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Weiping Zhang - One of the best experts on this subject based on the ideXlab platform.

  • application of a novel epitope and structure vaccinology assisted fimbria toxin multiepitope fusion antigen of enterotoxigenic escherichia coli for multivalent vaccine development against porcine post weaning diarrhea
    Applied and Environmental Microbiology, 2020
    Co-Authors: Ti Lu, Rodney A Moxley, Weiping Zhang
    Abstract:

    : Enterotoxigenic Escherichia coli (ETEC) strains producing K88 (F4) or F18 Fimbriae and enterotoxins are the predominant cause of pig post-weaning diarrhea (PWD). We recently identified neutralizing epitopes of Fimbriae K88 and F18, heat-labile toxin (LT), heat-stable toxin type I (STa) and type II (STb), and Shiga toxin 2e (Stx2e). In this study, we explored novel epitope- and structure-based vaccinology platform multiepitope-fusion-antigen (MEFA) for PWD vaccine development. By using an epitope-substitution LT toxoid, which lacks enterotoxicity, but retains immunogenicity, as the backbone to present neutralizing epitopes of two ETEC Fimbriae and four toxins, we generated PWD fimbria-toxin MEFA to mimic epitope native antigenicity. We then examined MEFA protein immunogenicity and evaluated MEFA application in PWD vaccine development. Mice subcutaneously immunized with PWD MEFA protein developed strong IgG responses to K88, F18, LT and STb and moderate responses to toxins Stx2e and STa. Importantly, MEFA-induced antibodies inhibited adherence of K88-fimbrial or F18-fimbrial bacteria to pig intestinal cells and also neutralized LT, STa, STb and Stx2e toxicity. These results indicated that PWD fimbria-toxin MEFA induced neutralizing antibodies against unprecedently two Fimbriae and four toxins, and strongly suggested a potential application of this MEFA protein in developing a broadly protective PWD vaccine.IMPORTANCE ETEC associated post-weaning diarrhea (PWD) causes significant economic losses to swine producers worldwide. Currently, there is no effective prevention against PWD. A vaccine that blocks ETEC Fimbriae (K88 and F18) from attaching to host receptors and prevents enterotoxins from stimulating water hypersecretion in pig small intestinal epithelial cells can effectively protect against PWD and significantly improves pig health and well-being. The fimbria-toxin MEFA generated from this study induced neutralizing antibodies against both ETEC Fimbriae and all four ETEC toxins, suggesting a great potential of this fimbria-toxin MEFA in PWD vaccine development and further supporting the general application of this novel MEFA vaccinology platform for multivalent vaccine development.

  • application of a novel epitope and structure based vaccinology assisted fimbria toxin multiepitope fusion antigen of enterotoxigenic escherichia coli for development of multivalent vaccines against porcine postweaning diarrhea
    Applied and Environmental Microbiology, 2020
    Co-Authors: Rodney A Moxley, Weiping Zhang
    Abstract:

    Enterotoxigenic Escherichia coli (ETEC) strains producing K88 (F4) or F18 Fimbriae and enterotoxins are the predominant cause of pig postweaning diarrhea (PWD). We recently identified neutralizing epitopes of Fimbriae K88 and F18, heat-labile toxin (LT), heat-stable toxins type I (STa) and type II (STb), and Shiga toxin 2e (Stx2e). In this study, we explored a novel epitope- and structure-based vaccinology platform, multiepitope fusion antigen (MEFA), for PWD vaccine development. By using an epitope substitution LT toxoid, which lacks enterotoxicity but retains immunogenicity, as the backbone to present neutralizing epitopes of two ETEC Fimbriae and four toxins, we generated PWD fimbria-toxin MEFA to mimic epitope native antigenicity. We then examined MEFA protein immunogenicity and evaluated MEFA application in PWD vaccine development. Mice subcutaneously immunized with PWD MEFA protein developed strong IgG responses to K88, F18, LT, and STb and moderate responses to the toxins Stx2e and STa. Importantly, MEFA-induced antibodies inhibited adherence of K88 or F18 fimbrial bacteria to pig intestinal cells and also neutralized LT, STa, STb, and Stx2e toxicity. These results indicated that PWD fimbria-toxin MEFA induced neutralizing antibodies against an unprecedent two Fimbriae and four toxins and strongly suggested a potential application of this MEFA protein in developing a broadly protective PWD vaccine.IMPORTANCE ETEC-associated postweaning diarrhea (PWD) causes significant economic losses to swine producers worldwide. Currently, there is no effective prevention against PWD. A vaccine that blocks ETEC Fimbriae (K88 and F18) from attaching to host receptors and prevents enterotoxins from stimulating water hypersecretion in pig small intestinal epithelial cells can effectively protect against PWD and significantly improves pig health and well-being. The fimbria-toxin MEFA generated from this study induced neutralizing antibodies against both ETEC Fimbriae and all four ETEC toxins, suggesting a great potential of this fimbria-toxin MEFA in PWD vaccine development and further supporting the general application of this novel MEFA vaccinology platform for multivalent vaccine development.

Harry L. T. Mobley - One of the best experts on this subject based on the ideXlab platform.

