinetobacter baumannii. Here, we performed a series of in-silico experiments to predict the inhibition of the AdeB efflux pump by MP-B as a drug target agent. For this reason, an MDR strain ofA. baumanniiwas subjected to MICs against 12 antibiotics as well as MP-B. Expression of the adeB gene in the presence and absence of sub-MIC of MP-B was studied by qRT-PCR. It was found that MP-B had potent antimicrobial activity (MIC=1 μg/ml) associated with a 20-fold decrease in theadeB gene expression at the sub-MIC level. The stereochemical analysis using several automated servers confirmed that the AdeB protein is an inner membrane of the RND tripartite complex system with helix-turn-helix conformation and a pore rich in Phe, Ala, and Lys residue. Furthermore, 20 ligands were generated from the initial docked poses to create the correct protein-peptide complexes using the BioLiP pipeline. The pose showed high Z=1.2, C=1.41, TM=0.99, and RMSD=4.4 scores was selected for docking purposes. The molecular docking via AutoDock/Vina revealed that MP-B form H-bound with Val 499, Phe 454, Thr 474, Ser 461, Gly 465, and Tyr 468 residues of the AdeB helix-5 and caused a shift in the dihedral angle (Φ/Ψ) by distances of 9.0 Å, 9.3 Å, and 9.6 Å, respectively. This shift in folding was detected by AlphaFold 2 and influenced the overall druggability of the protein. From the above results, we concluded that MP-B can be a good candidate for bacterial efflux pump inhibition.

No report exists on the role of Mastoparan B (MP-B) as an RND efflux pump inhibitor in multi-drug resistant (MDR) Acinetobacter baumannii. Here, we performed a series of in-silico experiments to predict the inhibition of the AdeB efflux pump by MP-B as a drug target agent. For this reason, an MDR strain of A. baumannii was subjected to minimum inhibitory concentration (MIC) against 12 antibiotics as well as MP-B. Expression of the a deB gene in the absence and presence of sub-MIC of MP-B was studied by qRT-PCR. It was found that MP-B had potent antimicrobial activity (MIC=1 µg/ml) associated with a 20-fold decrease in its expression at sub-MIC of MP-B. The stereochemical analysis using several automated servers confirmed that the AdeB is an inner membrane of the RND tripartite complex system with helix-turn-helix conformation and a pore rich in Phe, Ala, and Lys residue. The best model that showed high accuracy (Z=1.2, C=1.41, TM=0.99, and RMSD=4.4) was selected for docking purposes using the Site Map tool, and the correct protein-peptide complexes were simulated in the BioLiP platform. The molecular docking via AutoDock/Vina suggested that MP-B form H-bound with amino acid residues of the AdeB helix-5 and caused a shift in the dihedral angle by distances of 9.0 Å, 9.3 Å, and 9.6 Å, respectively. This shift was detected by the AlphaFold 2 tool and influenced the overall druggability of the protein. From the results, we concluded that, MP-B can be a good candidate for inhibition of bacterial efflux pump.

Background: Acinetobacter baumannii has emerged as a critical pathogen with high morbidity and mortality in long-term hospitalized patients who stay in intensive care units. Carbapenemases and integrons are two critical DNA elements that contribute to the emergence of multidrug-resistant (MDR) A. baumannii. Objectives: The current study aimed at characterization and molecular detection of class 1, 2, and 3 integrons among carbapenemase-producing A. baumannii strains recovered from a clinical setting in Tehran, Iran. Methods: A total of 65 non-replicated clinical strains were considered in this study. Class 1, 2, and 3 carbapenemase genes and clonal relatedness of the isolates were investigated by PCR assay. Results: The prevalence of carbapenemases was as follows: blaOXA23 (92.31%), blaVIM (69.23%), and blaNDM (1.54%). In addition, PCR sequencing confirmed the presence of gene cassette arrays consisting of aacA4-catB8-aadA1 (12/46, 26.09%), aadB-aadA1 (26.09%, 12/46), arr2-cm1A5 (30.43%, 14/46), and dfrA1-aadA1 (7.39%, 8/46) in class 1 integron and dfrA1-sat2 (52.94%, 9/17), and sat2-aadA1 (47.06%, 8/17) in class 2 integron. Sequence-based typing of both blaOXA-51-like and ampC revealed the following distribution of three different clone types among isolates: clonal complex (CC) 10 (46.15%, 30/65), CC2 (40%, 26/65), and CC3 (13.85%, 9/65). Statistical analysis showed that the presence of the intI1, blaOXA23, blaVIM, or blaNDM genes can significantly increase the acquiring MDR phenotypes in A. baumannii isolates. Conclusions: High prevalence of carbapenemase-producing A. baumannii harboring integrons is alarming public health. It seems that class 1 integron can be served as a predictive biomarker for the presence of MDR phenotypes in the clinical setting. However, integrons do not carry carbapenemases in these strains.

