Functional characterization of novel and putative two component systems in Acinetobacter baumannii

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Date
2022-04-21
Authors
Thakur, Debjyoti
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Abstract
Acinetobacter baumannii is a pathogenic bacterium responsible for various hospital-acquired infections in immunocompromised patients. It is highly resilient and can survive in harsh environmental conditions. A. baumannii is infamous for its ability to develop resistance against various antimicrobials. Two Component Systems (TCS) are signal transduction systems which enable bacteria to sense and adapt to changes in environmental conditions. Various studies have indicated their involvement in regulation of antibiotic susceptibility and virulence mechanisms in bacteria. In this project, we investigated the functional characteristics of novel and putative TCSs in A. baumannii and their role in regulation of antibiotic susceptibility and virulence phenotypes. The first part of this study involved the functional characterization of AvnR, a conserved response regulator, in the clinical isolate - A. baumannii AB030. AvnR has previously been linked with regulation of various virulence-associated phenotypes including biofilm formation, motility, and nitrogen metabolism. The avnR gene in A. baumannii AB030 has been found to be naturally disrupted by an insertion sequence, rendering it non-functional. We investigated the impact of this disruption on biofilm formation, motility, and nitrogen metabolism in AB030. Complementation of avnR in AB030 had no effect on biofilm formation and motility phenotypes; however, changes in its nitrogen metabolism profile was observed. Complement strain, AB030:mini-Tn7:avnR, exhibited enhanced growth in L-serine and L-arginine compared to the wild type, whereas a decrease in growth was observed in Alanine-Histidine, Alanine-Leucine, and L-Valine. In the second part of this study, the functional characteristics of a putative TCS, A1S_1977-78, was investigated in A. baumannii ATCC 17978. Previous studies have indicated a potential link between this TCS and regulation of AdeN, a Tet-R type regulator protein. AdeN is associated with expression of AdeIJK efflux pump as well as virulence-associated phenotypes. A1S_1977-78 was, therefore, predicted to be associated with antibiotic susceptibility and virulence in A. baumannii. Deletion of A1S_1977-78 in ATCC 17978 genome resulted in a two-fold increase in susceptibility to ciprofloxacin. However, no change in expression was observed for adeN and adeIJK in the deletion mutant compared to the wild type strain, suggesting that A1S_1977-78 may not be involved in regulation of adeN/adeIJK expression.
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Keywords
Two Component Systems, AvnR, Antibiotics, Antibiotic resistance, Acinetobacter baumannii, AB030, A1S_1977, A1S_1978
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