Acinetobacter baumannii toksino-antitoksino sistemos CheTA antitoksino veikimo mechanizmo paieška /

Investigation of Activity of Acinetobacter baumannii Toxin-antitoxin System Antitoxin Acinetobacter baumannii is a gram negative opportunistic pathogen which causes variety of nosocomial infections. Due to the ability to persist in clinical environment and rapidly acquire antibiotic resistant phenotype it has emerged as one of the most important human pathogens in hospital settings. Despite the increasing effort of researchers, molecular mechanisms which contribute to this successful emergence remain elusive. In the last two decades bacterial toxin-antitoxin (TA) systems, genetic loci abundant in low copy number plasmids and chromosomes, sparked a great interest from scientists. They have been proposed to fulfill a myriad of roles in bacterial physiology, including plasmid stabilization, stress response, persistence and protection from phage infections. A standard TA system is composed of a stable toxin and a labile antitoxin that neutralizes the toxic effect of its cognate toxin. Under stressful conditions such as nutrient starvation or exposure to antibiotics, antitoxin is rapidly degraded allowing toxin to obstruct essential cellular processes such as DNA replication, translation or peptidoglycan synthesis which subsequently cause growth arrest. In this work we examined a novel A. baumannii TA system CheTA, which exhibits unique organization, due to toxin possessing an HTH domain, more common for antitoxins of TA systems, and antitoxin possessing GNAT fold. By using kill-rescue assay we determined that the system is functional in both E. coli host and Acinetobacter baylyi strain. CheA protein structure prediction indicated several conservative amino acid positions, possibly important for acetyltransferase activity. When mutations were introduced in the proposed positions in GNAT acetyl-CoA binding pocket, they were not critical for neutralization of the toxin. This might indicate differences among GNAT protein active sites as well as toxin inactivation of this TA system being achieved by other means.

Grantor dc:publisher

Institutional Repository of Vilnius University

Year dc:date

2016

Author dc:creator

• Čepauskas, Albinas,

Contributors dc:contributor

• Armalytė, Julija

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

lit

Repository record dc:identifier

https://repository.vu.lt/VU:ELABAETD20217808&prefLang=en_US

OAI identifier oai:identifier

oai:vu.lt:elaba:20217808