The Role of Two-Component Signal Transduction Systems in Staphylococcus aureus Virulence Regulation

Abstract

Staphylococcus aureus is a versatile, opportunistic human pathogen that can asymptomatically colonize a human host but can also cause a variety of cutaneous and systemic infections. The ability of S. aureus to adapt to such diverse environments is reflected in the presence of complex regulatory networks fine-tuning metabolic and virulence gene expression. One of the most widely distributed mechanisms is the two-component signal transduction system (TCS) which allows a pathogen to alter its gene expression profile in response to environmental stimuli. The simpler TCSs consist of only a transmembrane histidine kinase (HK) and a cytosolic response regulator. S. aureus encodes a total of 16 conserved pairs of TCSs that are involved in diverse signalling cascades ranging from global virulence gene regulation (e.g. quorum sensing by the Agr system), the bacterial response to antimicrobial agents, cell wall metabolism, respiration and nutrient sensing. These regulatory circuits are often interconnected and affect each other's expression, thus fine-tuning staphylococcal gene regulation. This manuscript gives an overview of the current knowledge of staphylococcal environmental sensing by TCS and its influence on virulence gene expression and virulence itself. Understanding bacterial gene regulation by TCS can give major insights into staphylococcal pathogenicity and has important implications for knowledge-based drug design and vaccine formulation.

Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens

“…As happened with LysR-type regulators, many works relate the function of twocomponent systems to the control of pathogenesis in bacteria (278), but apart from the works cited in this section, no additional relatedness to PGN metabolism and/or ␤-lactamase regulation has been reported. This is the contrary to what happens with Gram-positive bacteria, where the volume of information on the topic is very important (279).…”

Dependence of the Staphylococcal Volatilome Composition on Microbial Nutrition

“…In vitro cultivation of staphylococci is fundamental to both clinical and research microbiology, and the selection of growth medium substantially influences staph growth rates, genetic integrity, pathogenicity, and metabolic capacity [ 1 , 2 , 3 , 4 , 5 ]. Depending on the species, staphylococci possess remarkable genetic plasticity, regulated by two-component systems that enable rapid responses to fluctuations in environmental conditions [ 1 , 4 , 6 ]. Additionally, staph is able to survive under host sequestration (also known as nutritional immunity) and microbial competition, both of which influence the availability of essential nutrients and carbon sources [ 1 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

The Staphylococcus aureus ArlRS two‐component system regulates virulence factor expression through MgrA

“…These virulence factors include secreted toxins and enzymes (Tam and Torres, ), cell wall‐anchored adhesins (Foster et al , ) and a variety of proteins involved in immune evasion (Thammavongsa et al , ). Expression of many of these virulence genes is controlled by two‐component systems (TCS) (Haag and Bagnoli, ) such as the agr quorum‐sensing system (Thoendel et al , ), as well as SaeRS (Liu et al , ), SrrAB (Yarwood et al , ) and ArlRS (Liang et al , ). These TCSs allow S. aureus to sense extracellular conditions and change gene expression accordingly.…”