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Bacterial Secretion Systems: An Overview, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555819286/9781555819279_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555819286/9781555819279_Chap08-2.gifAbstract:
One essential prokaryotic cell function is the transport of proteins from the cytoplasm into other compartments of the cell, the environment, and/or other bacteria or eukaryotic cells—a process known as protein secretion. Prokaryotes have developed numerous ways of transporting protein cargo between locations, which largely involve the assistance of dedicated protein secretion systems. Protein secretion systems are essential for the growth of bacteria and are used in an array of processes. Some secretion systems are found in almost all bacteria and secrete a wide variety of substrates, while others have been identified in only a small number of bacterial species or are dedicated to secreting only one or a few proteins. In certain cases, these dedicated secretion systems are used by bacterial pathogens to manipulate the host and establish a replicative niche. Other times, they are required to take advantage of an environmental niche, perhaps by secreting proteins that help bacteria to compete with nearby microorganisms. There are several different classes of bacterial secretion systems, and their designs can differ based on whether their protein substrates cross a single phospholipid membrane, two membranes, or even three membranes, where two are bacterial and one is a host membrane. Due to the specificity of expression of some of these secretion systems in bacterial pathogens, antimicrobials are being developed against these systems to augment our current repertoire of antibiotics. This topic is discussed in Section VII, “Targeted Therapies”.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Full text loading...
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Export through the Sec pathway. In bacteria, the Sec pathway transports unfolded proteins across the cytoplasmic membrane. Proteins secreted by this pathway may either become embedded in the inner membrane or will be released into the periplasm. In Gram-negative organisms, these periplasmic proteins may be released extracellularly with the help of an additional secretion system. (A) Proteins destined for the periplasm (or extracellular release) are translocated by a posttranslational mechanism and contain a removable signal sequence recognized by the SecB protein. SecB binds presecretory proteins and prevents them from folding while also delivering its substrates to SecA. SecA both guides proteins to the SecYEG channel and serves as the ATPase that provides the energy for protein translocation. Following transport through the SecYEG channel, proteins are folded in the periplasm. (B) The Sec pathway utilizes a cotranslational mechanism of export to secrete proteins destined for the inner membrane. These proteins contain a signal sequence recognized by the signal recognition particle (SRP). During translation, the SRP binds target proteins as they emerge from the ribosome and recruits the docking protein FtsY. FtsY delivers the ribosome-protein complex to the SecYEG channel, which translocates the nascent protein across the cytoplasmic membrane. During translocation across the channel, the transmembrane domain is able to escape through the side of the channel into the membrane, where the protein remains attached.
Export through the Sec pathway. In bacteria, the Sec pathway transports unfolded proteins across the cytoplasmic membrane. Proteins secreted by this pathway may either become embedded in the inner membrane or will be released into the periplasm. In Gram-negative organisms, these periplasmic proteins may be released extracellularly with the help of an additional secretion system. (A) Proteins destined for the periplasm (or extracellular release) are translocated by a posttranslational mechanism and contain a removable signal sequence recognized by the SecB protein. SecB binds presecretory proteins and prevents them from folding while also delivering its substrates to SecA. SecA both guides proteins to the SecYEG channel and serves as the ATPase that provides the energy for protein translocation. Following transport through the SecYEG channel, proteins are folded in the periplasm. (B) The Sec pathway utilizes a cotranslational mechanism of export to secrete proteins destined for the inner membrane. These proteins contain a signal sequence recognized by the signal recognition particle (SRP). During translation, the SRP binds target proteins as they emerge from the ribosome and recruits the docking protein FtsY. FtsY delivers the ribosome-protein complex to the SecYEG channel, which translocates the nascent protein across the cytoplasmic membrane. During translocation across the channel, the transmembrane domain is able to escape through the side of the channel into the membrane, where the protein remains attached.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Secretion through the Tat pathway. Bacteria secrete folded proteins across the cytoplasmic membrane using the Tat secretion pathway. This pathway consists of two or three components (TatA, TatB, and TatC). In Gram-negative bacteria, TatB and TatC bind a specific N-terminal signal peptide containing a “twin” arginine motif on folded Tat secretion substrates. TatB and TatC then recruit TatA to the cytoplasmic membrane, where it forms a channel. Folded proteins are then translocated across the channel and into the periplasm. In Gram-negative bacteria, these proteins may remain in the periplasm or can be exported out of the cell by the T2SS.
Secretion through the Tat pathway. Bacteria secrete folded proteins across the cytoplasmic membrane using the Tat secretion pathway. This pathway consists of two or three components (TatA, TatB, and TatC). In Gram-negative bacteria, TatB and TatC bind a specific N-terminal signal peptide containing a “twin” arginine motif on folded Tat secretion substrates. TatB and TatC then recruit TatA to the cytoplasmic membrane, where it forms a channel. Folded proteins are then translocated across the channel and into the periplasm. In Gram-negative bacteria, these proteins may remain in the periplasm or can be exported out of the cell by the T2SS.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Secretion systems in Gram-negative bacteria. Gram-negative bacteria utilize a number of dedicated protein secretion systems to transport proteins across one, two, or three phospholipid membranes. Some proteins are secreted in a two-step, Sec- or Tat-dependent mechanism. These proteins cross the inner membrane with the help of either the Sec or Tat secretion pathways and are then transported across the outer membrane using a second secretion system. The T2SS and T5SS secrete proteins in this manner. Because it secretes folded substrates, the T2SS translocates proteins initially transported by either the Tat or Sec pathway (where Sec substrates are folded in the periplasm). In contrast, autotransporters of the T5SS must be unfolded prior to outer membrane transport and thus must be secreted across the inner membrane by the Sec pathway. Additionally, several Gram-negative protein secretion systems transport their substrates across both bacterial membranes in a one-step, Sec- or Tat-independent process. These include the T1SS, T3SS, T4SS, and T6SS. All of these pathways contain periplasm-spanning channels and secrete proteins from the cytoplasm outside the cell, but their mechanisms of protein secretion are quite different. Three of these secretion systems, the T3SS, T4SS, and T6SS, can also transport proteins across an additional host cell membrane, delivering secreted proteins directly to the cytosol of a target cell.
