Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Isotypes and allotypes

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INVASIVENESS AND INTRACELLULAR

INFECTIONInvasiveness and intracellular infection

Microorganismsthat establish infections in humans do so by a

number of means. For example, some bacteriaremain associ-

ated 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 protozoais 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 intracellu-

lar parasites depend absolutely on this mode of growth and

cannot survive outside of the host cells. Two examples are the

bacteria Chlamydiaand Rickettsia. These bacteria are trans-

mitted 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 underdevel-

oped 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 num-

ber of proteins that are then passed across the cell wall to the

surface. Studies with mutantsthat do not manufacture one or

more of these proteins have shown that the proteins are essen-

tial 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 oper-

ate in a similar fashion as those of EPEC. That is, they provide

a conduit for the transport of bacterial compounds into the host

cell. Salmonellaadditionally 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 mem-

brane-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 flexneribreak out of the vacuole and pro-

duce more copies of themselves in the cellular fluid of the host

cell. In the host fluid a bacterium becomes coated with host mol-

ecules 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 infectionto 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 pneu-

mophilainvades macrophages. Macrophages are white blood

cells that are part of the immune system. By invading a

macrophage, the bacteria can render the macrophage inca-

pable 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 exam-

ple, the single-celled eukaryotic parasites called Entamoeba

histolyticaand Entamoeba disparcan 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 parvumcauses a

debilitating diarrhea, typically after being ingested in feces-

contaminated 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 proto-

zoa 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 alsoBacteria and bacterial infection

IIsotypes and allotypesSOTYPES AND ALLOTYPES

Isotype and allotype are terms that relate to the structure of a

component of the immune system that is called an

immunoglobulin.

Immunoglobulinsbind their corresponding antigen. An

immunoglobulin can be static, as part of a membrane-bound

receptor to which an antigen binds, or can be floating freely in

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