The role of Gram-negative rods in induction/regulation of apoptosis

Apoptosis is a physiological, genetically controlled process. It plays an important role in ontogenesis, tissue renewal and in the elimination of cells with irreparable damage of genomic DNA. Apoptosis can be divided into three phases: initiation, effector phase and destruction. Programmed cell death is initiated through the intrinsic or extrinsic pathway. The effector phase involves the activation of caspases. During the third phase, called destruction, some characteristic features such as increase in membrane permeability, membrane blebbing, nuclear condensation and DNA fragmentation are observed. There is considerable evidence that Gram-negative bacteria have the ability to induce apoptosis in infected cells. Some bacterial pathogens can initiate apoptosis by activating receptors at the cell surface. Gram-negative bacteria produce toxins, which cause direct damage of the host cell membrane and permit the leakage of cellular components. Other bacterial toxins exhibit proapoptotic activity within the host cell. Apoptosis can be initiated by effector proteins delivered into the host cell cytosol by the type III secretion apparatus. Studies indicate that programmed cell death can be also activated by specific cell cycle modifications. Many apoptotic mechanisms are not fully understood. Further studies could provide necessary information which would help prevent and treat bacterial diseases.