Protein secretion and the pathogenesis of bacterial infections

Instruments of bacterial warfare

The skin, the oral cavity, and the gastrointestinal tract of humans are colonized with bacteria. Microbial entry into the blood or blood-circulated tissues is hindered by anatomical barriers. The barriers consist of epithelia as well as membranes that are fortified by layers of collagen and other connective tissues. Following the breakdown of a barrier, the dwindling of an immune system, or an attack by particularly virulent bacteria, microbes gain entry into deeper tissues and multiply within newly conquered space. Human disease is the result of such bacterial multiplication. Microbial entry into circulated tissue is accompanied by an immune response. Immune cells recognize bacterial products (lipids, carbohydrates, peptidoglycan, or protein decorations) and respond by attracting macrophages, polymorph-nuclear leukocytes, or other immune cells in an effort to kill the invading pathogen (Medzhitov and Janeway 1999; Aderem and Ulevitch 2000). Many bacterial pathogens have evolved to enter and multiply within blood-circulated tissues (Finlay and Falkow 1997). The underlying pathogenic strategies are remarkably diverse and often result in unique disease symptoms. Nevertheless, all mechanisms of bacterial manipulation of the host organisms can be viewed in three principal categories: microbial adhesion, secretion of toxins into the extracellular milieu, and injection of virulence factors into host cells. There are three rules of thumb that bacterial pathogens must consider if they want to mount a successful infection.

If you want to invade a host—stick to it

Vibrio cholerae adhere to human intestinal tissues and secrete a toxin that, once engulfed by epithelial cells, causes a fulminant diarrhea. Mutants lacking theVibrio surface adhesin (TCP pili) cannot stick to the intestines and fail to cause disease (Herrington et al. 1988). Microbial adhesion to host tissues can be mediated by individual proteins or by sophisticated organelles such as pili. Pili form fibrous structures that emanate from the bacterial surface and display an adhesive property at the tip. …