Carbon Catabolite Repression of Type IV Pilus-Dependent Gliding Motility in the Anaerobic Pathogen
            <i>Clostridium perfringens</i>

Méndez, Marcelo; Huang, I-Hsiu; Ohtani, Kaori; Grau, Roberto; Shimizu, Tohru; Sarker, Mahfuzur R.

doi:10.1128/jb.01407-07

Cited by 47 publications

(32 citation statements)

References 53 publications

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“…In Grampositive bacteria, CCR is mostly achieved through a global regulator, CcpA (8,15). It has been found that CcpA not only acts as a master regulator of catabolite control, but also controls the expression of virulence genes in many pathogens, such as the sagA operon (for streptolysin S production) (17) and the mac gene (encoding immunoglobulin-degrading enzyme) (32) in Streptococcus pyogenes and the pilT and pilD genes (for pilus components) in Clostridium perfringens (26). Similarly, CcpA also regulates virulence-related functions in oral streptococci, e.g., biofilm formation and acid tolerance in S. mutans (2) and penicillin tolerance (6), H 2 O 2 production (50), and the arginine deaminase (12) pathway in S. gordonii.…”

Section: Discussionmentioning

confidence: 99%

CcpA-Dependent Carbohydrate Catabolite Repression Regulates Galactose Metabolism in Streptococcus oligofermentans

Cai

Tong

et al. 2012

J Bacteriol

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bStreptococcus oligofermentans is an oral commensal that inhibits the growth of the caries pathogen Streptococcus mutans by producing copious amounts of H 2 O 2 and that grows faster than S. mutans on galactose. In this study, we identified a novel eightgene galactose (gal) operon in S. oligofermentans that was comprised of lacABCD, lacX, and three genes encoding a galactosespecific transporter. Disruption of lacA caused more growth reduction on galactose than mutation of galK, a gene in the Leloir pathway, indicating that the principal role of this operon is in galactose metabolism. Diauxic growth was observed in cultures containing glucose and galactose, and a luciferase reporter fusion to the putative gal promoter demonstrated 12-fold repression of the operon expression by glucose but was induced by galactose, suggesting a carbon catabolite repression (CCR) control in galactose utilization. Interestingly, none of the single-gene mutations in the well-known CCR regulators ccpA and manL affected diauxic growth, although the operon expression was upregulated in these mutants in glucose. A double mutation of ccpA and manL eliminated glucose repression of galactose utilization, suggesting that these genes have parallel functions in regulating gal operon expression and mediating CCR. Electrophoretic mobility shift assays demonstrated binding of CcpA to the putative catabolite response element motif in the promoter regions of the gal operon and manL, suggesting that CcpA regulates CCR through direct regulation of the transcription of the gal operon and manL. This provides the first example of oral streptococci using two parallel CcpA-dependent CCR pathways in controlling carbohydrate metabolism.T he human oral cavity harbors between 700 and 19,000 operative taxonomic units (16,19,45), among which streptococci are the most abundant microorganisms, contributing about 80% of the total microbial population in the dental biofilm (5, 31). Complex interspecies competitions occur among the oral streptococci due to limited space and shared nutritional requirements (30,37,38,50). The outcome of these interspecies competitions may determine the health status of the oral cavity.Carbohydrates are common carbon and energy sources for all streptococci, and as such, differences in uptake and metabolic efficiency among the species affect each species' competitiveness in the oral biofilm. The carbohydrate metabolism of bacteria is usually under the control of carbon catabolite repression (CCR) (13,34,35,42), in which rapidly metabolizable carbohydrates, usually glucose, repress the utilization of nonpreferred carbohydrates. It is generally believed that catabolite control protein A (CcpA) (8, 15) and the histidine phosphocarrier protein HPr (9) function in the regulation of CCR in most low-GϩC Gram-positive bacteria. HPr phosphorylation (HPr-Ser-P) is triggered by fructose-1,6-bisphosphate (9), a glycolysis intermediate. In the presence of a preferred carbohydrate, i.e., glucose, HPr-Ser-P serves as a cofactor to assist CcpA binding ...