Carbapenem resistance in Enterobacterales is a major and persistent public health problem worldwide. In current research, we present data of 96 Enterobacterales species collected from a clinical hospital in Isfahan, Iran. The bacterial identification was performed by standard biochemical tests and API 20E methods. Agar disk diffusion assay was performed to determine the phenotypic antibiotic resistance of strains. Polymerase chain reaction (PCR) was carried out to detect carbapenemase genes. In this manuscript, multiple antimicrobial resistance phenotype such as multiple carbapenem resistance determinants were detected. The data would provide important information on distribution of carbapenemase genes of those pathogenic bacteria in Iran.

Background & Aims Clostridioides difficile (C. difficile) has been identified as the leading cause of antibiotic associated diarrhea (AAD). Co-carriage of an intact pathogenicity locus (PaLoc) with binary toxin genes in C. difficile strains seems to be linked with severe disease outcomes in the infected patients. Epidemiology of C. difficile infection (CDI) in hospital setting and knowledge about their genetic context help us to decrease the morbidity, mortality, and costs associated with Clostridioides difficile infection. In the present study was aimed to characterize genetic diversity of PaLoc among different C. difficile strains isolated from hospitalized patients and carriage of cytolethal distending toxin gene (cdt) in different hospitals. Method C. difficile strains were isolated from stool samples of inpatients referred to a reference laboratory from different hospitals and also outpatients with diarrhea, during 2008–2011. DNA was extracted from pure culture of the bacterium and PCR was performed for tcdA, tcdB, tcdE, tcdC, tcdD, and cdu2 genes. Carriage of two binary toxin genes cdtA, cdtB was also determined in these strains. To find clonal strains, similarity of genotypes and integrity of PaLoc among the isolates was compared in each hospital. Results The intact PaLoc was found most frequently among the isolates in the outpatients (19/51, 37.2%, Group I), while incomplete PaLoc found mostly in patients who were hospitalized in the infectious diseases and internal diagnosis wards. tcdA and tcdB genes were detected in different combinations among the studied strains. These strains showed tcdA+B+, tcdA+B−, and tcdA−B+ genotypes in a frequency of 76.4% (39/51), 7.8% (4/51), and 17.6% (9/51), respectively. Analysis of gene composition of the PaLoc showed 19 distinct genotypes among the 51 strains. Accordingly, 38 strains were classified mainly into 6 regular groups, while the remaining strains showed heterogeneous patterns. tcdC−/tcdD− constituted the most common genotypic group among the strains with partial PaLoc (7/51, 13.7%). A hypertoxigenic genotype, tcdC−/tcdA+/tcdB+, was detected in 2 strains (2/51, 3.9%). The intact genotype was also detected in a C. difficile isolate from outpatients. Cdt encoding genes toxins was observed in low numbers of the strains (7/52, 13.5%). All of cdtA+B+ strains were belonged to PaLoc group 1 (intact genotype). Statistical analyses showed no correlation between particular genotypes and special wards of the hospitals (p value>0.05). Conclusion Collectively, our results showed diversity of C. difficile strains in most wards of the studied hospitals. Diversity of PaLoc genotypes in the strains that isolated from the same wards proposed endogenous routes of the infection, as common cause of CDI in these patients.

Successful clones of Acinetobacter baumannii cause a variety of nosocomial infections through serum resistance, biofilm formation, and antimicrobial resistance as virulence capabilities. Fifty clinical isolates of multidrug-resistant (MDR) A. baumannii were analyzed for clonal relatedness, serum resistance, biofilm formation, and in vivo assays. Furthermore, some virulence genes, sequence variation of ompA, and its expression were studied. The MLST (multilocus sequence typing) results showed that there were three sequence types among MDR isolates including ST2 (64%, 32/50), ST513 (30%, 15/50), and ST1 (6%, 3/50). The data showed that the clinical isolates recovered from sputum had mostly high biofilm-formation capacity, while isolates recovered from host interior fluids had high serum resistance. The results of PCR assays and in silico analysis represented patterns of virulence genes and even ompA sequence variations among MDR isolates which were clonally dependent. While quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that bacteremia-producing strains in C57/BL6 mice significantly overexpress ompA (P

Klebsiella pneumoniae is among the most important causes of urinary tract infection (UTI). The aim of this study was to investigate the prevalence and correlation of antibiotic resistance with virulence characteristics and genetic diversity in K. pneumoniae isolated from UTIs in Iran. Phenotypic tests and antibiotic susceptibility were carried out on the isolates. Detection of the virulence and extended-spectrum β-lactamase (ESBL) genes was performed by polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) was used for exploring the genomic relatedness. Hemolysin, biofilm, and hypermucoviscosity formation were observed in 87.1%, 86.4%, and 12.1% of isolates, respectively. The antibiotic resistance rate of K. pneumoniae isolates ranged from 12.1% for meropenem to 100% for amoxicillin. The prevalence of virulence genes ranged from 1.4% for cnf-1 to 100% for mrkD, fimH, kpn, and entB genes. In this study, 91.7%, 33.3%, and 4.2% of phenotypically ESBL-producers were positive for blaCTX-M, blaTEM, and blaSHV genes, respectively. An association was observed between the presence of traT, fyuA, or cnf-1 genes with antibiotic resistance. Two clone types were obtained by PFGE that indicate different K. pneumoniae clones in community- and hospital-acquired UTIs. The findings of this study are valuable in development of treatment strategies against UTIs in Iran.

