Secretion Systems for Transport of Proteins and Other Substances Outside the Bacterial Cells


Intensive metabolism of bacteria requires continious controlled transport of bacterial high molecular weight substances (primarily, proteins) out of the microbial cells to the extracellular environment. A tremendous number of biologically active molecules is secreted by bacteria (enzymes, toxins, signalling messengers, genetic elements and plenty of others). They play the decisive role in bacterial physiology and pathology.

Well-studied are various types of protein secretion systems, organized in gram-negative bacterial cells.

To date, 7 types of secretion systems for proteins are found; six of them are the attributes of gram-negative bacteria, whereas type VII is determined in mycobacteria.

Bacterial secretion systems include translocator and effector proteins. Translocator proteins build the structural units of secretion systems and serve for their proper function, thus providing the transport of effector proteins. Effector proteins are biologically active molecules (enzymes ot toxins) that are secreted by bacteria and develop their specific activity outside the bacterial cell. Types I-VI of protein secretion in gram-negative bacteria are different in their structure and function. Overall, gram-negative cell wall with its hydrophobic outer membrane and LPS creates a serious barrier on the way of translocated proteins.

In this vein, the types I, III and VI perform one-step secretion of proteins across the envelop of gram-negative bacteria, whereas the types II, IV and V elaborate two-step secretion; in latter case the proteins are first delivered into periplasmic space and next transported out of the microbial cell across the outer membrane.

The most simple is type I secretion system (or T1SS). It includes 3 distinct proteins – cytoplasmic membrane ATPase with ATP-binding cassette (ABC-transporter protein) that initiates the process and provides energy for molecular transport; membrane fusion protein that makes the channel, penetrating the periplasmic space; and outer membrane protein, located within the outer membrane. The last protein plays a role of a “gatekeeper” of channel outlet, switching its activity into proper state.

T1SS provides the excretion of certain groups of toxins (predominantly, hemolysins) by gram-negative bacteria.

The types III and VI of protein secretion are the basic systems for delivery of bacterial virulence factors into affected cells. They make injectisome or “needle complex” protruding outside from bacterial cell. After primary contact with the membrane of the host cell, the needle complex activates and injects the effector virulence proteins into target host cells.

Most of gram-negative bacteria (e.g., shigellae, salmonellae, or Pseudomonas aeruginosa) use these pathways for secretion of multiple virulence factors.

The systems of II, V and partially of IV types (with two-step secretion of molecules) use special secretory or Sec proteins for initial transport of proteins from the cytoplasm into periplasmic space. The transported molecules are primarily synthesized on the ribosomes as pre-proteins. These pre-proteins bear additional signal sequence that prevent their degradation during transport. At first step Sec-proteins deliver them into periplasmic space, where the signal sequence is removed by proteolysis. At second step the molecule is transported across the outer membrane outside the cell.

T2SS facilitates the secretion of extremely high variety of molecules by gram-negative bacteria. Among them are enzymes (e.g., phospholipase C of P. aeruginosa) and toxins (e.g., Vibrio cholerae toxin). Thus, T2SS is denoted as “general secretory pathway” in gram-negative bacteria.

T5SS is responsible for secretion of several enzymes and toxins, such as vacuolating or Vac toxin of Helicobacter pylori. Unlike other pathways, the secreted proteins of T5SS, if appeared in periplasmic space, play a further role of autotransporters – the tail part of transported molecule makes a channel within the outer membrane and provides its final excretion.

The activity of T4SS resembles to some extent the bacterial conjugation. Therefore, T4SS delivers not only the vast number of virulence proteins (e.g., Cag toxin of H. pylori, the toxins of pertussis bacteria or legionellas) but also the mobile genetic elements to the recipient bacteria. The exchange of genetic material accelerates the adaptive capacity of bacterial strains including the spread of the resistance to antibiotics and antiseptics.

The secretion of proteins in gram-positive bacteria is not completely elucidated. They may perform direct protein secretion via the channels within peptidoglycan cell wall. Futhermore, according to the currently known data, gram-positive microbes use the similar principles of protein secretion as gram-negative bacteria. For instance, they use Sec-proteins for protein translocation across the cytoplasmic membrane. After the removal of signal sequences, the transported proteins are introduced into external layers of the cell wall.

Recently a new type VII secretion system (T7SS) was described in M. tuberculosis. It is capable of secreting mycobacterial toxic proteins that provide the survival of mycobacteria within phagocytes. Homologous systems were also found in pathogenic cocci, e.g. S. aureus.