Increased Extracellular ATP: An Omen of Bacterial RTX Toxin-Induced Hemolysis?

Bacterial infection is a major threat to human health. Although pathogenic bacteria vary in their virulence, it has been recognized that many pathogenic bacteria share common mechanisms when attacking host cells and tissues. Some pathogenic bacteria synthesize and secrete polysaccharides to form an extracellular capsule. Capsules serve as virulence determinants by multiple mechanisms including facilitation of bacterial adherence, evasion of the immune response, and antibiotic resistance [1]. Moreover, to the exterior of bacterial plasma membranes are certain toxic components (e.g., lipopolysaccharide (LPS) in Gram-negative bacteria, and peptidoglycan fragments and teichoic acids in Gram-positive bacteria) that play key roles in causing bacterial septic shock or multiple organ dysfunction [2]. Significantly, bacteria may secrete proteinaceous or non-proteinaceous molecules, namely exotoxins, capable of directly destroying host cells. The Repeat-in-Toxin (RTX) family is a group of virulence-associated exotoxins that are generated by Gram-negative bacteria and are noted for their ability to form pores on the membrane of host cells including leukocytes [3]. Despite the intense effort that has been input into investigating the interaction between RTX toxins and host cells during bacterial infection, our understanding of how RTX toxins insert into host cell membranes, and in turn, how host cells respond to the challenge of these toxins remains very limited. α-Hemolysin (Hly A) and leukotoxin A (Ltx A) are two typical RTX toxins that are secreted by bacteria E. coli and Aggregatibacter actinomycetem, respectively. Exposure of blood cells such as erythrocytes to these toxins may damage the integrity of cell membranes and eventually lead to cell OPEN ACCESS