Objectives Carbapenem-resistant Klebsiella pneumoniae infections are associated with increased rates of treatment failure and death. Several studies have reported isolates with a combined hypervirulent and antimicrobial-resistant phenotype. Methods In this study, the molecular characteristics of hypervirulent K. pneumoniae (hvKP) isolated from mechanically-ventilated patients admitted to a toxicological intensive care unit (ICU) in Tehran, Iran, were examined. String test, antimicrobial susceptibility testing, virulence factors analysis and plasmid replicon typing were performed. The clonal relatedness of the isolates was analysed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results hvKP accounted for 9.4% (5/53) of K. pneumoniae isolated from ventilator-associated pneumonia among patients admitted to the ICU with acute drug poisoning. The mortality rate was 7.5% (4/53) among K. pneumoniae-infected patients. All fatal K. pneumoniae were hvKP isolates, were resistant to imipenem and harboured an aacA7, blaVIM-2 and dhfrI cassette arrangement in a class 1 integron. The isolates were shown to be ST23 (Pasteur scheme) and exhibited similar PFGE patterns. Plasmid analysis revealed a class 1 integron harbouring blaVIM-2 located on an ca. 45-kb IncN plasmid. Conclusion Here we describe the emergence of VIM-2-producing hvKP serotype K1/ST23 in an outbreak with high mortality in a hospital toxicological ICU. It appears that we must alert and prepare the hospital’s surveillance system for the appearance, expansion and clinical importance of new K. pneumoniae clones associated with high antimicrobial resistance and robust virulence capabilities.

Carbapenem-resistant

The accurate identification of Acinetobacter spp. is challenging due to their high phenotypic and biochemical similarities. Because clinical relevance and antibiotic susceptibility are significantly different among different genomic species of Acinetobacter, the exact identification of A. baumannii is necessary and it can help us prevent inappropriate antibiotic use and inferior clinical care. This project employed a sequence-specific PCR assay for the rpoB region in A. baumannii to distinguish it from non-Acinetobacter baumannii Acinetobacter species. Moreover, a duplex PCR assay was used to detect blaOXA-51-like and gluconolactonase genes as a second identification method. In this study, 210 isolates of Acinetobacter spp. were considered and identified by PCR-sequencing of rpoB gene as a reference test. PCR-sequencing of rpoB revealed that 179 isolates were A. baumannii and 31 were non- A. baumannii Acinetobacter strains. PCR amplification targeting the rpoB gene as the first method, detected 182 isolates of A. baumannii, while duplex PCR assay confirmed 163 isolates as A. baumannii. Data analysis indicated that the sensitivities of sequence-specific PCR of the rpoB gene and duplex PCR assay were 100% and 91.06%, respectively, while specificities were 91.18% and 100%, respectively. Given the data, it was revealed that these two methods showed a reasonable potential for the accurate identification of A. baumannnii from non- A. baumannii species. Sequence-specific PCR assay for the rpoB gene and duplex PCR assay for blaOXA-51-like and gluconolactonase genes are rapid, reliable and cost-effective methods which can be used in clinical laboratories for the accurate identification of A. baumannii.

The prevalence of multiple sclerosis (MS) in the Persian Gulf countries has been significantly increasing during the past decades. This study was conducted for investigating the prevalence and incidence of MS in Northeast Iran (Khorasan Razavi province). This cross-sectional study was conducted during 1 January 1988 and 23 September 2018. All patients with a clinically definite diagnosis of MS according to the McDonald criteria (2005) and MRI along with the medical diagnosis, recorded in the Khorasan MS society, were considered for calculation of crude and age-standardized prevalence, and incidence rates of MS. The periodic incidence rates were calculated based on the year of onset of MS. Also, we calculated gender ratios for prevalence and incidence rates. The mean age-standardized prevalence and incidence rates of MS in the Khorasan Razavi were 8.69 (95% CI 8.05–9.41) per 100,000 (3.99 (95% CI 3.39–4.74) for males, 13.49 (95% CI 12.37–14.76) for females). Age-standardized prevalence was 48.87 (95% CI 48.37–49.35) per 100,000 (22.47 (95% CI 22.01–22.93) for males, 75.65 (95% CI 74.80–76.51) for females). Also, the mean incidence and prevalence for Mashhad County as capital of province were 11.38 and 59.09 per 100,000 populations, respectively. The female/male ratio was 3.33 for all age groups. Our results showed that this region is a high-risk area for MS like central region of Iran. Our results revealed that the prevalence and incidence of MS in the study area have increased during the recent decades with a sharp slope.

