حوراء ناطق كبروت الفتلاوي

Abstract Multidrug-resistant (MDR) Pseudomonas aeruginosa has emerged as a significant clinical threat due to its high resistance to multiple antibiotic classes and the limited effectiveness of current therapeutic options. This study aimed to evaluate selected coumarin and indole derivatives targeting the MexB and GyrB proteins of MDR P. aeruginosa using an integrated in silico approach, supported by molecular characterization of clinical isolates. A total of 44 clinical P. aeruginosa isolates recovered from sputum, urine, wound swabs, and burn swabs were examined for antimicrobial susceptibility, revealing extensive drug resistance. Complete resistance (100%) was observed against amoxicillin-clavulanic acid (AMC), cefotaxime (CTX), and trimethoprim-sulfamethoxazole (SXT). Resistance rates were 97.7% for ticarcillin-clavulanic acid (TIM), 88.63% for amikacin (AK), 60% for imipenem (IMP) and meropenem (MEM), and 52.27% for ciprofloxacin (CIP) and levofloxacin (LEV). PCR analysis confirmed the presence of the GyrB and MexB genes in all isolates. Representative PCR-positive isolates were sequenced and verified by BLAST analysis. The nucleotide sequence of the GyrB gene has been deposited in the DDBJ under accession number LC919849, and the corresponding protein sequence was assigned GenBank accession number BHR60112.1. Molecular modeling and structural validation of the GyrB and MexB proteins were performed prior to molecular docking analysis. Novobiocin and PAbN were selected as reference inhibitors for GyrB and MexB, respectively, while coumarin- and indole-based compounds were evaluated as candidate ligands. Docking analysis revealed strong predicted binding affinities for novobiocin (-10.2 kcal/mol) and PAbN (-8.1 kcal/mol). The coumarin derivative exhibited favorable predicted interactions within the ATP-binding pocket of GyrB, whereas the indole derivative demonstrated favorable predicted binding within the substrate-binding cavity of MexB. ADMET and toxicity analyses indicated favorable predicted drug-likeness for both compounds, with high gastrointestinal absorption, no bioavailability violations, and a score of 0.55. However, the indole derivative showed a positive AMES test prediction, indicating potential mutagenic liability. Molecular dynamics simulations demonstrated the structural stability of the modeled MexB protein over a 25 ns simulation period. Overall, these findings provide preliminary in silico evidence supporting further investigation of coumarin and indole derivatives as candidate compounds targeting GyrB and MexB in MDR P. aeruginosa. Keywords: MDR Pseudomonas aeruginosa, Targeting GyrB and MexB, Efflux Pump Inhibition, In Silico Drug Discovery, Antibacterial Agents, Coumarin Derivatives, Indole Derivatives, Molecular Modeling

Background: Carbapenem‑resistant Klebsiella pneumoniae (CRKP) represents a major clinical challenge due to the accumulation of multiple antimicrobial resistance mechanisms. DNA gyrase subunit B (gyrB) has emerged as an attractive antibacterial target. Methods: A total of 314 clinical specimens; 54 K. pneumoniae isolates were identified, including 41 multidrug‑resistant (MDR) carbapenem‑resistant strains (75.9%). Antimicrobial susceptibility testing and polymerase chain reaction‑based molecular screening were performed, followed by sequencing and phylogenetic analysis of the gyrB gene, including submission of a representative clinical isolates to deoxyribonucleic acid Data Bank of Japan (Accession No. LC918550). Results: CRKP isolates exhibited extensive multidrug resistance (41MDR isolates) associated with a complex resistance gene profile including blaIMP (100%), blaNDM‑1 (36.5%), blaOXA‑48‑like (26.8%), blaKPC (12.19%), blaCTX‑M (100%), blaSHV (100%), and the Class 1 integron integrase gene int1 (100%). Housekeeping genes (gyrB, 16 S ribosomal DNA [16S rDNA]) were detected in all isolates. Structural modeling revealed a high‑quality and reliable gyrB structure, with 97.42% of residues located with favored regions of the Ramachandran plot. Molecular docking predicted favorable and preferential binding of SPR719 to a conserved Adenosine triphosphatase (ATPase) pocket of gyrB with a high binding affinity (−9.8 kcal/mol), involving several conserved residues within the ATPase pocket. Molecular dynamics (MD) simulation of the apo‑gyrB protein demonstrated structural stability, compactness, and dynamic equilibrium throughout the 25 ns simulation period, with Root mean square fluctuation (RMDS) values stability after approximately 6–8 ns under physiological conditions. Conclusions: The principal contribution of this study lies in integrating clinical resistance profiling with gyrB sequence‑based conservation analysis and structural modeling, molecular docking and MD simulations in CRKP clinical isolates. The findings demonstrated that the gyrB ATPase pocket remains highly conserved despite the widespread presence of Carbapenemase and Extended spectrum β‑lactamases resistance determinants. Structural modeling revealed a high‑quality GyrB structure, while molecular docking indicated favorable binding of SPR719 within the ATPase pocket. MD simulations further supported the structural stability and conformational integrity of the modeled gyrB protein under physiological conditions. Collectively, these findings provide a molecular framework for future experiment investigations of GyrB‑targeted therapeutic strategies against multidrug‑resistant K. pneumoniae. Keywords: Deoxyribonucleic acid gyrase subunit B, integrons, carbapenem‑resistant Klebsiella pneumoniae, molecular docking, molecular dynamics simulations, SPR719, structure‑based antimicrobial discovery

