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Listeria monocytogenes virulence factor secretion: don't leave the cell without a chaperone.

Cahoon LA, Freitag NE - Front Cell Infect Microbiol (2014)

Bottom Line: Here, proteins must be folded and often further delivered across the matrix of the cell wall.PrsA2 is a member of a family of membrane-associated lipoproteins that contribute to the folding and stability of secreted proteins as they cross the bacterial membrane.PrsA2 contributes to the integrity of the L. monocytogenes cell wall as well as swimming motility and bacterial resistance to osmotic stress; however its most critical role may be its requirement for L. monocytogenes virulence and viability within host cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago Chicago, IL, USA.

ABSTRACT
In Gram-positive bacteria, the secretion of proteins requires translocation of polypeptides across the bacterial membrane into the highly charged environment of the membrane-cell wall interface. Here, proteins must be folded and often further delivered across the matrix of the cell wall. While many aspects of protein secretion have been well studied in Gram-negative bacteria which possess both an inner and outer membrane, generally less attention has been given to the mechanics of protein secretion across the single cell membrane of Gram-positive bacteria. In this review, we focus on the role of a post-translocation secretion chaperone in Listeria monocytogenes known as PrsA2, and compare what is known regarding PrsA2 with PrsA homologs in other Gram-positive bacteria. PrsA2 is a member of a family of membrane-associated lipoproteins that contribute to the folding and stability of secreted proteins as they cross the bacterial membrane. PrsA2 contributes to the integrity of the L. monocytogenes cell wall as well as swimming motility and bacterial resistance to osmotic stress; however its most critical role may be its requirement for L. monocytogenes virulence and viability within host cells. A better understanding of the role of PrsA2 and PrsA-like homologs will provide insight into the dynamics of protein folding and stability in Gram-positive bacteria and may result in new strategies for optimizing protein secretion as well as inhibiting the production of virulence factors.

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Working model for the multiple roles of PrsA2 in L. monocytogenes. A cartoon of a single L. monocytogenes cell is shown in the environment and in the host, with PrsA2 both tethered to the cell membrane and secreted. When L. monocytogenes is in the outside environment, PrsA2 directly or indirectly is required for functional penicillin binding proteins (PBP), flagellin, and other factors that contribute to cell wall integrity, swimming motility, and resistance to osmotic stress. When L. monocytogenes is in the host, activation of the central virulence regulatory protein PrfA leads to increased expression of several secreted virulence factors as well as PrsA2, which is required for the folding and stability of listeriolysin (LLO), the Mpl protease that activates the broad-range phospholipase (PlcB), ActA, and other factors.
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Figure 4: Working model for the multiple roles of PrsA2 in L. monocytogenes. A cartoon of a single L. monocytogenes cell is shown in the environment and in the host, with PrsA2 both tethered to the cell membrane and secreted. When L. monocytogenes is in the outside environment, PrsA2 directly or indirectly is required for functional penicillin binding proteins (PBP), flagellin, and other factors that contribute to cell wall integrity, swimming motility, and resistance to osmotic stress. When L. monocytogenes is in the host, activation of the central virulence regulatory protein PrfA leads to increased expression of several secreted virulence factors as well as PrsA2, which is required for the folding and stability of listeriolysin (LLO), the Mpl protease that activates the broad-range phospholipase (PlcB), ActA, and other factors.

Mentions: In Gram-positive bacteria, most secreted proteins are thought to cross the single bacterial cell membrane in an unfolded state to enter the space that exists between the cell membrane and the cell wall (Matias and Beveridge, 2005, 2006). This inner wall space characteristically contains high concentrations of cations bound to teichoic acid, a high density of negative charge, and a low pH which presents a challenging environment for protein folding and function (Sarvas et al., 2004). The proposed function of L. monocytogenes PrsA2 and related PrsA-like proteins in other Gram-positive bacteria is to promote post-membrane translocation protein folding and maintain optimal secretion homeostasis. Although L. monocytogenes PrsA2 contributes to several aspects of L. monocytogenes physiology during bacterial growth in broth culture or on solid media, its most striking contributions are detected during bacterial infection of mammalian cells where it is essential for the folding and activity of secreted proteins required for bacterial virulence and intracellular bacterial replication (Alonzo et al., 2009, 2011; Zemansky et al., 2009; Alonzo and Freitag, 2010) (Figure 4).