BACKGROUND Resistant Helicobacter pylori to commonly used antimicrobial agents are associated with severe upper gastrointestinal disorders. To provide an epidemiological picture of H pylori and characterize the resistance pattern and genetic variation of clinical isolates, stomach biopsies from patients with functional dyspepsia were evaluated in northeast of Iran. MATERIALS AND METHODS In this study, 80 patients were recruited. Finally, fifty H pylori strains were isolated from antrum and corpus biopsies by culturing on Columbia agar. All strains were identified by standard laboratory procedures. Susceptibility testing of antibiotics was performed using minimum inhibitory concentration test. Allele-specific primer (ASP)-PCR of 23S rRNA which associated with clarithromycin resistance was done among resistant strains. Moreover, cagA gene and polymorphism in vacA were detected. Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was applied to investigate the genetic variations among all strains. RESULTS Antibiotic resistance pattern of H pylori strains was as follows: 68% (34/50) to metronidazole, 50% (25/50) to rifampicin, 30% (15/50) to amoxicillin, 28% (14/50) to levofloxacin, 22% (11/50) to clarithromycin, and 16% (8/50) to tetracycline. Multidrug-resistant strains were observed in 19 strains (38%). ASP-PCR of 23S rRNA showed four strains had A2143G mutation, six strains had A2142G mutation, and one strain had a Wt+A2143G mutation. Amplification of virulence-associated genes revealed that cagA was present in 27 isolates (54%) and vacA in 36 isolates (72%). The most common genotype of H pylori was vacA s1am2 (40%) followed by vacA s2m2 (14%), vacA s1am1 (12%), vacA s1bm1 (4%), and vacA s1bm2 (2%). DNA fingerprinting pattern indicated a high heterogeneity among isolated strains. CONCLUSION An alarming level of resistance to metronidazole and rifampicin and high heterogeneity among H pylori isolates highlighted the importance of continued monitoring of antimicrobial susceptibility and epidemiological surveillance of this pathogen.

Clostridioides difficile is one of the major causatives of nosocomial infections worldwide. Antibiotic-associated diarrhea, pseudomembranous colitis, and toxic megacolon are the most common forms of C. difficile infection (CDI). Considering the high antibiotic resistance of C. difficile isolates and the low efficacy of immunization with toxin-related vaccines, we suggested that surface-exposed and secreted proteins could be considered as potential immunogenic targets against CDI. Various immuninformatics databases were used to predict antigenicity, allergenicity, B-cell epitopes, MHC-II binding sites, conserved domains, prevalence and conservation of proteins among the most common sequence types, molecular docking, and immunosimulation of immunogenic targets. Finally, 16 proteins belonging to three functional groups were identified, including proteins involved in the cell wall and peptidoglycan layer (nine proteins), flagellar assembly (five proteins), spore germination (one protein), and a protein with unknown function. Molecular docking results showed that among all the mentioned proteins, WP_009892971.1 (Acd) and WP_009890599.1 (a C40 family peptidase) had the strongest interactions with human Toll-like receptor 2 (TLR-2) and TLR-4. This study proposes a combination of C. difficile toxoid (Tcd) and surface-exposed proteins such as Acd as a promising vaccine formulation for protection against circulating clinical strains of C. difficile.

A new binder free electrode based on ternary copper nickel cobalt oxide nanowires grown on the carbon cloth (CuNiCoO4 NWs@ carbon cloth) was prepared and characterized by field emission scanning electron microscopy (FE-SEM), x-ray diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDX), and cyclic voltammetry (CV). The prepared electrocatalyst was directly used for electrochemical sensing of glucose without using enzyme. The effect of different parameters such as potential scan rate, switching potential, and glucose concentration on the electrochemical oxidation of glucose was investigated. The results showed that such an electrode presents excellent catalytic activity toward the oxidation of glucose in aqueous alkaline solution. Under optimum conditions, the potential application of the electrode was evaluated by applying it to the analytical determination of glucose concentration. The results revealed that the electrocatalytic current increased linearly with the glucose concentration in the range from 0.02 to 1.4 mM with a low detection limit of 6.5 μM and good sensitivity of as high as 1782 μA mM−1 cm−2. Selectivity investigations demonstrate that the CuNiCoO4 NWs@CC electrode could be used for selective detection of glucose in the presence of interfering species. Real sample analysis shows reasonable RSD values implying negligible matrix effect in determination of glucose in human serum samples.

Objective: Diabetes mellitus (DM) is the most common metabolic disorder that defined by chronic hyperglycemia for the deficiency in insulin secretion or resistance. Hyperglycemia could induce non-enzymatic glycation of proteins. It has been suggested that some traditional plants can improve blood glucose and inhibit glycation process. This work evaluates and compares the anti-glycation activities of four Iranian plant extracts in vitro. Methods: The methanolic extract of "Fumaria officinalis, Stachys lavandulifolia, Salvia hydrangea and Rosa Damascene" was prepared in three different concentrations. Phenolic, flavonoids content and antioxidant activity were evaluated. The multistage glycation markers- fructosamines (early stage), protein carbonyls (intermediate stage) and squared minus aggregation of albumin were investigated in the bovine serum albumin (BSA)/ glucose systemt. Results: All plants showed the high potency of scavenging free radicals and glycation inhibition in the following order: Fumaria officinalis > Rosa Damascene > Stachys lavandulifolia > Salvia hydrangea. There was a significant correlation between antioxidant and anti-glycation activity. Also, the antioxidant and anti-glycation capacity of extracts correlated with total phenolic and flavonoids content. Conclusion: Our findings demonstrated that the studied plants are good sources of anti-glycation and antioxidant compounds and, these properties can primarily attributable to phenolics, particularly flavonoids. © 2018 Korean Pharmacopuncture Institute.

