Invasiveness and intracellular infection

Microorganisms that establish infections in humans do so by a number of means. For example, some bacteria remain associated with the surface of host cells, but elaborate a coating that provides protection from host immune defenses and external antimicrobial agents, such as antibiotics . Another strategy that is used by a number of disease-causing bacteria, virtually all viruses , single-celled eukaryotic parasites , and protozoa is the invasion of the host cells to which the microorganisms adhere. Once inside the host cell, the invading microbe is shielded from host defenses and therapeutic antimicrobial compounds.

Following the invasion of host cells, the microorganisms can establish an infection inside the host cells. This is referred to as intracellular infection. Once again, by remaining inside the host, the bacteria or protozoa are shielded from attack.

Intracellular infection presents a problem for the host, since the infection cannot be dealt with without damage to the host's own tissue. Many disease-causing microorganisms have adopted this mode of infection, including all viruses, some protozoa, and some bacteria. Indeed, some of these intracellular parasites depend absolutely on this mode of growth and cannot survive outside of the host cells. Two examples are the bacteria Chlamydia and Rickettsia. These bacteria are transmitted to another host only by direct contact of host cells, such as in sexual activity, or when they are sucked up by a biting insect and subsequently expelled into another host.

The molecular nature of invasiveness has been well studied in a number of Gram-negative bacteria. One example is designated as enteropathogenic Escherichia coli , or EPEC. This bacterium causes a severe, debilitating, and sometimes life-threatening diarrhea in infants, particularly in underdeveloped countries. EPEC associates with host epithelial cells in the intestinal tract by means of appendages known as fimbriae. Once adhesion is established, the bacterium produces a number of proteins that are then passed across the cell wall to the surface. Studies with mutants that do not manufacture one or more of these proteins have shown that the proteins are essential for invasion of the host cell. The exact function of these proteins in the invasive process is still unclear. But current data indicates that they have a role in altering the processes by which host cells transport compounds, and so may facilitate the movement of bacterial disease-causing compounds into the host cell. Finally, the bacteria form a protein that functions as an anchor, to irreversibly bind the bacterial cell to the host cell. Thus, while EPEC are not fully taken into the host cell, an intracellular invasion pathway is established.

A bona fide invasion of host cells is accomplished by the bacterium Salmonella. The bacteria have a number of genes, which are clustered together on the bacterial genome, which are activated following association of a bacterium with a host intestinal epithelial cell. The products of the genes operate in a similar fashion as those of EPEC. That is, they provide a conduit for the transport of bacterial compounds into the host cell. Salmonella additionally produces a protein that enters the host cell and modifies a scaffolding system in the cell that is called the actin cytoskeleton. The alteration is thought to cause the host cell membrane to become more pliable and capable of becoming much more wavy. This so-called ruffling can entrap a bacterium, enabling it to be taken into the host cell in a membrane-bound bag that is called a vacuole. Once inside the host, other proteins produced by the bacterium cause cell damage and allow the establishment of an infection. The bacteria remain inside the vacuole

Another Gram-negative species called Shigella flexneri also promotes the ruffling of the host membrane, which results in the uptake of the bacteria into the host cell. In contrast to Salmonella, Shigella flexneri break out of the vacuole and produce more copies of themselves in the cellular fluid of the host cell. In the host fluid a bacterium becomes coated with host molecules called actin. By propelling itself against the end of a host cell, a bacterium is able to use the stiff actin filament as a kind of battering ram, to punch a hole through to the neighbouring host cell. This enables the bacterial infection to spread from cell to cell without ever contact the surface of the host cells.

Other host cells can be invaded. For example, another Gram-negative bacterial species called Legionella pneumophila invades macrophages. Macrophages are white blood cells that are part of the immune system . By invading a macrophage, the bacteria can render the macrophage incapable of functioning in defending the body from infection. Thus, invasion serves not only to provide the bacteria with a safe haven for replication, but also compromises the immune system, facilitating the establishment of a bacterial infection.

Invasion of host cells and replication inside the cells can be a stage in the infectious cycle of microorganisms. For example, the single-celled eukaryotic parasites called Entamoeba histolytica and Entamoeba dispar can invade epithelial cells in the colon. Following the intracellular invasion the amoeba can become dispersed throughout the body via the bloodstream, leading to persistent infections, such as in the liver.

The protozoan called Cryptosporidium parvum causes a debilitating diarrhea, typically after being ingested in fecescontaminated drinking water. A key feature of the protozoan infection is the invasion of host epithelial cells in the ileum by a specialized form of the protozoan known as the sporozoite. Replication occurs inside the host cell with the progeny protozoa being released upon rupture of the host cell. The progeny can then go on to invade adjacent host tissue.

The wide spread distribution of host cell invasion and intracellular replication among microorganisms is indicative of the success of the strategy.

See also Bacteria and bacterial infection