Type Three and Four Secretion Systems

• Type three and four secretion systems are complex structures used by typically gram-negative pathogens.
• These systems provide unique virulence mechanisms.
• They consist of complex proteins called translocators.
• Translocators move proteins, also known as effectors, that enable pathogens to colonize, multiply, and persist within a host.

Type Three Secretion System

• Consists of two rings, creating a continuous pathway across the inner and outer membranes, including the peptidoglycan layer.
• A needle-like structure connects to the host's outer membrane, projecting from the bacterial surface.
• E. coli uses this system with additional filaments to attach to the host.
• Effector proteins go through the hollow tube, changing the host cell and increasing the pathogen's virulence.
• Examples of bacteria using this system include Shigella, Salmonella, Yersinia species, and Bordetella.

Type Four Secretion System

• Functions as a contact-dependent system.
• Transfers molecules across the cell envelope.
• There are three types of type four secretion systems:
• Conjugation: transfers DNA from one cell to another, a key method for bacteria to spread antibiotic resistance.
• Transformation: mediates DNA uptake.
• Transfers molecules to host cells in order to modify the microenvironment, benefiting intracellular bacteria survival.

Immune Avoidance via Secretion Systems

• Type three and four secretion systems allow bacteria to avoid immune responses by modifying host cell machinery.
• These modifications increase the bacteria's pathogenicity.
• A common feature is the modification of the host cytoskeleton, done by directly or indirectly manipulating cytoplasmic machinery.

Bacterial Invasion

• Bacterial invasion offers a survival advantage by avoiding the immune system inside a host cell.
• This follows the direct attachment of bacteria to the epithelium.
• Type three secretion systems inject effector proteins into the host.
• Salmonella and Shigella promote their uptake into non-phagocytic cells.
• They target pathways that promote pathogen engulfment and intracellular survival.
• Type three and four-dependent invasion and survival lead to bacterial persistence and damage to host tissues, such as necrosis and apoptosis.
• Antibiotic resistance and virulence genes are transferred via secretion systems.

Type Three Secretion Systems in Salmonella

• Many bacterial pathogens use molecular syringes in their membranes to inject proteins into host cell cytoplasm.
• In Salmonella enterica, type three secretion allows the bacterium to invade a eukaryotic host cell and become an intracellular parasite.
• The system includes various proteins arranged into a microscopic needle.
• The needle's base spans the inner and outer bacterial membranes.
• The needle, made up of multiple subunits of a single protein, projects away from the cell.
• Contact with the host cell is needed to start secretion.
• Contact transmits a signal through the needle, triggering a pore to form in the host cell's plasma membrane.
• Salmonella uses its type three secretion system to deliver at least 13 different protein toxins, called effector proteins, directly into the host cell's cytosol.
• Chaperone proteins deliver effector proteins in a loosely folded state to the base of the needle.
• An ATPase triggers the release of the effector proteins, helping them to unfold and travel through the needle's narrow channel.
• Direct delivery to the host cell's cytoplasm prevents dilution of the toxin.
• Inside cells in the gut, effector proteins interfere with signal transduction and modulate the host's response.
• Effectors induce cytoskeletal rearrangements causing the host cell membrane to ruffle around the microbe, leading to bacterial engulfment.
• Once inside the cell, Salmonella resides in a vacuole called the phagosome.
• Salmonella uses another type three secretion system to inject proteins that alter vesicle trafficking, reducing phagocytosis.
• The genes that encode the type three systems are on pathogenicity islands on the bacterial chromosome.
• Pathogenicity islands are inherited from other microorganisms.
• E. coli has acquired several pathogenicity islands that are absent from harmless strains.

Additional Information

• Adhesion: The process by which microorganisms attach to cells.
• Iatrogenic infections: Infections that occur as a direct result of medical treatment or procedures.
• Biofilms: Develop in hospital settings on medical devices that enter the body, such as catheters.
• Biofilms are a concern due to their resistance against treatments for bacterial infections.
• Biofilms often form on medical equipment like catheters, ventilators, and surgical implants, as well as on surfaces in the hospital.
• Thick ECMs protect bacteria from treatments like antibiotics, helping them survive.
• Bacteria in biofilms do not replicate, which allows them to evade the immune system and treatments that target replicating cells.