In the current study, we synthesized new vanadyl complexes of the N,N′-dipyridoxyl(1,2-propanediamine) Schiff bases and characterized them by experimental and theoretical methods. Also, the antibacterial (against strains of S. aureus, P.aeruginosa and E. coli) and cytotoxicity activities of three V(IV) complexes including VO-EN, VO-13 and VO-12 of the pyridoxal SBs were evaluated against human prostate tumor cells (PC3 cell line), where the VO-EN, VO-13 and VO-12 species are V(IV) complexes of the N,N′-dipyridoxyl(ethylenediamine), N,N′-dipyridoxyl(1,3-propanediamine) and N,N′-dipyridoxyl(1,2-propanediamine) Schiff bases, respectively. Deprotonated form of the N,N′-dipyridoxyl(1,2-propanediamine) Schiff base acts as a tetradentate N2O2 ligand, which coordinates to the V(IV) via two phenolate oxygens and two azomethine nitrogens. In the square-pyramidal geometry of the synthesized complex (VO-12), an oxo ligand occupies the apical position. The analyzed results for the VO-12 complex were in agreement with the experimental tests, confirming the suitability of its optimized geometry. The synthesized VO-12 complex displays significant and reusable catalytic activities in synthesis of the tetrahydrobenzo[b]pyrans, where the V4+ central ion is the active site of the catalyst. All investigated SB complexes were active against P.aeruginosa, while VO-13, VO-12 and VO-EN complexes revealed no activity against E. coli and S. aureus, respectively. All complexes showed considerable cytotoxic against PC3 cells. Our results suggested that these complexes decreased the cell viability after 48 h and the VO-12 complex showed the highest cytotoxicity. These observations suggested that the VO-EN, VO-13 and VO-12 species can be cytotoxic materials for pharmaceutical applications. In addition, in a dose-dependent manner, these compounds can be consider as potent antimicrobial agents.

Introduction: Acinetobacter baumannii as a Gram-negative coccobacillus has become a major cause of hospital-acquired infections. The virulence factors involved in serum resistance are important targets in the development of an effective vaccine against this pathogen. Our aim in this project was in silico analyses of A. baumannii proteins involved in serum resistance which could potentially be used as efficient vaccines. Methods: Based on computational procedures, we evaluated all A. baumannii proteins involved in serum resistance, namely AbOmpA, PKF, PLD , PBP 7/8, CipA and Tuf SurA1, as vaccine candidates. Subcellular localization, sequence conservation, domain prediction and 3D modelings were analyzed by online tools. Moreover, the prevalence of serum resistance factors in 5 strains of A. baumannii was characterized. The MHC-binding sites of class I and II were detected. Linear and conformational B cell epitopes were analyzed by 2 prediction servers. Results: The MetaLocGramN server showed that AbOmpA, PKF, PBP7/8, phospholipase D, CipA, Tuf and SurA1 were outer membrane protein (56.32%), extracellular protein (58.74%), extracellular protein (52.59%), cytoplasmic protein (45.08%), extracellular protein (53.8%), Cytoplasmic protein (96.36%) and extracellular protein (58.23%), respectively. The OMD of AbOmpA, PKF, PBP7/8 and phospholipase D, CipA, Tuf and SurA1 were 0.060, 0.076, 0.08, 0.101, 0.09, 0.06 and 0.103, respectively. The numbers of immunogenic linear and conformational epitopes with high score (P ≥ 0.6), extracted from beta-barrel of AbOmpA were 6 and 4; whereas these values for PKF were 10 and 4, respectively. Conclusion: The in silico analyses and reverse vaccinology criteria showed that AbOmpA and PKF had better attributes as vaccine targets and they could be considered as promising vaccine candidates against A. baumannii.

SummaryIt is generally assumed that the allocation and synthesis of total cellular resources in microorganisms are uniquely determined by the growth conditions. Adaptation to a new physiological state leads to a change in cell size via reallocation of cellular resources. However, it has not been understood how cell size is coordinated with biosynthesis and robustly adapts to physiological states. We show that cell size inEscherichia colican be predicted for any steady-state condition by projecting all biosynthesis into three measurable variables representing replication initiation, replication-division cycle, and the global biosynthesis rate. These variables can be decoupled by selectively controlling their respective core biosynthesis using CRISPR interference and antibiotics, verifying our predictions that different physiological states can result in the same cell size. We performed extensive growth inhibition experiments, and discovered that cell size at replication initiation per origin, namely the initiation mass or “unit cell,” is remarkably invariant under perturbations targeting transcription, translation, ribosome content, replication kinetics, fatty acid and cell-wall synthesis, cell division, and cell shape. Based on this invariance and balanced resource allocation, we explain why the total cell size is the sum of all unit cells. These results provide an overarching framework with quantitative predictive power over cell size in bacteria.