Abstract Background: Acinetobacter baumannii is a multidrug-resistant opportunistic pathogen implicated in hospital-acquired infections, particularly in immunocompromised populations. Its association with respiratory complications in childhood asthma poses significant treatment challenges owing to resistance mechanisms mediated by genes such as gyrA (fluoroquinolone resistance), intrinsic blaOXA-51 (a species marker), and acquired blaOXA-23 (carbapenem resistance). Objective: The Aim of the present study to isolate A. baumannii from pediatric asthma patients and characterize the prevalence of gyrA, blaOXA-51, and blaOXA-23 resistance genes. Methodology: A total of 250 sputum samples were collected from asthmatic children at the Al-Zahraa Teaching Hospital, Iraq (November 2024–April 2025). Isolates were identified using VITEK®2, CHROM agar, and biochemical tests. PCR amplification targeted gyrA, blaOXA-51, and blaOXA-23 genes. Antimicrobial susceptibility was assessed according to CLSI guidelines. Results: Thirty-six A. baumannii isolates were identified in this study. All the isolates (100%) harbored gyrA and blaOXA-51, whereas blaOXA-23 was detected in 22% of the isolates. High resistance rates (100%) were observed to cefotaxime, ertapenem, and colistin. Conclusion: The high prevalence of gyrA and carbapenems genes underscores the dominance of multidrug-resistant A. baumannii in pediatric asthma patients. These findings highlight the urgent need for molecular diagnostics and antimicrobial stewardship to mitigate treatment failures and nosocomial transmission.

Typhoid fever is a paramount reason for horribleness that more mortal sin “around the sum ages aggregations clinched alongside iraq it initiated by salmonella typhi. Salmonella typhi is diagnosed serologically by the Widal test and confirmed by vitek and using polymerase chain reaction (PCR) based amplification of DNA from the bacterial samples of typhoid fever patients. The present study was designed to detect class I integron gene encoding antimicrobial of S. typhi using appropriate primers by PCR. These isolates of this study were collected from postgraduate laboratories (Prepared samples in vitro prepared diagnostics), they were a previous collected from carried out in Al Najaf provenance, throughout those period from July 2018 on March 2019 including 231 cases from blood, stool samples collected from patients suffering from typhoid fever were attended to Al-Sader Medical City and Al-Hakim General Hospital in Al-Najaf province. Biochemically tests and monovalent antisera gave 117 (50.64%) positive result S. typhi isolates and confirmed by Vitek system and PCR which showed positive result 59 (50.42%). Fifty nine isolates of S. typhi, were collected from patients with typhoid fever that distributed to 40/59 (34 %) from blood , 19/59 (15.1%) stool. Molecular detection revealed that most isolates of S. typhi were positive results to (intI) gene 43/59 isolate (the specific primer (intI) gene for S. typhi bacteria was designed in this study by using bioinformatics programs with NCBI website). According to the different diagnostic above, Vitek and PCR method were more sensitivity technique for S. typhi detection among typhoid patients. The results of virulence factors of S.typhi isolates were negative results for gelatinase, hemolysin, protease and capsulated. Multidrug resistance (MDR) of S. typhi isolates were represented by 18 antibiotics resistance to class and sub class of antibiotic. All S. typhi isolates appeared high resistance 100% to Aztreonam (AZM15), Nitrofurantion (F), Amoxicillin/clavulanicacid (AMC30), (PY25), Clarithromycin (CLR), Cefoxitin (FOX30), Penecillin(P10), Cefotaxime (CTX30), ampicillin (AMP), Meropenem (MEM), Tetracycline(TE30). Also resistance of isolates that revealed 91% to Impinem (IP ), 88% Ampicillin (AM10), 85%Amoxillin (AX), 81% Gentamicin (CN10), 80% Chloramphenicol (C30), 74% Cefpirome (CPR) and 68% Carbenicillin (CB).

