Inactivation of the Pta-AckA Pathway Causes Cell Death in Staphylococcus aureus

Authors

Marat R. Sadykov, University of Nebraska Medical Center
Vinai C. Thomas, University of Nebraska Medical Center
Darrell D. Marshall, University of Nebraska-Lincoln
Christopher J. Wenstrom, University of Nebraska Medical Center
Derek E. Moormeier, University of Nebraska Medical Center
Todd J. Widhelm, University of Nebraska Medical Center
Austin S. Nuxoll, University of Nebraska Medical Center
Robert Powers, University of Nebraska-LincolnFollow
Kenneth W. Bayles, University of Nebraska Medical CenterFollow

ORCID IDs

Kenneth W. Bayles

Date of this Version

2013

Citation

doi:10.1128/JB.00042-13

Comments

Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Abstract

During growth under conditions of glucose and oxygen excess, Staphylococcus aureus predominantly accumulates acetate in the culture medium, suggesting that the phosphotransacetylase-acetate kinase (Pta-AckA) pathway plays a crucial role in bacterial fitness. Previous studies demonstrated that these conditions also induce the S. aureus CidR regulon involved in the control of cell death. Interestingly, the CidR regulon is comprised of only two operons, both encoding pyruvate catabolic enzymes, suggesting an intimate relationship between pyruvate metabolism and cell death. To examine this relationship, we introduced ackA and pta mutations in S. aureus and tested their effects on bacterial growth, carbon and energy metabolism, cid expression, and cell death. Inactivation of the Pta-AckA pathway showed a drastic inhibitory effect on growth and caused accumulation of dead cells in both pta and ackA mutants. Surprisingly, inactivation of the Pta-AckA pathway did not lead to a decrease in the energy status of bacteria, as the intracellular concentrations of ATP, NAD⁺, and NADH were higher in the mutants. However, inactivation of this pathway increased the rate of glucose consumption, led to a metabolic block at the pyruvate node, and enhanced carbon flux through both glycolysis and the tricarboxylic acid (TCA) cycle. Intriguingly, disruption of the Pta-AckA pathway also induced the CidR regulon, suggesting that activation of alternative pyruvate catabolic pathways could be an important survival strategy for the mutants. Collectively, the results of this study demonstrate the indispensable role of the Pta-AckA pathway in S. aureus for maintaining energy and metabolic homeostasis during overflow metabolism.