Secretion systems in Gram-negative bacteria. Gram-negative bacteria utilize a number of dedicated protein secretion systems to transport proteins across one, two, or three phospholipid membranes. Some proteins are secreted in a two-step, Sec- or Tat-dependent mechanism. These proteins cross the inner membrane with the help of either the Sec or Tat secretion pathways and are then transported across the outer membrane using a second secretion system. The T2SS and T5SS secrete proteins in this manner. Because it secretes folded substrates, the T2SS translocates proteins initially transported by either the Tat or Sec pathway (where Sec substrates are folded in the periplasm). In contrast, autotransporters of the T5SS must be unfolded prior to outer membrane transport and thus must be secreted across the inner membrane by the Sec pathway. Additionally, several Gram-negative protein secretion systems transport their substrates across both bacterial membranes in a one-step, Sec- or Tat-independent process. These include the T1SS, T3SS, T4SS, and T6SS. All of these pathways contain periplasm-spanning channels and secrete proteins from the cytoplasm outside the cell, but their mechanisms of protein secretion are quite different. Three of these secretion systems, the T3SS, T4SS, and T6SS, can also transport proteins across an additional host cell membrane, delivering secreted proteins directly to the cytosol of a target cell.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Four secretion systems in Gram-positive bacteria. Gram-positive bacteria contain a single cytoplasmic membrane surrounded by a very thick cell wall. These organisms can secrete proteins across the membrane using the Tat and Sec secretion systems. In contrast to Gram-negative organisms, many Gram-positive bacteria use an additional factor for Sec secretion of a smaller subset of proteins, called SecA2. Additionally, there is evidence that some Gram-positive bacteria may use dedicated secretion apparatuses, called “injectosomes” to transport proteins from the bacterial cytoplasm into the cytoplasm of a host cell in a two-step process. The specific mechanism of this process has not been determined, though it has been proposed that the injectosome may utilize a protected channel to transport proteins across the cell wall during export.
Four secretion systems in Gram-positive bacteria. Gram-positive bacteria contain a single cytoplasmic membrane surrounded by a very thick cell wall. These organisms can secrete proteins across the membrane using the Tat and Sec secretion systems. In contrast to Gram-negative organisms, many Gram-positive bacteria use an additional factor for Sec secretion of a smaller subset of proteins, called SecA2. Additionally, there is evidence that some Gram-positive bacteria may use dedicated secretion apparatuses, called “injectosomes” to transport proteins from the bacterial cytoplasm into the cytoplasm of a host cell in a two-step process. The specific mechanism of this process has not been determined, though it has been proposed that the injectosome may utilize a protected channel to transport proteins across the cell wall during export.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015The T7SS. Certain Gram-positive organisms, including members of the genus Mycobacteria, contain a cell wall layer that is heavily modified by lipids, called a mycomembrane. These organisms contain a distinct protein secretion apparatus called a T7SS. T7SSs contain several core inner membrane proteins that interact with cytosolic chaperones and form a channel through which proteins are secreted. Additionally, it has been proposed that T7SSs may contain an additional, mycomembrane-spanning channel that aids in extracellular secretion of substrates, though this model has not been experimentally proven.
The T7SS. Certain Gram-positive organisms, including members of the genus Mycobacteria, contain a cell wall layer that is heavily modified by lipids, called a mycomembrane. These organisms contain a distinct protein secretion apparatus called a T7SS. T7SSs contain several core inner membrane proteins that interact with cytosolic chaperones and form a channel through which proteins are secreted. Additionally, it has been proposed that T7SSs may contain an additional, mycomembrane-spanning channel that aids in extracellular secretion of substrates, though this model has not been experimentally proven.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Mechanisms of innate immune recognition of bacterial secretion systems. To distinguish between pathogenic and commensal bacteria, the mammalian innate immune system has developed methods to directly recognize patterns unique to bacterial pathogens, such as the use of protein secretion apparatuses. The immune system can sense several facets of bacterial protein secretion. These include the pore formation by secretion systems or secreted proteins, aberrant translocation of bacterial molecules into the cytosol, the presence of effector proteins and/or their activities, as well as the components of the secretion systems themselves.
Mechanisms of innate immune recognition of bacterial secretion systems. To distinguish between pathogenic and commensal bacteria, the mammalian innate immune system has developed methods to directly recognize patterns unique to bacterial pathogens, such as the use of protein secretion apparatuses. The immune system can sense several facets of bacterial protein secretion. These include the pore formation by secretion systems or secreted proteins, aberrant translocation of bacterial molecules into the cytosol, the presence of effector proteins and/or their activities, as well as the components of the secretion systems themselves.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015Classes of bacterial protein secretion systems
Classes of bacterial protein secretion systems
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0012-2015