Clostridioides difficile and Staphylococcus aureus are two well-known pathogens both causing hospital- and community-acquired infections. However, their intestinal coexistence was not well investigated in inflammatory bowel disease (IBD). Herein, we explored the prevalence of C. difficile, S. aureus and their coexistence in the gut of Iranian patients with IBD. Fecal and colon specimens were obtained from 70 outpatients with underlying IBD, and investigated for the presence of C. difficile and S. aureus. C. difficile isolates were characterised by CE-ribotyping. PCR was used for detection of toxin-encoding genes of C. difficile and S. aureus isolates. The antimicrobial susceptibility testing of C. difficile and S. aureus isolates were examined by agar dilution and Kirby-Bauer disk diffusion methods, respectively. Totally, C. difficile and S. aureus were detected in only 5.7% and 15.8% of IBD flares. Coexistence of C. difficile and S. aureus was detected in 5.7% of IBD flares. Two different C. difficile ribotypes including RT 126 and RT 017 were identified showing toxin profiles of tcdA+B+/cdtA+B+ and tcdA+B+, respectively. In S. aureus isolates, only positivity for the presence of sea enterotoxin was detected. C. difficile isolates were susceptible to metronidazole, ceftazidime and fidaxomicin. The highest resistance of S. aureus isolates was observed against penicillin (92.3%), following amoxicillin-clavulanate (38.5%) and amikacin (30.8%). Our findings demonstrated that patients with IBD flare are more sensitive to acquire coinfection of C. difficile and S. aureus than remission. However, more robust data is required to study the crosstalk between these enteric infections and their clinical relevance in patients with IBD flare.

Colistin is drug of choice for treatment of carbapenem-resistant Acinetobacter baumannii infections. Unfortunately, global increase in clinical outbreaks of colistin and carbapenem resistant A. baumannii infections is on the rise and cause public health concern. In the present study, a total of 187 A. baumannii recovered from specimens of 240 patients admitted to intensive care units (ICUs) of two hospitals in Kerman, Iran during 2017–2018. Among the isolates, we found four extensive drug-resistant (XDR) with Minimum Inhibitory Concentration (MIC) ≥4 μg/mL against colistin. The colistin-resistant (Col-R) isolates harbored blaOXA–51 and blaOXA-23 carbapenemase genes, exhibited resistance to all antibiotic classes except tigecycline and ampicillin-sulbactam. They belonged to clonal complex 2, a new MLST type 1752 and displayed identical RAPD-PCR fingerprints. Phylogenetic tree analysis suggested that, the Col-R A. baumannii emerged by endogenous mutations rather than acquisition of preexisting clones. Expressions of pmrCAB by quantitative real-time PCR (qRT-PCR) revealed 8 and 7 folds increased in the transcription levels of pmrB/C genes in strain 1 grown in presence of 16 μg/mL colistin (p ≤ 0.01). However, no change in the expression of the pmrA was observed. Furthermore, DNA sequencing of Col-R genes illustrated three nonsynonymous substitutions in the LpxA (N136 → K), LpxC (P293 → Q), and PmrB (V21 → F, S28 → R, I149 → F) in the strains 1 and 3, respectively showing MIC 32 μg/mL against colistin. Multiple amino acids alignments demonstrated several substitutions in N-terminal region of PmrB. In conclusion, the above results provide valuable insights into the mechanism of Col-R in A. baumannii and the expressions of relative genes.

Infections and outbreaks caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) are prevalent and have been reported worldwide over the past 20 or more years. Class 1 integron in MDR-AB plays an important role in the spread of antibiotic resistance in clinical settings. This study has been conducted to evaluate the detection of metallo-β-lactamase, characterization of class 1 integron and determination of clonal relatedness among A. baumannii hospital isolates. Sixty-five clinical isolates of MDR-AB were recovered from two Iranian hospital's intensive care units from February to August 2013. Integrase (intI1) and blaIMP genes were detected in 70.8 % (n=46/65) and 9.23 % (n=6/65) of the isolates using PCR assay, respectively. No other metallo-β-lactamase genes (blaVIM, blaSIM and blaNDM) were detected. PCR sequencing of integron gene cassette revealed the following arrays: blaOXA10-aacA4-blaIMP-55-cmlA5 (as a novel array was designated In1243), aacC1 and aadA1. Analysis of blaIMP gene revealed a new allele designated as blaIMP-55. Gene transfer experiment by conjugation showed the 36 kb conjugative plasmid harbouring In1243. The clonal assessment by repetitive extragenic palindromic PCR demonstrated a high-degree relatedness among the strains, but strains harbouring In1243 displayed a different repetitive extragenic palindromic PCR profile. In this study, we found that a novel class 1 integron (In1243) that encoded a new blaIMP allele resided on a transferable plasmid in non-clonal strains of MDR-AB.

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. MIC50 and MIC90 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.

