Faculty Collaboration Database

Nutritional control of antibiotic resistance via an interface between the phosphotransferase system and a two-component signaling system. Antimicrob Agents Chemother 2014;58(2):957-65

Date

11/28/2013

Pubmed ID

24277024

Pubmed Central ID

PMC3910890

DOI

10.1128/AAC.01919-13

Scopus ID

2-s2.0-84893482882 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

Enterococci are ubiquitous inhabitants of the gastrointestinal (GI) tract. However, antibiotic-resistant enterococci are also major causes of hospital-acquired infections. Enterococci are intrinsically resistant to cephalosporins, enabling growth to abnormally high densities in the GI tract in patients during cephalosporin therapy, thereby promoting dissemination to other sites where they cause infection. Despite its importance, many questions about the underlying basis for cephalosporin resistance remain. A specific two-component signaling system, composed of the CroS sensor kinase and its cognate response regulator (CroR), is required for cephalosporin resistance in Enterococcus faecalis, but little is known about the factors that control this signaling system to modulate resistance. To explore the signaling network in which CroR participates to influence cephalosporin resistance, we employed a protein fragment complementation assay to detect protein-protein interactions in E. faecalis cells, revealing a previously unknown association of CroR with the HPr protein of the phosphotransferase system (PTS) responsible for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses indicate that association with HPr restricts the ability of CroR to promote cephalosporin resistance and gene expression in a nutrient-dependent manner. Mutational analysis suggests that the interface used by HPr to associate with CroR is distinct from the interface used to associate with other cellular partners. Our results define a physical and functional connection between a critical nutrient-responsive signaling system (the PTS) and a two-component signaling system that drives antibiotic resistance in E. faecalis, and they suggest a general strategy by which bacteria can integrate their nutritional status with diverse environmental stimuli.

Author List

Snyder H, Kellogg SL, Skarda LM, Little JL, Kristich CJ

Author

Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anti-Bacterial Agents
Bacterial Proteins
Ceftriaxone
Cephalosporin Resistance
Culture Media
Enterococcus faecalis
Gene Expression
Genes, Reporter
Glucose
Lac Operon
Microbial Sensitivity Tests
Mutation
Phosphoenolpyruvate Sugar Phosphotransferase System
Protein Kinases
Signal Transduction