Abstract
The Tol/Pal system (also written as “The Tol-Pal system”) is a set of protein complexes produced by most Gram-negative bacteria. It comprises the inner membrane-associated and the outer membrane-anchored subunits composed of the TolA, TolQ, and TolR proteins and the TolB and Pal proteins, respectively. Although the Tol/Pal system was first defined as bacterial proteins involved in colicin uptake of Escherichia coli, its global roles have been characterized in several studies as mentioned in this article. Pathogenesis of many Gram-negative pathogens is sustained by the Tol/Pal system. It is also essential for cell growth and fitness in some pathogens. Therefore, the Tol/Pal system is proposed as a potential target for antimicrobial chemotherapy. Although the tol/pal mutants are low in virulence, they still have the ability to stimulate the immune system. The Pal protein is highly immunogenic and induces both adaptive and innate immune responses. Therefore, the tol/pal mutant strains and Pal proteins also have potential vaccine properties. For these reasons, the Tol/Pal system represents a promising research target in the development of antibacterial therapeutic strategies for refractory infections caused by multi-drug-resistant (MDR), Gram-negative pathogens. In this paper, we summarize studies on the Tol/Pal system associated with bacterial pathogenesis and vaccine development.
Highlights
Antimicrobial agents are commonly used for the prevention and treatment of bacterial infections; an increasing number of bacteria have acquired resistance to conventional drugs
The Tol/Pal system brings about optimal virulence in many Gram-negative pathogens, while it is required for bacterial growth and survival in some species
The Tol/Pal system is an effective novel antibacterial target, that is distinguished from conventional targets, such as cell wall synthases, ribosomes, RNA polymerase and primary metabolic enzymes
Summary
Antimicrobial agents are commonly used for the prevention and treatment of bacterial infections; an increasing number of bacteria have acquired resistance to conventional drugs. Most Gram-negative bacteria are innately tolerant to some classes of antimicrobial agents [2,3]. They are hard to treat when additional resistance is acquired. Many classes of antimicrobial agents have been used in medical and industrial applications to prevent and treat infectious diseases caused by these pathogens, and their widespread application has resulted in the development of drug-resistant bacteria. There is increasing evidence that the Tol/Pal system is required for virulence in many species of Gram-negative bacteria, and cell growth in some species. We discuss the potential of Tol/Pal proteins in drug and vaccine development. Bacterial invasion and growth in epithelial cells, Innate tolerance to antibiotics, bile acid and human complement
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