Background:: One of the most challenging isolates in nosocomial infections is Acinetobacter baumannii which is rapidly changing towards multi-drug resistant. Resistance to the last resort antibiotics, carbapenems, is reported around the world. In particular, metallo-β-lactamases (MBL) are responsible and detection of MBLs is of interest. Objectives:: In this study we have evaluated the prevalence of MBLs in A. baumannii isolated during 2012 by two feasible described methods. Materials and Methods:: In this cross sectional study, during 2012, 40 A. baumannii non-replicate isolates gathered from clinical and environmental specimens from Afzalipur hospital of Kerman. Isolates were characterized by conventional biochemical tests as A. baumannii-calcoaceticus complex (ABC). For antimicrobial susceptibility testing, 17 different antibiotics were sought by agar diffusion method. Phenotypic MBL detection was assessed by double disk test and Modified Hodge test for carbapenem resistant isolates. Results:: During the study 40 isolates of ABC were collected. Of which, 23 (57%) isolates were resistant to carbapenems. Phenotypic MBLs detection was negative by two methods. Conclusions:: The rates of resistance of the isolated ABCs in our clinical setting were at high level. Though, carbapenems were the most efficient antibiotic, but, there was a pronounced rate of resistant. MBL genes were not responsible for carbapenem resistance in under study clinical setting.

Acinetobacter baumannii is an important nosocomial pathogen which causes a wide range of infections. In this study, we addressed the role of class 1 integron, ISAba1 and ISAba125 associated with antimicrobial resistance in 72 clinical isolates of A. baumannii collected from clinical settings in Tehran, Iran. Moreover, to study the clonal relatedness of strains, repetitive extragenic palindromic-PCR (rep-PCR) assay was carried out. PCR revealed that blaOXA-51-like, blaOXA-23-like, blaOXA-24/40-like, blaOXA-58-like, blaNDM, integrase gene (intI1), ISAba1, and ISAba125 were present in 86.11% (62/72), 84.72% (61/72), 30.55% (22/72), 0% (0/72), 0% (0/72), 58.33% (42/72), 97.22% (70/72), and 65.27% (47/72) of the strains, respectively. Sequencing of 39 internal variable regions of class 1 integrons showed seven gene cassette arrays, including aadA4-catB8-aadA1 (2.77%), aadA1-aadA4 (1.38%), aacC4-aadA1 (2.77%), aacC4 (22.22%), aadA1 (13.88%), aadA4 (5.55%), and catB8 (5.55%). We detected ISAba1 in the upstream of blaOXA-23-like, blaOXA-51-like, and blaADC in 54.16% (39/72), 9.72% (7/72), and 56.94% (41/72) of the strains, respectively. Whereas, there was a low frequency of disruptions in carO and dacD genes: 5.55% (4/72) and 4.16% (3/72). Rep-PCR analysis revealed that the isolates were genetically diverse. However, Cl-12 and Cl-15 were the largest clusters and they were recovered from various hospitals. Our analysis showed the high rates of class 1 integrons as a repertoire of aminoglycoside-modifying enzymes. It seems that linkages of ISAba1-blaOXA-23-like and ISAba1-blaOXA-69, and disruptions in carO or dacD can develop resistance to carbapenems among clinical isolates of A. baumannii.

Sixty-five MDRAB isolates from clinical samples were collected. Molecular typing was carried out by random amplified polymorphism DNA polymerase chain reaction (RAPD-PCR). Biofilm formation was assayed by the microtiter method.The sequence ofThe results suggest that

Transactional memory represents an attractive conceptual model for programming concurrent applications. Unfortunately, high transaction abort rates can cause significant performance degradation. Conventional transactional memory realizations not only pessimistically abort transactions on every read-write conflict but also because of false sharing, cache evictions, TLB misses, page faults and interrupts. Consequently, the use of transactions needs to be restricted to a very small number of operations to achieve predictable performance, thereby, limiting its benefit to programming simplification. In this paper, we investigate snapshot isolation transactional memory in which transactions operate on memory snapshots that always guarantee consistent reads. By exploiting snapshots, an established database model of transactions, transactions can ignore read-write conflicts and only need to abort on write-write conflicts. Our implementation utilizes a memory controller that supports multiversion memory, to efficiently support snapshotting in hardware.We show that snapshot isolation can reduce the number of aborts in some cases by three orders of magnitude and improve performance by up to 20x.

Metallo-β-lactamases (MBLs) such as IMPs are broad-spectrum β-lactamases that inactivate virtually all β-lactam antibiotics including carbapenems. In this study, we investigated the hydrolytic activity, phylogenetic relationship, three dimensional (3D) structure including zinc binding motif of a new IMP variant (IMP-55) identified in a clinical strain of Acinetobacter baumannii (AB). AB strain 56 was isolated from an adult ICU of a teaching hospital in Kerman, Iran. It exhibited MIC 32μg/ml to imipenem and showed MBL activity. Hydrolytic property of the MBL enzyme was measured phenotypically. Presence of blaIMP gene encoded by class 1 integrons was detected by PCR-sequencing. Phylogenetic tree of IMP protein was constructed using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and 3D model including zinc binding motif was predicted by bioinformatics softwares. Analysis of IMP sequence led to the identification of a novel IMP-type designated as IMP-55 (GenBank: KU299753.1; UniprotKB: A0A0S2MTX2). Impact in term of hydrolytic activity compared to the closest variants suggested efficient imipenem hydrolysis by this enzyme. Evolutionary distance matrix assessment indicated that IMP-55 protein is not closely related to other A. baumannii IMPs, however, shared 98% homology with Escherichia coli IMP-30 (UniprotKB: A0A0C5PJR0) and Pseudomonas aeruginosa IMP-1 (UniprotKB: Q19KT1). It consisted of five α-helices, ten β-sheets and six loops. A monovalent zinc ion attached to core of enzyme via His95, His97, His157 and Cys176. Multiple amino acid sequence alignments and mutational trajectory with reported IMPs showed 4 amino acid substitutions at positions 12(Phe→Ile), 31(Asp→Glu), 172(Leu→Phe) and 185(Asn→Lys). We suggest that the pleiotropic effect of mutations due to frequent administration of imipenem is responsible for emergence of new IMP variant in our hospitals.

