RT Journal Article
SR Electronic
T1 IlvY is an important regulator of <em>Shigella</em> infection <em>in vitro</em> and <em>in vivo</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.28.220327
DO 10.1101/2020.07.28.220327
A1 Mayumi K. Holly
A1 Mark C. Anderson
A1 Lesley M. Rabago
A1 Azadeh Saffarian
A1 Benoit S. Marteyn
A1 Samuel L.M. Arnold
YR 2020
UL http://biorxiv.org/content/early/2020/07/28/2020.07.28.220327.abstract
AB Shigellosis results from oral ingestion of the Gram-negative bacteria Shigella, and symptoms include severe diarrhea and dysentery. In the absence of vaccines, small molecule antibacterial drugs have provided treatment options for shigellosis. However, Shigella drug resistance is rapidly emerging, and Shigella strains with resistance to both third-generation cephalosporins and azithromycin have been identified in Asia. A re-conceptualization is needed regarding the development of therapeutics that target bacterial pathogens in order to reduce resistance development and alteration of gut microbiota, which is depleted upon treatment with wide spectrum antibiotics, thereby increasing susceptibility to subsequent enteric infections. A more organism-specific approach is to develop agents targeting virulence factors such as toxins, adhesins, invasins, quorum sensing, and protein secretion systems. For Shigella, there is interest in targeting transcription factors essential for Shigella infection in vivo rather than specific effectors. Here we describe the importance of the Shigella transcription factor IlvY in Shigella virulence in vitro and in vivo. This work included the development of a novel, oral mouse model of Shigella infection with wild-type adult mice. Unlike previous models, mice do not require antibiotic pretreatment or diet modifications. This mouse model was used to demonstrate the importance of IlvY for Shigella in vivo survival and that deletion of ilvY impacts host responses to infection. These results illustrate that IlvY is a potential therapeutic target for the treatment of shigellosis. In addition, the novel mouse model provides an exciting new opportunity to investigate therapeutic efficacy against Shigella infection and host responses to infection.Competing Interest StatementThe authors have declared no competing interest.