Type II secretion: the substrates that won't go away

Rondelet, Arnaud; Condemine, Guy

doi:10.1016/j.resmic.2013.03.005

Cited by 40 publications

(43 citation statements)

References 41 publications

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“…S1 in the supplemental material). This perhaps is expected, considering that the T2SS in many bacteria translocates to the extracellular milieu hydrolytic enzymes, such as cellulases, xylanases, and chitinases, which are responsible for digestion of insoluble polymers (4,(56)(57)(58)(59).…”

Section: Discussionmentioning

confidence: 98%

A Metalloprotease Secreted by the Type II Secretion System Links Vibrio cholerae with Collagen

et al. 2015

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bVibrio cholerae is autochthonous to various aquatic niches and is the etiological agent of the life-threatening diarrheal disease cholera. The persistence of V. cholerae in natural habitats is a crucial factor in the epidemiology of cholera. In contrast to the well-studied V. cholerae-chitin connection, scarce information is available about the factors employed by the bacteria for the interaction with collagens. Collagens might serve as biologically relevant substrates, because they are the most abundant protein constituents of metazoan tissues and V. cholerae has been identified in association with invertebrate and vertebrate marine animals, as well as in a benthic zone of the ocean where organic matter, including collagens, accumulates. Here, we describe the characterization of the V. cholerae putative collagenase, VchC, encoded by open reading frame VC1650 and belonging to the subfamily M9A peptidases. Our studies demonstrate that VchC is an extracellular collagenase degrading native type I collagen of fish and mammalian origin. Alteration of the predicted catalytic residues coordinating zinc ions completely abolished the protein enzymatic activity but did not affect the translocation of the protease by the type II secretion pathway into the extracellular milieu. We also show that the protease undergoes a maturation process with the aid of a secreted factor(s). Finally, we propose that V. cholerae is a collagenovorous bacterium, as it is able to utilize collagen as a sole nutrient source. This study initiates new lines of investigations aiming to uncover the structural and functional components of the V. cholerae collagen utilization program. Members of the genus Vibrio are important inhabitants of the marine coastal waters, estuaries, and ocean sediments, with some pathogenic species also causing wound infections, primary septicemia, gastroenteritis, and diarrhea in humans (1, 2). Among the more than 200 serogroups of V. cholerae, only O1 and O139 are recognized as agents of cholera, a potentially life-threatening diarrheal disease. Cholera remains a significant public health problem by affecting millions of people annually, predominantly in developing countries that have limited clean water supplies and poor sanitation (3). Infection of the human host occurs upon ingestion of water or food contaminated with the bacterium. Following colonization of the small intestine, V. cholerae utilizes a multicomponent secretory pathway, the type II secretion system (T2SS), to release cholera toxin. Cholera toxin induces acute diarrhea in people infected with cholera, enabling the bacteria to escape from the host into the aquatic reservoir (4). During interepidemic periods, V. cholerae persists freely or in association with various aquatic organisms, including copepods, insect egg masses, shellfish, and vertebrate fish (5-7). Extracellular proteins, including those secreted by the T2SS, have been implicated in facilitating the fitness of V. cholerae in both the human host and aquatic niches (4,6,8). The array of extrace...

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Section: Discussionmentioning

confidence: 98%

A Metalloprotease Secreted by the Type II Secretion System Links Vibrio cholerae with Collagen

et al. 2015

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“…This occurs by cascades of reactions, which lead to degradation of RseA and release of E to allow it to bind to the core RNA polymerase (RNAP). T2S is a unique secretion pathway that, in addition to transporting soluble exoproteins, handles membrane-anchored proteins (6). In this respect, linking the T2S pathway with a sigma factor that deals with cell envelope stress may have important functional implications.…”

Section: Discussionmentioning

confidence: 99%

“…This secretory pathway is responsible for the passage of folded and/or oligomeric cargo proteins (exoproteins and T2S substrates) from the periplasm across the outer membrane. After translocation, the T2S substrates are either released to the extracellular milieu or remain anchored to the bacterial cell surface (6). The array of T2S exoproteins is comprised of toxins, enzymes capable of breaking down a variety of biological materials, and lipoproteins participating in respiration and/or biofilm formation, as well as proteins facilitating bacterial attachment to biotic and abiotic surfaces (2)(3)(4)6).…”