Programming language and operating system support for efficient concurrency-safe access to shared data is a key concern for the effective use of multi-core processors. Most research has focused on the software model of multiple threads accessing this data within a single shared address space. However, many real applications are actually structured as multiple separate processes for fault isolation and simplified synchronization. In this paper, we describe the HICAMP architecture and its innovative memory system, which supports efficient concurrency safe access to structured shared data without incurring the overhead of inter-process communication. The HICAMP architecture also provides support for programming language and OS structures such as threads, iterators, read-only access and atomic update. In addition to demonstrating that HICAMP is beneficial for multi-process structured applications, our evaluation shows that the same mechanisms provide substantial benefits for other areas, including sparse matrix computations and virtualization.

Scaling the performance of a power limited processor requires decreasing the energy expended per instruction executed, since energy/op * op/second is power. To better understand what improvement in processor efficiency is possible, and what must be done to capture it, we quantify the sources of the performance and energy overheads of a 720p HD H.264 encoder running on a general-purpose four-processor CMP system. The initial overheads are large: the CMP was 500 x less energy efficient than an Application Specific Integrated Circuit (ASIC) doing the same job. We explore methods to eliminate these overheads by transforming the CPU into a specialized system for H.264 encoding. Broadly applicable optimizations like single instruction, multiple data (SIMD) units improve CMP performance by 14 x and energy by 10x, which is still 50x worse than an ASIC. The problem is that the basic operation costs in H.264 are so small that even with a SIMD unit doing over 10 ops per cycle, 90% of the energy is still overhead. Achieving ASIC-like performance and effciency requires algorithm-specifc optimizations. For each subalgorithm of H.264, we create a large, specialized functional/storage unit capable of executing hundreds of operations per instruction. This improves energy effciency by 160x (instead of 10x), and the final customized CMP reaches the same performance and within 3x of an ASIC solution's energy in comparable area.

Because of technology scaling, power dissipation is today's major performance limiter. Moreover, the traditional way to achieve power efficiency, application-specific designs, is prohibitively expensive. These power and cost issues necessitate rethinking digital design. To reduce design costs, we need to stop building chip instances, and start making chip generators instead. Domain-specific chip generators are templates that codify designer knowledge and design trade-offs to create different application-optimized chips.

In this paper, we examine the area-performance design space of a processing core for a chip multiprocessor (CMP), considering both the architectural design space and the tradeoffs of the physical design on which the architecture relies. We first propose a methodology for performing an integrated optimization of both the micro-architecture and the physical circuit design of a microprocessor. In our approach, we use statistical and convex fitting methods to capture a large micro-architectural design space. We then characterize the area-delay tradeoffs of the underlying circuits through RTL synthesis. Finally, we establish the relationship between the architecture and the circuits in an integrative model, which we use to optimize the processor. As a case study, we apply this methodology to explore the performance-area tradeoffs in a highly parallel accelerator architecture for visual computing applications. Based on some early circuit tradeoff data, our results indicate that two separate designs are performance/area optimal for our set of benchmarks: a simpler single-issue, 2-way multithreaded core running at high-frequency, and a more aggressively tuned dual-issue 4-way multithreaded design running at a lower frequency.

Resistance-nodulation-division efflux system (RND) adeABC contributes to intrinsic resistance to various drug classes in Acinetobacter baumannii. Similarly, quorum sensing (QS) plays an important role in the biofilm formation and pathogenicity of this bacterium. The aims of this study were to evaluate the influence of iron limitation on the expression of efflux pump (adeABC) genes and QS (luxI, luxR) system by relative quantitative real-time polymerase chain reaction (qRT-PCR). In addition, DNA sequence and phylogenetic relatedness of biofilm-associated protein (Bap) gene was also investigated. Sixty-five multidrug-resistant isolates of A. baumannii were recovered from ICU patients of three hospitals in Kerman, Iran. The isolates were highly resistant to at least 11 antibiotics (MIC ≥64 μg/mL); however, 87% and 89% were susceptible to colistin and tigecycline, respectively (MIC 0.05 μg/mL) (p ≤ 0.05). We detected the presence of RND efflux pump, QS, and bap genes with the frequencies of 92% (adeA), 61.5% (adeB), 84.6% (adeC), 80% (luxI), 61% (luxR), and 66% (bap), respectively. qRT-PCR analysis showed that in some isolates, expression of both adeABC and luxI/R was increased more than fourfold in the presence of low iron (20 μm), suggesting the additional regulatory role of iron on both efflux pump and QS system. Alignment and phylogenetic analysis on the strong biofilm forming isolates confirmed that the fragments amplified were indeed part of bap gene and deduced sequence was similar to A. baumannii K9B410.