Type

Journal Article

Authors

Kimon Andreas G. Karatzas
Conor P O'Byrne
Cormac G M Gahan
Colin Hill
Pat G. Casey
Aiden Finnerty
Conor Feehily

Subjects

Microbiology

Topics
gene glutamate decarboxylase oral infection listeria monocytogenes acid resistance survival acid functional genomics regulation expression inhibition virulence stress divergent evolution resistance

Divergent evolution of the activity and regulation of the glutamate decarboxylase systems in Listeria monocytogenes EGD-e and 10403S: roles in virulence and acid tolerance. (2014)

Abstract The glutamate decarboxylase (GAD) system has been shown to be important for the survival of Listeria monocytogenes in low pH environments. The bacterium can use this faculty to maintain pH homeostasis under acidic conditions. The accepted model for the GAD system proposes that the antiport of glutamate into the bacterial cell in exchange for γ-aminobutyric acid (GABA) is coupled to an intracellular decarboxylation reaction of glutamate into GABA that consumes protons and therefore facilitates pH homeostasis. Most strains of L. monocytogenes possess three decarboxylase genes (gadD1, D2 & D3) and two antiporter genes (gadT1 & gadT2). Here, we confirm that the gadD3 encodes a glutamate decarboxylase dedicated to the intracellular GAD system (GADi), which produces GABA from cytoplasmic glutamate in the absence of antiport activity. We also compare the functionality of the GAD system between two commonly studied reference strains, EGD-e and 10403S with differences in terms of acid resistance. Through functional genomics we show that EGD-e is unable to export GABA and relies exclusively in the GADi system, which is driven primarily by GadD3 in this strain. In contrast 10403S relies upon GadD2 to maintain both an intracellular and extracellular GAD system (GADi/GADe). Through experiments with a murinised variant of EGD-e (EGDm) in mice, we found that the GAD system plays a significant role in the overall virulence of this strain. Double mutants lacking either gadD1D3 or gadD2D3 of the GAD system displayed reduced acid tolerance and were significantly affected in their ability to cause infection following oral inoculation. Since EGDm exploits GADi but not GADe the results indicate that the GADi system makes a contribution to virulence within the mouse. Furthermore, we also provide evidence that there might be a separate line of evolution in the GAD system between two commonly used reference strains.
Collections Ireland -> University College Cork -> APC Microbiome Institute
Ireland -> University College Cork -> PubMed
Ireland -> University College Cork -> College of Science, Engineering and Food Science
Ireland -> University College Cork -> APC Microbiome Institute- Journal Articles
Ireland -> University College Cork -> Microbiology
Ireland -> University College Cork -> Research Institutes and Centres
Ireland -> University College Cork -> Microbiology - Journal Articles

Full list of authors on original publication

Kimon Andreas G. Karatzas, Conor P O'Byrne, Cormac G M Gahan, Colin Hill, Pat G. Casey, Aiden Finnerty, Conor Feehily

Experts in our system

1
Kimon Andreas G. Karatzas
National University of Ireland Galway
 
2
Cormac G M Gahan
University College Cork
Total Publications: 109
 
3
Colin Hill
University College Cork
Total Publications: 351
 
4
Pat G. Casey
University College Cork
Total Publications: 40
 
5
Conor Feehily
National University of Ireland Galway
Total Publications: 3