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Saranathan, R. and Sudhakar, P. and Sawant, A.R. and Tomar, A. and Madhangi, M. and Sah, S. and Annapurna, S. and Arunkumar, K.P. and Prashanth, K. (2017) Disruption of tetR type regulator adeN by mobile genetic element confers elevated virulence in Acinetobacter baumannii. Virulence, 8 (7). pp. 1316-1334. ISSN 2150-5594

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Abstract

Acinetobacter baumannii is an important human pathogen and considered as a major threat due to its extreme drug resistance. In this study, the genome of a hyper-virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was sequenced and analysed to understand its mechanisms of virulence, resistance and evolution. Comparative genomics analysis of PKAB07 revealed virulence and resistance related genes scattered throughout the genome, instead of being organized as an island, indicating the highly mosaic nature of the genome. Many intermittent horizontal gene transfer events, insertion sequence (IS) element insertions identified were augmenting resistance machinery and elevating the SNP densities in A. baumannii eventually aiding in their swift evolution. ISAba1, the most widely distributed insertion sequence in A. baumannii was found in multiple sites in PKAB07. Out of many ISAba1 insertions, we identified novel insertions in nine different genes wherein insertional inactivation of adeN (tetR type regulator) was significant. To assess the significance of this disruption in A. baumannii, adeN mutant and complement strains were constructed in A. baumannii ATCC 17978 strain and studied. Biofilm levels were abrogated in the adeN knock-out when compared to the wild type and complemented strain of adeN knock-out. Virulence of the adeN knock-out mutant strain was observed to be high, which was validated by in vitro experiments and Galleria mellonella infection model. The over-expression of adeJ, a major component of AdeIJK efflux pump observed in adeN knockout strain could be the possible reason for the elevated virulence in adeN mutant and PKB07 strain. Knocking out of adeN in ATCC strain led to increased resistance and virulence at par with the PKAB07.Disruption of tetR type regulator adeN by ISAba1 consequently has led to elevated virulence in this pathogen.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 27 Apr 2017 11:15
Last Modified: 27 Dec 2018 19:43
URI: http://cdfd.sciencecentral.in/id/eprint/776

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