Listeria monocytogenes virulence factor secretion: don't leave the cell without a chaperone.

Cahoon LA, Freitag NE - Front Cell Infect Microbiol (2014)

Working model for the multiple roles of PrsA2 in L. monocytogenes. A cartoon of a single L. monocytogenes cell is shown in the environment and in the host, with PrsA2 both tethered to the cell membrane and secreted. When L. monocytogenes is in the outside environment, PrsA2 directly or indirectly is required for functional penicillin binding proteins (PBP), flagellin, and other factors that contribute to cell wall integrity, swimming motility, and resistance to osmotic stress. When L. monocytogenes is in the host, activation of the central virulence regulatory protein PrfA leads to increased expression of several secreted virulence factors as well as PrsA2, which is required for the folding and stability of listeriolysin (LLO), the Mpl protease that activates the broad-range phospholipase (PlcB), ActA, and other factors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921577&req=5

Figure 4: Working model for the multiple roles of PrsA2 in L. monocytogenes. A cartoon of a single L. monocytogenes cell is shown in the environment and in the host, with PrsA2 both tethered to the cell membrane and secreted. When L. monocytogenes is in the outside environment, PrsA2 directly or indirectly is required for functional penicillin binding proteins (PBP), flagellin, and other factors that contribute to cell wall integrity, swimming motility, and resistance to osmotic stress. When L. monocytogenes is in the host, activation of the central virulence regulatory protein PrfA leads to increased expression of several secreted virulence factors as well as PrsA2, which is required for the folding and stability of listeriolysin (LLO), the Mpl protease that activates the broad-range phospholipase (PlcB), ActA, and other factors.
Mentions: In Gram-positive bacteria, most secreted proteins are thought to cross the single bacterial cell membrane in an unfolded state to enter the space that exists between the cell membrane and the cell wall (Matias and Beveridge, 2005, 2006). This inner wall space characteristically contains high concentrations of cations bound to teichoic acid, a high density of negative charge, and a low pH which presents a challenging environment for protein folding and function (Sarvas et al., 2004). The proposed function of L. monocytogenes PrsA2 and related PrsA-like proteins in other Gram-positive bacteria is to promote post-membrane translocation protein folding and maintain optimal secretion homeostasis. Although L. monocytogenes PrsA2 contributes to several aspects of L. monocytogenes physiology during bacterial growth in broth culture or on solid media, its most striking contributions are detected during bacterial infection of mammalian cells where it is essential for the folding and activity of secreted proteins required for bacterial virulence and intracellular bacterial replication (Alonzo et al., 2009, 2011; Zemansky et al., 2009; Alonzo and Freitag, 2010) (Figure 4).

Bottom Line: Here, proteins must be folded and often further delivered across the matrix of the cell wall.PrsA2 is a member of a family of membrane-associated lipoproteins that contribute to the folding and stability of secreted proteins as they cross the bacterial membrane.PrsA2 contributes to the integrity of the L. monocytogenes cell wall as well as swimming motility and bacterial resistance to osmotic stress; however its most critical role may be its requirement for L. monocytogenes virulence and viability within host cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago Chicago, IL, USA.

ABSTRACT
In Gram-positive bacteria, the secretion of proteins requires translocation of polypeptides across the bacterial membrane into the highly charged environment of the membrane-cell wall interface. Here, proteins must be folded and often further delivered across the matrix of the cell wall. While many aspects of protein secretion have been well studied in Gram-negative bacteria which possess both an inner and outer membrane, generally less attention has been given to the mechanics of protein secretion across the single cell membrane of Gram-positive bacteria. In this review, we focus on the role of a post-translocation secretion chaperone in Listeria monocytogenes known as PrsA2, and compare what is known regarding PrsA2 with PrsA homologs in other Gram-positive bacteria. PrsA2 is a member of a family of membrane-associated lipoproteins that contribute to the folding and stability of secreted proteins as they cross the bacterial membrane. PrsA2 contributes to the integrity of the L. monocytogenes cell wall as well as swimming motility and bacterial resistance to osmotic stress; however its most critical role may be its requirement for L. monocytogenes virulence and viability within host cells. A better understanding of the role of PrsA2 and PrsA-like homologs will provide insight into the dynamics of protein folding and stability in Gram-positive bacteria and may result in new strategies for optimizing protein secretion as well as inhibiting the production of virulence factors.

Show MeSH
Related in: MedlinePlus