PilC of <i>Neisseria meningitidis </i>is involved in class II pilus formation and restores pilus assembly, natural transformation competence and adherence to epithelial cells in PilC‐deficient gonococci

Ryll, Roland; Rudel, Thomas; Scheuerpflug, Ina; Barten, Roland; Meyer, Thomas F.

doi:10.1046/j.1365-2958.1997.2631630.x

Cited by 34 publications

(23 citation statements)

References 44 publications

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“…In addition, the lpxA mutant was not naturally competent for DNA transformation. Several components have been implicated as essential for natural transformation in Neisseria, among which are pili, PilT, PilC, ComL, ComP, ComE, and Dca (4,9,38,40,42,51,52). Although most of the studies of DNA transformation have been performed with N. gonorrhoeae, many of the gene products have counterparts in meningococci, with the exception of Dca, which has been found only in gonococcal strains.…”

Section: Discussionmentioning

confidence: 99%

Lipooligosaccharide-DeficientNeisseria meningitidisShows Altered Pilus-Associated Characteristics

2003

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Molecular interaction between host mucosal surfaces and outer membrane components of microbes is crucial in the infection process. The outer membrane of pathogenic Neisseria contains surface molecules such as pili, PilC, and Opa and a monolayer of lipooligosaccharide (LOS), all of which are involved in the interaction with host cells. Pili mediate the initial attachment to human epithelial cells, which is followed by tight contact between bacteria and the eucaryotic cells, leading to bacterial invasion. To further examine the basis for bacterium-host cell contact, we constructed an LOS-deficient Neisseria meningitidis serogroup C mutant. LOS deficiency was without exception accompanied by altered colony opacity and morphology, which most likely represented an "on" switch for Opa540 expression, and by reduced levels of the iron-regulated proteins FetA and FbpA. We show here that LOS is essential for pilus-associated adherence but dispensable for fiber formation and twitching motility. The absence of attachment to epithelial cells could not be attributed to altered levels of piliation or defects in the pilus adhesion phenotype. Further, LOS mutants do not invade host cells and have lost the natural competence for genetic transformation.The mucosal epithelial cell barrier is the first physical defense encountered by bacteria upon contact with the human host. Immediately upon adherence of bacteria, the epithelial cells initiate a nonspecific or innate immune response by production of proinflammatory factors. The inflammatory response to bacterial infections plays an important role in detection and elimination of invading microorganisms. Various components of the bacterial cell wall such as peptidoglycan, lipoteichoic acid, lipoproteins, and lipopolysaccharide (LPS) are capable of activating the proinflammatory reaction. For gram-negative bacteria, LPS is the dominant trigger of the systemic inflammatory response. Recently, Toll-like receptors (TLRs) have been implicated in host responses to bacterial pathogens. Specifically, TLR4 mediates LPS responses whereas TLR2 plays a broader role in the recognition of a variety of bacteria and bacterial antigens (41). The host inflammatory response in meningococcal sepsis is generally believed to be induced by lipooligosaccharide (LOS).LOS of Neisseria meningitidis (meningococcus) is an endotoxin that is structurally distinct from LPS of enteric gramnegative bacteria (21, 33). Unlike most enteric LPSs, meningococcal LOS lacks O-antigen and possesses relatively short polysaccharides, only two to five sugar residues, attached to the meningococcal LOS inner core. LOS is an amphipathic molecule that consists of a hydrophilic carbohydrate portion and a hydrophobic lipid A portion that anchors the LOS to the outer membrane. Endotoxic shock is mediated by the lipid A portion of LOS and is characterized by activation of macrophages and production of a diverse array of cytokines, including those that act as chemoattractants for other leukocytes. Meningococcal septic shock is a direct r...

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Section: Discussionmentioning

confidence: 99%

Lipooligosaccharide-DeficientNeisseria meningitidisShows Altered Pilus-Associated Characteristics

2003

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“…N. gonorrhoeae PilC1 and PilC2 function interchangeably in promoting pilus biogenesis, natural competence, and adherence (39,40). N. meningitidis PilC1 and PilC2 both promote pilus production and natural competence but differentially promote adherence to certain cell types (28,30,41,42). Sequence analysis suggests that differences in PilC1-and PilC2-mediated adherence are based in the N-terminal portion of the proteins (43).…”

Section: Discussionmentioning

confidence: 99%

Calcium Binding Properties of the Kingella kingae PilC1 and PilC2 Proteins Have Differential Effects on Type IV Pilus-Mediated Adherence and Twitching Motility

