The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake in Streptococcus mutans.

Sang-Joon Ahn,Kelly C Rice,Shailja Desai,Min Lin

doi:10.3390/microorganisms8060846

Sang-Joon Ahn, Kelly C Rice + Show 2 more

Open Access

https://doi.org/10.3390/microorganisms8060846

Copy DOI

Journal: Microorganisms	Publication Date: Jun 4, 2020
Citations: 2	License type: CC BY 4.0

Affiliation: University of Florida, Florida State University

Abstract

Pyruvate forms the central node of carbon metabolism and promotes growth as an alternative carbon source during starvation. We recently revealed that LrgAB functions as a stationary phase pyruvate uptake system in Streptococcus mutans, the primary causative agent of human dental caries, but its underlying regulatory mechanisms are still not clearly understood. This study was aimed at further characterizing the regulation of LrgAB from a metabolomic perspective. We utilized a series of GFP quantification, growth kinetics, and biochemical assays. We disclosed that LrgAB is critical for pyruvate uptake especially during growth under low-glucose stress. Inactivation of the Pta-Ack pathway, responsible for the conversion of acetyl-CoA to acetate, completely inhibits stationary phase lrgAB induction and pyruvate uptake, and renders cells insensitive to external pyruvate as a signal. Inactivation of Pfl, responsible for the conversion of pyruvate to acetyl-CoA under anaerobic conditions, also affected stationary phase pyruvate uptake. This study explores the metabolic components of pyruvate uptake regulation through LrgAB, and highlights its potential as a metabolic stimulator, contributing to the resuscitation and survival of S. mutans cells during nutritional stress.

Highlights

Streptococcus mutans, a primary contributor to human dental caries, is able to efficiently and rapidly adjust to carbohydrate limitation, which is essential for its pathogenic lifestyle, forming biofilms [1,2,3,4]
We recently revealed that the S. mutans LrgAB system—which is directly and positively regulated by the LytST two-component system (TCS) [28,29] and hypothesized to induce cell death and lysis with its partner operon CidAB—functions as a stationary phase pyruvate uptake system, with its activity modulated in response to glucose and oxygen levels [26]
We demonstrated that stationary phase lrgAB induction and pyruvate uptake are completely blocked in TV11, suggesting that TV medium provides a different environment from FMC

Summary

Introduction

Streptococcus mutans, a primary contributor to human dental caries, is able to efficiently and rapidly adjust to carbohydrate limitation, which is essential for its pathogenic lifestyle, forming biofilms [1,2,3,4] To cope with such an adverse environment, subpopulations of cells within the biofilm could enter low levels of metabolic phase [5,6,7,8] or undergo lysis or death [9,10] as strategies to survive and persist at a community level. From a metabolic standpoint, the regulation of LrgAB and pyruvate uptake is still not clearly understood

Objectives

Methods

Findings

Conclusion