Apart from toxins, bacteria use specialized secretion systems to secrete many other effector proteins that interact with host cells. Gram-negative bacteria have a general secretion system and several classes of accessory secretion systems (types I–VI). A subset of these accessory secretion systems, called contact-dependent secretion systems, is present in many bacteria that contact or live inside host cells. The type III secretion system (Figure 23–7), for example, injects into the host-cell cytoplasm effector proteins that can elicit a variety of host cell responses that enable the bacterium to invade or survive. There is a remarkable degree of structural similarity between the type III syringe and the base of a bacterial flagellum. Because flagella are found in a wider range of bacteria than are type III secretion systems, and the secretion systems appear to be adaptations specific for pathogenesis, it seems likely that the type III secretion systems evolved from flagella. Other types of delivery systems used by bacterial pathogens appear to have evolved independently. For example, type IV secretion systems are closely related to the conjugation apparatus that many bacteria use to exchange genetic material.
Pathogenic fungi and protozoan parasites are eukaryotes, as are their hosts. Consequently, antifungal and antiparasitic drugs are often less effective and more toxic to the host than are antibiotics that target bacteria. A second characteristic of fungal and parasitic infections that makes them difficult to treat is the tendency of the pathogens to switch among several different forms during their life cycles. A drug that is effective at killing one form can be ineffective at killing another form; therefore the population can survive the treatment.
Fungi include both unicellular yeasts (such as Saccharomyces cerevisiae and Schizosaccharomyces pombe, which are used to bake bread and brew beer, and as model organisms for cell biology research) and filamentous, multicellular molds (like those found on moldy fruit or bread). Most of the important pathogenic fungi exhibit dimorphism—the ability to grow in either yeast or mold form. The yeast-to-mold or mold-to-yeast transition is frequently associated with infection.
Figure 23–7 Type III secretion systems that can deliver effector proteins into the cytosol of a host cell. (A) Electron micrograph of purified type III secretion systems, each of which consists of over two dozen proteins. (B) The large lower ring is embedded in the bacterial inner membrane, and the smaller upper ring is embedded in the bacterial outer membrane. During infection, docking of the tip of the hollow needle at a host-cell plasma membrane results in the secretion of bacterial translocator proteins (green), which form a pore in the host membrane, through which bacterial effector proteins are then secreted into the host cell.  (A, from O. Schraidt et al., PLoS Pathog. 6(4):e1000824, 2010.) in the environment in the host
Histoplasma capsulatum, for example, grows as a mold at low temperature in the soil, but it switches to a yeast form when inhaled into the lung, where it can cause the disease histoplasmosis (Figure 23–8).
Protozoan parasites are single-celled eukaryotes with more elaborate life cycles than fungi, and they frequently require more than one host. Malaria is the most devastating protozoal disease, infecting more than 200 million people every year and killing upward of 500,000. It is caused by four species of Plasmodium, which are transmitted to humans by the bite of the female Anopheles mosquito.
release of infection of red blood cells invasion of gut and growth