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Section: Discussionmentioning

confidence: 99%

CcpA-Dependent Carbohydrate Catabolite Repression Regulates Galactose Metabolism in Streptococcus oligofermentans

Cai

Tong

et al. 2012

J Bacteriol

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“…Video microscopy of the C. perfringens-C2C12 interactions under anaerobic conditions showed the bacteria were not lined up in the characteristic end-to-end fashion seen in motile C. perfringens cells (39) but rather floated in the tissue culture medium mostly as individual cells (see Video S5 in the supplemental material). We theorized that glucose, present in fresh DMEM at 4.5 g/liter, might be inhibiting the expression of motility genes, as previously reported (25,39). Therefore, we carried out the same assay using C2C12 cells that had been grown for 2 days in DMEM to deplete the glucose before placement in an anaerobic chamber.…”

Section: Methodsmentioning

confidence: 99%

Expression of a Clostridium perfringens Type IV Pilin by Neisseria gonorrhoeae Mediates Adherence to Muscle Cells

2011

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Clostridium perfringens is an anaerobic, Gram-positive bacterium that causes a range of diseases in humans, including lethal gas gangrene. We have recently shown that strains of C. perfringens move across the surface of agar plates by a unique type IV pilus (TFP)-mediated social motility that had not been previously described. Based on sequence homology to pilins in Gram-negative bacteria, C. perfringens appears to have two pilin subunits, PilA1 and PilA2. Structural prediction analysis indicated PilA1 is similar to the pseudopilin found in Klebsiella oxytoca, while PilA2 is more similar to true pilins found in the Gram-negative pathogens Pseudomonas aeruginosa and Neisseria gonorrhoeae. Strains of N. gonorrhoeae that were genetically deficient in the native pilin, PilE, but supplemented with inducible expression of PilA1 and PilA2 of C. perfringens were constructed. Genetic competence, wild-type twitching motility, and attachment to human urogenital epithelial cells were not restored by expression of either pilin. However, attachment to mouse and rat myoblast (muscle) cell lines was observed with the N. gonorrhoeae strain expressing PilA2. Significantly, wild-type C. perfringens cells adhered to mouse myoblasts under anaerobic conditions, and adherence was 10-fold lower in a pilT mutant that lacked functional TFP. These findings implicate C. perfringens TFP in the ability of C. perfringens to adhere to and move along muscle fibers in vivo, which may provide a therapeutic approach to limiting this rapidly spreading and highly lethal infection.

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“…This implies that the bacteria can sense when they are in contact with a surface and can modify their surface appendages, a feature shared by Pseudomonas aeruginosa, which produces more TFP on agar surfaces than in liquid media (7). Carbohydrates in the form of readily metabolizable hexoses act to suppress motility on agar plates, and this suppression is mediated via the carbohydrate catabolite regulatory protein, CcpA, in C. perfringens strain 13 (8). Interestingly, CcpA was also required for maximum motility in strain 13 in the absence of added sugar (8).…”

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confidence: 99%

Hypermotility in Clostridium perfringens Strain SM101 Is Due to Spontaneous Mutations in Genes Linked to Cell Division

et al. 2014

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Clostridium perfringens is a Gram-positive anaerobic pathogen of humans and animals. Although they lack flagella, C. perfringens bacteria can still migrate across surfaces using a type of gliding motility that involves the formation of filaments of bacteria lined up in an end-to-end conformation. In strain SM101, hypermotile variants are often found arising from the edges of colonies on agar plates. Hypermotile cells are longer than wild-type cells, and video microscopy of their gliding motility suggests that they form long, thin filaments that move rapidly away from a colony, analogously to swarmer cells in bacteria with flagella. To identify the cause(s) of the hypermotility phenotype, the genome sequences of normal strains and their direct hypermotile derivatives were determined and compared. Strains SM124 and SM127, hypermotile derivatives of strains SM101 and SM102, respectively, contained 10 and 6 single nucleotide polymorphisms (SNPs) relative to their parent strains. While SNPs were located in different genes in the two sets of strains, one feature in common was mutations in cell division genes, an ftsI homolog in strain SM124 (CPR_1831) and a minE homolog in strain SM127 (CPR_2104). Complementation of these mutations with wild-type copies of each gene restored the normal motility phenotype. A model explaining the principles underlying the hypermotility phenotype is presented.

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Carbon Catabolite Repression of Type IV Pilus-Dependent Gliding Motility in the Anaerobic Pathogen Clostridium perfringens

Cited by 47 publications

References 53 publications

CcpA-Dependent Carbohydrate Catabolite Repression Regulates Galactose Metabolism in Streptococcus oligofermentans

CcpA-Dependent Carbohydrate Catabolite Repression Regulates Galactose Metabolism in Streptococcus oligofermentans

Expression of a Clostridium perfringens Type IV Pilin by Neisseria gonorrhoeae Mediates Adherence to Muscle Cells

Hypermotility in Clostridium perfringens Strain SM101 Is Due to Spontaneous Mutations in Genes Linked to Cell Division

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