hemolysin" ORIGIN 1 gttccaatca tgcagtccgg ctacaggggg agttgctgtt caccccgctg gggggcgtcg 61 atgacccggc cttctatcag gtgatggagc gggtcgacag cctggaaggg cagggcaaac 121 gccacaagcg ctcgctgacc cagccgcctg ccgccgaggc cggtctgccc cacgtggcct 181 tctacctcaa cgtcaaccgc aagatcagcg atgccgagtg caccttcccg cgctcgcgca 241 cctggaatcg gggtgatcgg ctgttctgcg attcgccgaa catctcgctg gtctaccggg 301 tcaacctgga gcgctccctg caatttggca acaccggttc cgccacgccg gatgccaaga 361 tagtgcggat ctcgctggac gaagagtcgg ccggtgccgg catccagctc aacgaggatc 421 tcagctggag cgagaacatc gcggactacc tgctgctgga cggctgggcc cgcgactatg 481 ccaccgatgc catcgctcag gattatcgct tcagcatcga ggcgtccaac accaaggcgg 541 cggtgctcaa gagcctgccg accaacctca acagcaagta tgagcatcgc gagatctcgg 601 gcttcgaggt gggggtcacc ggcggggtcg aggtgaacaa ggatgggccc aaggccaagc 661 tggaggcctc ggccaagttc agccagcagc gccagctcgc cacaaccccc cggggaaaaa 721 aaatatgaag aatacttt

The current study includes the detection of Staphylococcus aureus and Staphylococcus epidermis isolates causing the conjunctivitis. Bacterial conjunctivitis has a worldwide distribution, affecting persons of all ages and both genders.The study aimed to determine the role of bacteria in causing conjunctivitis, and determination of antibiotic susceptibility pattern .Thus 108 conjunctival swabs were collected from patients suffering from conjunctivitis were attended to Al-Sader Medical City and Al-Hakim General Hospital in Al-Najaf province during From July 2018 to December 2018. These isolates were diagnosed by four methods as (Culture method , biochemical tests, VITEK@2GP cards system and Polymerase chain reaction (PCR) technique). The VITEKitek@2GP cards system and PCR method of 16SrDNA gene was the best methods for diagnosis, which have led to isolate and diagnosis of 36(100%) isolate Staphylococcus aureus and Staphylococcus epidermis were distributed as 34 isolate of S.aureus and two isolate of S.epidermis. Multidrug resistance (MDR) of Staphylococcus aureus and Staphylococcus epidermis isolates were represented by resistance to ten sub class of antibiotic. All isolates appeared resistance to (Penicillin class) Carbenicillin, Ampicillin, Bacitracin and Penicillin(100%). The study also revealed a high rates of resistance to Cephalosporins that represented by, Cefotaxime and Cefoxitin (100%).Resistance to β-lactam/β-lactamase inhibitor combinations including Amoxicillin-Clavulanic acid (100%), Also high resistance to Vancomycin(100%).The results of resistance isolates appeared high resistance to Meropenem (100%) of Carbapenem class were effective against the majority of S.aureus and S.epidermis isolates. We showed that the PCR technique has been used to amplify qac, intI and 16SrRNA diagnostic genes of genomic DNA of all isolates Staphylococcus aureus , Staphylococcus epidermis and E.coli. Genomic DNA were extracted from all isolates. The results of all isolates diagnosis by PCR technique for qac 19/34(55%), intI 26/43(60%) and 16SrRNA detection clarified that 34/34(100%) isolates of Staphylococcus aureus.

ألقت التدريسية في كلية الطب بجامعة الكوفة الاستاذ المساعد الدكتور حوراء ناطق كبروت محاضرات متنوعة حول ( الاعتماد البرامجي ،التقييم الذاتي ، وادارة الجودة وتحسينها ) بالاضافة الى ادارة مجموعة من ورش العمل حول المعايير البرامجية الوطنية لاعتماد التقنيات الصحية والطبية بالتعاون مع اعضاء المجلس الوطني للاعتماد. وكانت الدورة التدريبية التي شاركت فيها كبروت ضمن مشاريع وزارة التعليم العالي والبحث العلمي / جهاز الاشراف والتقويم العلمي بأعداد فرق المقييم الوطني لمجالس الاعتماد المرتبطة بجهاز الاشراف خلال الفترة 12- 27 / 11 / 2023.

الناشر : موقع كلية الطب - جامعة الكوفة .................................................................................... حضرت التدريسية في كلية الطب/ فرع الاحياء المجهرية (د. حوراء ناطق كبروت) اجتماع المجلس الوطني لاعتماد برامج كليات التقنيات الصحية والطبية في وزارة التعليم العالي والبحث العلمي / جهاز الاشراف والتقويم العلمي / قسم الاعتماد بحضور رئيس واعضاء المجلس الوطني للاعتماد. الدكتورة كبروت تنسبت من مركز الوزارة الى فرع الاحياء المجهرية الطبية بكليتنا ضمن التعيينات الجديدة لحملة الدكتوراه في العام الحالي، بالإضافة الى مهامها المستمرة في المجلس الوطني للاعتماد/ جهاز الاشراف. كما ان الدكتورة كبروت تعد أحد الاعضاء المؤسسين للمجلس الوطني للاعتماد منذ عام ٢٠١٧ وتولت مقررية المجلس في العام ٢٠٢١ والى الان تزاول مهامها