Porsch

Johnson

Broadnax

et al. 2012

Journal of Bacteriology

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Kingella kingae is an emerging bacterial pathogen that is being recognized increasingly as an important etiology of septic arthritis, osteomyelitis, and bacteremia, especially in young children. The pathogenesis of K. kingae disease begins with bacterial adherence to respiratory epithelium, which is dependent on type IV pili and is influenced by two PilC-like proteins called PilC1 and PilC2. Production of either PilC1 or PilC2 is necessary for K. kingae piliation and bacterial adherence. In this study, we set out to further investigate the role of PilC1 and PilC2 in type IV pilus-associated phenotypes. We found that PilC1 contains a functional 9-amino-acid calcium-binding (Ca-binding) site with homology to the Pseudomonas aeruginosa PilY1 Ca-binding site and that PilC2 contains a functional 12-amino-acid Ca-binding site with homology to the human calmodulin Ca-binding site. Using targeted mutagenesis to disrupt the Ca-binding sites, we demonstrated that the PilC1 and PilC2 Ca-binding sites are dispensable for piliation. Interestingly, we showed that the PilC1 site is necessary for twitching motility and adherence to Chang epithelial cells, while the PilC2 site has only a minor influence on twitching motility and no influence on adherence. These findings establish key differences in PilC1 and PilC2 function in K. kingae and provide insights into the biology of the PilC-like family of proteins.

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“…Both epithelial and endothelial cell interactions with the neisserial type IV pilus seem to follow similar principles and involve identical receptor molecules (27,42). Also, piliated meningococci and gonococci exhibit similar binding specificities, indicating the existence of identical or closely related PilC receptors for both species (41,42). Identifying the neisserial pilus receptor on human cells is therefore of vital importance to our understanding of the basic events taking place during the initial phases of pathogen-host cell contact.…”

Section: Discussionmentioning

confidence: 99%

“…For N. gonorrhoeae it was shown that the two proteins PilC1 and PilC2 have similar functions, i.e., piliation, competence, and adhesion (14,37). In meningococcal strains both PilC proteins are capable of mediating piliation and competence, but only PilC1 promotes adhesion (27,41). Another minor constituent of the pilus fiber, the PilV protein, was shown to be important for type IV pilus-mediated adherence to human epithelial cells (52).…”

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confidence: 99%

CD46-Independent Binding of Neisserial Type IV Pili and the Major Pilus Adhesin, PilC, to Human Epithelial Cells

2005

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Neisseria gonorrhoeae is a gram-negative bacterial pathogen which infects the human mucosal epithelium. An early critical event in neisserial infection is the type IV pilus-mediated adherence to the host cell. The PilC protein, located on the pilus tip, has earlier been identified as the major pilus adhesin. Previous studies suggested that the cell surface protein CD46 is a pilus receptor for Neisseria. We investigated the role of CD46 in pilus-mediated gonococcal infection of epithelial cells. Differences in binding efficiencies of piliated gonococci as well as purified pilus adhesin PilC2 on human epithelial cell lines did not correlate to the level of surface-expressed CD46. Additionally, no binding of piliated gonococci or PilC2 protein was observed on CD46-transfected CHO and MDCK cells. Furthermore, specific down-regulation of CD46 expression in human epithelial cell lines by RNA interference did not alter the binding efficiency of piliated gonococci or purified PilC2 protein, although other CD46-dependent processes, such as measles virus infection and C3b cleavage, were significantly reduced. These data support the notion that pilus-mediated gonococcal infection of epithelial cells can occur in a CD46-independent manner, thus questioning the function of CD46 as an essential pilus receptor for pathogenic neisseriae.

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PilC of Neisseria meningitidis is involved in class II pilus formation and restores pilus assembly, natural transformation competence and adherence to epithelial cells in PilC‐deficient gonococci

Cited by 34 publications

References 44 publications

Lipooligosaccharide-DeficientNeisseria meningitidisShows Altered Pilus-Associated Characteristics

Lipooligosaccharide-DeficientNeisseria meningitidisShows Altered Pilus-Associated Characteristics

Calcium Binding Properties of the Kingella kingae PilC1 and PilC2 Proteins Have Differential Effects on Type IV Pilus-Mediated Adherence and Twitching Motility

CD46-Independent Binding of Neisserial Type IV Pili and the Major Pilus Adhesin, PilC, to Human Epithelial Cells

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