Characterization of two component systems of Acinetobacter baumannii.

Acinetobacter baumannii is an important opportunistic pathogen of hospital acquired infection, particularly in intensive care units. The emergence and rapid spread of multidrug-resistant A. baumannii strains has become a major health threat worldwide which severely limits the treatment options for this pathogen. This work investigated global mechanisms of antibiotic resistance and virulence of the problematic pathogen A. baumannii, in particular those mediated by two component regulatory systems (TCSs), that typically consist of a membrane bound sensor kinase and a cognate response regulator. Bacterial TCSs play an important role in the regulation of adaptation to different environmental conditions. Five TCSs in A. baumannii have been characterized; however, there are a number of putative two component systems encoded in the genome of A. baumannii that await detailed characterization. Differential expressions of six different TCSs was observed in two clinical isolates of A. baumannii AB030 and AB031, and whole-genome sequencing of both clinical isolates was performed. Data obtained from the comparative whole-genome analysis revealed the presence of an insertion element in the orphan TCSs response regulator A1S_2006 in AB030, mutation in the promoter region and an 1189 DNA insertion element were present in AdeRS system in AB031. The whole-genome sequencing analysis of TCSs operons in AB030 and AB031 also identified sequence polymorphisms that could alter the activities of these TCSs in AB030 and AB031. Finally, we identified A1S_3229_30 an excellent candidate that may act as global regulator of antibiotic and virulence in A. baumannii. The sequence of A1S_3229_30 was highly conserved among the wild-type ATCC17978, AB030 and AB031, and showed 73% identity to the amgRS operon that encodes for the well characterized AmgRS system that confer resistance to aminoglycoside antibiotics and required for the virulence of the problematic pathogen P. aeruginosa