TYROSINE PROTEIN KINASE MODELING AND MOLECULAR CHARACTERIZATION OF SOME VIRULENCE FACTORS IN MULTIDRUG RESISTANT ACINETOBACTER BAUMANNII IN IRAQ

Abstract

Background: Hospital-acquired infections are often caused by multidrug-resistant Acinetobacter baumannii, an opportunistic bacterium. Resistance and multivirulence explain its clinical persistence. Objective: A.baumannii clinical isolates in Iraq will be evaluated for antibiotic resistance, biofilm formation, efflux pump activity, elastase, and phospholipase at phenotypic and molecular levels. Material and Methods: thirty A.baumannii isolates were characterized using standard biochemical assays and PCR primers specific to the species. The Vitek 2 compact system screened antibiotic susceptibility. The microtiter plate method was employed for biofilm growth and ethidium bromide for efflux pump activity screening. PCR was used to detect virulence and resistance genes ompA, adeB, LasB, plcN and PTK. Molecular modeling of the Tyrosine Protein Kinase (PTK) enzyme using homology modeling predicted its three-dimensional structure and assessed its therapeutic potential. Results: Thirty isolates of A.baumannii showed (100%) resistant to cefotaxime, 93%ciprofloxacin, (92%) ampicillin-sulbactam, (91%) amikacin, (89%) meropenem, (86%) cefepime, ceftazidime, imipenem and piperacillin tazobactam, (83%) gentamicin, (72%) trimethoprim-sulfamethoxazole, and (3%) colistin. Biofilm analysis showed that 29 (96%) isolates produced biofilm to varying degrees (weak, moderate, strong), and qualitative and quantitative results were similar. Phenotypically, 22 (73.3%) isolates had efflux pump activity. PCR demonstrated significant incidence of virulence genes ompA 29 (96.6%), adeB 27 (90%), LasB 17 (56%), plcN 20 (66.6%) and PTK 30(100%). Molecular modeling showed that PTK has a membrane domain and a spherical extracellular domain with helices and folded sheets, similar to the Wzc protein in E. coli, highlighting its potential as a therapeutic target. Conclusion: Drug resistant A. baumannii isolates with biofilm formation, efflux pumps and proteases are capable to survive and cause severe infection. PTK introduced as a well-defined hypothetical structure and a potential drug target for future therapeutic development.