No abstract

In recent years, the prevalence of carbapenem-resistant Pseudomonas aeruginosa isolates has become a worldwide concern. Rapid and accurate detection of carbapenemase-producing P. aeruginosa isolates is so important. The aim of this study was to evaluate the performance of the phenotypic methods such as Modified Hodge test (MHT), CarbaNP (CNPt), combined double-disk synergy test (CDDT), and carbapenem inactivation method (CIM) for rapid and accurate detection of clinical carbapenemase production of P. aeruginosa isolates. This study was performed on 97 P. aeruginosa strains, which were isolated from clinical samples in Hamadan hospitals, western Iran in 2017-2018. Antibiotic susceptibility testing was performed using disk diffusion and minimum inhibitory concentration (MIC) by E-test method. We evaluated the performance of MHT, CarbaNP, CDDT, and CIM tests in comparison to polymerase chain reaction (PCR) for the detection of carbapenemase-producing isolates. Additionally, the presence of carbapenem-resistant genes was investigated using the PCR method. Our findings showed that the highest resistance was to cefoxitin (94.8%). Moreover, among the carbapenem antibiotics, the highest resistance was to imipenem (49.4%). Among the 49 carbapenem-resistant isolates, 42 (85.7%) isolates were MIC positive. The results of phenotypic tests showed that CarbaNP, CIM, CDDT, and MHT tests were positive in (48/49, 97.95%), (46/49, 93.87%), (27/49, 57.44%), and (25/49, 53.19%) of isolates, respectively. CarbaNP and CIM tests showed high sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) compared to PCR in P. aeruginosa isolates. CarbaNP and CIM tests are highly sensitive and specific tests for identifying carbapenemase-producing P. aeruginosa isolates.

Monkeypox virus (MPXV), which belongs to the orthopoxvirus genus, causes zoonotic viral disease. This review discusses the biology, epidemiology, and evolution of MPXV infection, particularly cellular, human, and viral factors, virus transmission dynamics, infection, and persistence in nature. This review also describes the role of recombination, gene loss, and gene gain in MPXV evol-vement and the role of signal transduction in MPXV infection and provides an overview of the current access to therapeutic options for the treatment and prevention of MPXV. Finally, this review highlighted gaps in knowledge and proposed future research endeavors to address the unresolved questions.

Background and Objective: Due to the increased prevalence of antibiotic resistance to beta-lactam and carbapenem compounds, the identification of beta-lactamase-producing enzymes is essential for the timely treatment of such isolates. In this regard, the present study aimed to determine the prevalence of metallo-β-lactamases and Klebsiella pneumonia carbapenemase genes among the clinical isolates of Pseudomonas aeruginosa (P. aeruginosa). Materials and Methods: In this cross-sectional descriptive study, a total of 97 clinical isolates were collected from the hospitalized patients of Hamadan hospitals, Hamadan, Iran, within November 2017 to May 2018. After the confirmation of the isolated strains, antibiotic susceptibility of the isolates was determined by disk diffusion agar. Minimum inhibitory concentration (MIC) was performed for imipenem using the Etest method, Combined Double-Disk Test (CDDT), and Modified Hodge test (MHT). In addition, the identification of carbapenemase genes was conducted by polymerase chain reaction (PCR). Results: The obtained results of statistical analysis showed that the highest antibiotic resistance was reported to cefoxitin for 92 (94.8%) isolates, and the lowest antibiotic resistance was observed to piperacillin-tazobactam in 38 (39.2%) isolates. Among the carbapenem antibiotics, the highest antibiotic resistance was reported to imipenem for 48 (49.4%) isolates. Out of 49 (50.51%) carbapenem-resistant isolates, 42 (85.71%) isolates had positive results for MIC. Moreover, 26 (53.06%) and 25 (51.02%) isolates had positive results for IMP/EDTA (CDDT) and MHT test, respectively. The findings of PCR also showed that the highest and lowest gene presence among resistant isolates was related to IMP 20 (40.8%) and GIM gene 6 (12.24%), respectively. Conclusion: The obtained results of the present study showed that a high percentage of the assessed P. aeruginosa isolates were resistant to carbapenem antibiotics, and a high percentage of carbapenem-resistant isolates produced beta-lactamase genes.

Background: Nowadays, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains has dramatically restricted the treatment options against this microorganism. Therefore, in this study, we aimed to discover new drug targets and inhibitors against S. aureus. Methods: This study consists of two major sections. In the upstream evaluation, after a comprehensive core-proteome analysis, essential cytoplasmic proteins with no similarity to the human proteome were selected. Then the S. aureus metabolome-specific proteins were selected, and novel drug targets were identified using the DrugBank database. In the downstream analysis, a structure-based virtual screening approach was performed to reveal potential hit compounds against adenine N1 (m1A22)-tRNA methyltransferase (TrmK) using the StreptomeDB library and AutoDock Vina software. The compounds with a binding affinity > -9 kcal/mol were analyzed based on ADMET properties. Finally, the hit compounds were selected based on Lipinski’s rule of five (RO5). Results: Three proteins, including glycine glycosyltransferase (FemA), TrmK, and heptaprenyl pyrophosphate synthase subunit A (HepS1), were selected as feasible and promising drug targets based on PDB file availability and their essential role in the survival of the S. aureus. Finally, seven hit compounds, including Nocardioazine_A, Geninthiocin_D, Citreamicin_delta, Quinaldopeptin, Rachelmycin, Di-AFN_A1 and Naphthomycin_K were introduced against the binding cavity of TrmK, as a feasible drug target. Conclusion: The results of this study provided three feasible drug targets against S. aureus. In the following, seven hit compounds were introduced as potential inhibitors of TrmK, and Geninthiocin_D was identified as the most desirable agent. However, in vivo and in vitro investigations are needed to confirm the inhibitory effect of these agents on S. areus.