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confidence: 99%

The Type II Secretion Pathway in Vibrio cholerae Is Characterized by Growth Phase-Dependent Expression of Exoprotein Genes and Is Positively Regulated by σ ^E

et al. 2014

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c Vibrio cholerae, an etiological agent of cholera, circulates between aquatic reservoirs and the human gastrointestinal tract. The type II secretion (T2S) system plays a pivotal role in both stages of the lifestyle by exporting multiple proteins, including cholera toxin. Here, we studied the kinetics of expression of genes encoding the T2S system and its cargo proteins. We have found that under laboratory growth conditions, the T2S complex was continuously expressed throughout V. cholerae growth, whereas there was growth phase-dependent transcriptional activity of genes encoding different cargo proteins. Moreover, exposure of V. cholerae to different environmental cues encountered by the bacterium in its life cycle induced transcriptional expression of T2S. Subsequent screening of a V. cholerae genomic library suggested that E stress response, phosphate metabolism, and the second messenger 3=,5=-cyclic diguanylic acid (c-di-GMP) are involved in regulating transcriptional expression of T2S. Focusing on E , we discovered that the upstream region of the T2S operon possesses both the consensus E and 70 signatures, and deletion of the E binding sequence prevented transcriptional activation of T2S by RpoE. Ectopic overexpression of E stimulated transcription of T2S in wild-type and isogenic ⌬rpoE strains of V. cholerae, providing additional support for the idea that the T2S complex belongs to the E regulon. Together, our results suggest that the T2S pathway is characterized by the growth phase-dependent expression of genes encoding cargo proteins and requires a multifactorial regulatory network to ensure appropriate kinetics of the secretory traffic and the fitness of V. cholerae in different ecological niches.

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“…In addition, A. baumannii possesses genes for a type II secretion (T2S) system (24,25). Bacteria that use the T2S system are typically environmental bacteria; however, they also include pathogens such as Vibrio cholerae, enterotoxigenic Escherichia coli, Pseudomonas aeruginosa, and Legionella pneumophila (26)(27)(28)(29). The T2S system mediates the secretion of toxins and hydrolytic enzymes, including proteases, lipases, lipoproteins, and enzymes that break down complex carbohydrates, and has been found to be required for in vivo survival and virulence (30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”

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confidence: 99%

Acinetobacter baumannii Is Dependent on the Type II Secretion System and Its Substrate LipA for Lipid Utilization and In Vivo Fitness

et al. 2016

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Gram-negative bacteria express a number of sophisticated secretion systems to transport virulence factors across the cell envelope, including the type II secretion (T2S) system. Genes for the T2S components GspC through GspN and PilD are conserved among isolates of Acinetobacter baumannii, an increasingly common nosocomial pathogen that is developing multidrug resistance at an alarming rate. In contrast to most species, however, the T2S genes are dispersed throughout the genome rather than linked into one or two operons. Despite this unique genetic organization, we show here that the A. baumannii T2S system is functional. Deletion of gspD or gspE in A. baumannii ATCC 17978 results in loss of secretion of LipA, a lipase that breaks down long-chain fatty acids. Due to a lack of extracellular lipase, the gspD mutant, the gspE mutant, and a lipA deletion strain are incapable of growth on long-chain fatty acids as a sole source of carbon, while their growth characteristics are indistinguishable from those of the wild-type strain in nutrient-rich broth. Genetic inactivation of the T2S system and its substrate, LipA, also has a negative impact on in vivo fitness in a neutropenic murine model for bacteremia. Both the gspD and lipA mutants are outcompeted by the wild-type strain as judged by their reduced numbers in spleen and liver following intravenous coinoculation. Collectively, our findings suggest that the T2S system plays a hitherto-unrecognized role in in vivo survival of A. baumannii by transporting a lipase that may contribute to fatty acid metabolism. IMPORTANCEInfections by multidrug-resistant Acinetobacter baumannii are a growing health concern worldwide, underscoring the need for a better understanding of the molecular mechanisms by which this pathogen causes disease. In this study, we demonstrated that A. baumannii expresses a functional type II secretion (T2S) system that is responsible for secretion of LipA, an extracellular lipase required for utilization of exogenously added lipids. The T2S system and the secreted lipase support in vivo colonization and thus contribute to the pathogenic potential of A. baumannii.

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Type II secretion: the substrates that won't go away

Cited by 40 publications

References 41 publications

A Metalloprotease Secreted by the Type II Secretion System Links Vibrio cholerae with Collagen

A Metalloprotease Secreted by the Type II Secretion System Links Vibrio cholerae with Collagen

The Type II Secretion Pathway in Vibrio cholerae Is Characterized by Growth Phase-Dependent Expression of Exoprotein Genes and Is Positively Regulated by σ ^E

Acinetobacter baumannii Is Dependent on the Type II Secretion System and Its Substrate LipA for Lipid Utilization and In Vivo Fitness

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Type II secretion: the substrates that won't go away

Cited by 40 publications

References 41 publications

A Metalloprotease Secreted by the Type II Secretion System Links Vibrio cholerae with Collagen

A Metalloprotease Secreted by the Type II Secretion System Links Vibrio cholerae with Collagen

The Type II Secretion Pathway in Vibrio cholerae Is Characterized by Growth Phase-Dependent Expression of Exoprotein Genes and Is Positively Regulated by σ E

Acinetobacter baumannii Is Dependent on the Type II Secretion System and Its Substrate LipA for Lipid Utilization and In Vivo Fitness

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The Type II Secretion Pathway in Vibrio cholerae Is Characterized by Growth Phase-Dependent Expression of Exoprotein Genes and Is Positively Regulated by σ ^E