Investigation of the potential role of toxin-antitoxin systems in virulence and antimicrobial resistance in some gram-negative bacteria / Shahira Abdelsalam Elbanna ; Nayera Ahmed Moneib , Ramy Karam Aziz , Reham Samir Mohamed

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Microbiology and Immunology

Toxin-antitoxin (TA) systems are widespread among bacteria, archaea and fungi. They play different roles, such as postsegregational killing, abortive infection, and persister cell formation, and have recently been proposed as novel drug targets. TA systems are classified into six types (I-VI), based on the nature of antitoxin and its mode of action. This workaimed to screen the pathogen Acinetobacter baumannii, known for its alarming antimicrobial resistance, for TA systems, and to identify a CptBA-like Type IV TA, one of the least characterized systems. Comparative genomics demonstrated the distribution of E. coliCptBA-like systems among Gram-negative bacteria, while phylogenetic analysis of CptA and CptBdelineated two major groups, in each of which Acinetobacter spp. clustered together. Multiple sequence alignment indicated the conservation of cptA and cptB in 195 strains of A. baumannii in the same syntenic order. Using A. baumannii recombinant cptA and cptB, cloned under different promoters, confirmed thetoxin-antitoxin nature of their encoded proteins, as cptB expression was able to reverse growth inhibition by CptA in a dose-time-dependent manner.Furthermore, transcriptional analysis of cptBA in its natural bacterial host (A. baumannii) demonstrated that the cptBA locus is actively co-transcribed under normal conditions; yet, their transcriptional levels were reduced under oxidative and antibiotic stress, including ciprofloxacin and meropenem

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