Enterococcus faecalis reconfigures its transcriptional regulatory network activation at different copper levels

Abstract

A gene regulatory network was generated in the bacterium Enterococcus faecalis in order to understand how this organism can activate its expression under different copper concentrations. The topological evaluation of the network showed common patterns described in other organisms. Integrating microarray experiments allowed the identification of sub-networks activated under low (0.05 mM CuSO4) and high (0.5 mM CuSO4) copper concentrations. The analysis indicates the presence of specific functionally activated modules induced by copper, highlighting the regulons LysR, ArgR as global regulators and CopY, Fur and LexA as local regulators. Taking advantage of the fact that E. faecalis presented a homeostatic module isolated, we produced an in vivo intervention removing this system from the cell without affecting the connectivity of the global transcriptional network. This strategy led us to find that this bacterium can reconfigure its gene expression to maintain cellular homeostasis, activating new modules principally related to glucose metabolism and transcriptional processes. Finally, these results position E. faecalis as the organism having the most complete and controllable systemic model of copper homeostasis available to date.

Different Transcriptional Responses from Slow and Fast Growth Rate Strains of Listeria monocytogenes Adapted to Low Temperature

“…Microarray expression data show that L. monocytogenes under low temperature activates mechanisms involved in cold protection, and induces the expression of genes related to translation, transcription, cell division, basal metabolism, and energy production ( Garmyn et al, 2012 ; Rantsiou et al, 2012 ; Durack et al, 2013 ). These findings reveal that the adaptation to low temperature can be classified as a complex response ( Latorre et al, 2014 ), where the bacterium must adjust its transcriptional response at the system level in order to maintain cellular homeostasis.…”

Stress Physiology of Lactic Acid Bacteria

“…LexA regulons have been identified in some LAB species, such as Lb. plantarum (351) and E. faecalis (352). The uvrA gene, which encodes a nucleotide excision repair protein and is a typical member of LexA regulons, has been characterized for S. mutans (353) and Lb.…”

The Role of Fur in the Transcriptional and Iron Homeostatic Response of Enterococcus faecalis

“…In particular, the increase in zinc in the mutant strain exposed to iron excess can be explained as a requirement of this essential micronutrient as a cofactor in several oxidative stress enzymes and transcriptional factors. A similar phenotype occurs when the bacterium is exposed to other metals with redox activity ( Latorre et al, 2014 ).…”

“…A previous in silico strategy identified three putative transport systems involved in iron homeostasis controlled by Fur in E. faecalis , the operons fhuDCBG (ferrichrome transporter), feoAB (ferrous iron transport), and ycl QPN (iron compound ABC transporter) ( Latorre et al, 2014 ). To confirm if these three operons are direct targets of Fur, we generated a null deletion mutant of this protein (Δ fur ) in E. faecalis , to later determine the transcript abundance of the three iron uptake operons between the wild type and the mutant strain.…”