Salmonella is a genus of bacteria responsible for many foodborne illnesses worldwide, a condition known as salmonellosis. These microorganisms are widespread in nature and can be transmitted from animals to humans, often through contaminated food products. The genus includes two main species, Salmonella enterica and Salmonella bongori, with S. enterica being further divided into numerous serotypes that are the primary cause of disease in humans.
The Salmonella Cell Structure
Salmonella is a rod-shaped, Gram-negative bacterium measuring between 2 to 5 micrometers in length. Its motility is facilitated by flagella, long appendages that cover the cell body, which act as propellers. This rotation allows the bacterium to move through environments like the intestinal mucus layer to reach host cells.
The bacterium’s surface also has shorter, hair-like structures known as pili or fimbriae. These appendages are for adhesion, enabling the cell to attach to host intestinal cells as a step for infection. Some specialized pili can also transfer genetic material between bacteria, contributing to the spread of traits like antibiotic resistance.
The cell envelope of Salmonella is characteristic of Gram-negative bacteria, consisting of an inner cytoplasmic membrane and an outer membrane, separated by a thin layer of peptidoglycan. A feature of the outer membrane is lipopolysaccharide (LPS), a molecule that acts as an endotoxin. The LPS structure is composed of an O-polysaccharide chain, a core polysaccharide, and an inner lipid A component. Within the cytoplasm lies the nucleoid, where the cell’s genetic material is located, along with ribosomes and often plasmids.
Mechanisms of Host Cell Invasion
Salmonella actively engineers its own entry into host cells, particularly the epithelial cells lining the intestine. The bacterium uses molecular machinery called a Type III Secretion System (T3SS) to manipulate the host. The T3SS acts like a molecular syringe, piercing the host cell membrane and injecting bacterial proteins, known as effector proteins, into the host cell’s cytoplasm.
Upon delivery, these effector proteins orchestrate a rearrangement of the host cell’s cytoskeleton. They target proteins that regulate actin, causing it to rapidly assemble and disassemble. This manipulation induces changes on the host cell surface, leading to the formation of large, wave-like protrusions called membrane ruffles.
These ruffles extend from the host cell and fold over the bacterium, engulfing it in a process that resembles a trigger mechanism. The cell membrane then closes around the bacterium, drawing it into the cell’s interior within a membrane-bound compartment. Recent studies have shown that Salmonella can co-opt existing reservoirs of host cell membrane to form these ruffles quickly, highlighting the efficiency of its invasion strategy.
Intracellular Life and Replication Strategies
Once inside the host cell, Salmonella is enclosed within a vesicle known as the Salmonella-Containing Vacuole (SCV). The bacterium’s challenge is to avoid destruction by the cell’s natural defense mechanisms. Normally, such vacuoles would fuse with lysosomes, which are organelles filled with digestive enzymes. Salmonella, however, actively modifies the SCV to prevent this fusion.
To survive and replicate, the bacterium employs a second Type III Secretion System (T3SS-2), which is distinct from the one used for invasion. This system secretes a different set of effector proteins from within the SCV into the host cell cytoplasm. These proteins further manipulate the host cell, helping to establish a protected niche where the bacterium can multiply. The SCV is transformed into a hospitable environment, providing the necessary nutrients for bacterial replication.
Within this protective vacuole, Salmonella begins to divide, increasing its numbers. The integrity of the SCV is maintained throughout this replication phase, shielding the bacteria from the host cell’s defenses. This intracellular lifestyle allows the pathogen to multiply undetected by the broader immune system for a period, establishing a strong foothold within the host tissue.
Cellular Factors Contributing to Disease
The lipopolysaccharide (LPS) molecule, a component of the outer membrane, functions as a potent endotoxin. When bacterial cells are broken down, LPS is released, triggering a strong inflammatory response from the host’s immune system. This response leads to symptoms like fever and tissue inflammation.
The effector proteins injected by the T3SS also play a role in causing disease. These proteins interfere with the normal functions of intestinal cells, disrupting ion channels and leading to a secretion of fluids and electrolytes into the intestinal lumen. This disruption is the primary cause of the diarrhea associated with salmonellosis. The inflammatory response initiated by both LPS and effector proteins contributes to damage of the intestinal lining.
The bacterium’s ability to replicate within the SCV and eventually spread from the initial infection site contributes to the persistence and severity of the disease. As bacteria multiply, they can cause the host cell to die, releasing the pathogens to infect neighboring cells. In some cases, Salmonella can gain access to the bloodstream and disseminate to other organs, leading to a more severe, systemic infection.