  • MrpH, a new class of metal-binding adhesin, requires zinc to mediate biofilm formation.
    'Public Library of Science (PLoS)', 2020
    Co-Authors: Wangshu Jiang, Melanie M Pearson, Harry L. T. Mobley, Wimal Ubhayasekera, Michael C Breed, Allison N Norsworthy, Nina Serr, Stefan D Knight
    Abstract:

    Proteus mirabilis, a Gram-negative uropathogen, is a major causative agent in catheter-associated urinary tract infections (CAUTI). Mannose-resistant Proteus-like Fimbriae (MR/P) are crucially important for P. mirabilis infectivity and are required for biofilm formation and auto-aggregation, as well as for bladder and kidney colonization. Here, the X-ray crystal structure of the MR/P tip adhesin, MrpH, is reported. The structure has a fold not previously described and contains a transition metal center with Zn2+ coordinated by three conserved histidine residues and a ligand. Using biofilm assays, chelation, metal complementation, and site-directed mutagenesis of the three histidines, we show that an intact metal binding site occupied by zinc is essential for MR/P fimbria-mediated biofilm formation, and furthermore, that P. mirabilis biofilm formation is reversible in a zinc-dependent manner. Zinc is also required for MR/P-dependent agglutination of erythrocytes, and mutation of the metal binding site renders P. mirabilis unfit in a mouse model of UTI. The studies presented here provide important clues as to the mechanism of MR/P-mediated biofilm formation and serve as a starting point for identifying the physiological MR/P fimbrial receptor

  • using hemagglutination surface shearing and acid treatment to study Fimbriae in proteus mirabilis
    Methods of Molecular Biology, 2019
    Co-Authors: Stephanie D Himpsl, Melanie M Pearso, Harry L. T. Mobley
    Abstract:

    A critical first step in bacterial virulence and colonization is adherence to mucosal surfaces, often mediated by Fimbriae and other protein adhesins. Here are described three short methods for studying these surface proteins and their behaviors, using protocols developed for the opportunistic pathogen Proteus mirabilis. Unlike the mannose-binding type 1 Fimbriae produced by Escherichia coli, most P. mirabilis strains produce mannose-resistant/Proteus-like (MR/P) Fimbriae. Both types of fimbrial production and adhesion can be easily demonstrated by a simple and economical hemagglutination assay which uses a model system of erythrocytes. The second and third fimbrial methods presented here show how to shear surface-exposed proteins and use acid treatment to separate interlocked fimbrial subunits into monomers.

  • pathogenesis of proteus mirabilis infection
    EcoSal Plus, 2018
    Co-Authors: Chelsie E Armbruster, Harry L. T. Mobley, Melanie M Pearson
    Abstract:

    Proteus mirabilis, a Gram-negative rod-shaped bacterium most noted for its swarming motility and urease activity, frequently causes catheter-associated urinary tract infections (CAUTIs) that are often polymicrobial. These infections may be accompanied by urolithiasis, the development of bladder or kidney stones due to alkalinization of urine from urease-catalyzed urea hydrolysis. Adherence of the bacterium to epithelial and catheter surfaces is mediated by 17 different Fimbriae, most notably MR/P Fimbriae. Repressors of motility are often encoded by these fimbrial operons. Motility is mediated by flagella encoded on a single contiguous 54-kb chromosomal sequence. On agar plates, P. mirabilis undergoes a morphological conversion to a filamentous swarmer cell expressing hundreds of flagella. When swarms from different strains meet, a line of demarcation, a “Dienes line,” develops due to the killing action of each strain’s type VI secretion system. During infection, histological damage is caused by cytotoxins including hemolysin and a variety of proteases, some autotransported. The pathogenesis of infection, including assessment of individual genes or global screens for virulence or fitness factors has been assessed in murine models of ascending urinary tract infections or CAUTIs using both single-species and polymicrobial models. Global gene expression studies performed in culture and in the murine model have revealed the unique metabolism of this bacterium. Vaccines, using MR/P fimbria and its adhesin, MrpH, have been shown to be efficacious in the murine model. A comprehensive review of factors associated with urinary tract infection is presented, encompassing both historical perspectives and current advances.

  • fimbrial profiles predict virulence of uropathogenic escherichia coli strains contribution of ygi and yad Fimbriae
    Infection and Immunity, 2011
    Co-Authors: Rachel R Spurbeck, Ann E Stapleton, James R Johnson, Seth T Walk, Thomas M Hooton, Harry L. T. Mobley
    Abstract:

    Escherichia coli, a cause of ∼90% of urinary tract infections (UTI), utilizes fimbrial adhesins to colonize the uroepithelium. Pyelonephritis isolate E. coli CFT073 carries 12 fimbrial operons, 5 of which have never been studied. Using multiplex PCR, the prevalence of these 12 and 3 additional fimbrial types was determined for a collection of 303 E. coli isolates (57 human commensal, 32 animal commensal, 54 asymptomatic bacteriuria, 45 complicated UTI, 38 uncomplicated cystitis, and 77 pyelonephritis). The number of fimbrial types per E. coli isolate was distributed bimodally: those with low (3.2 ± 1.1) and those with high (8.3 ± 1.3) numbers of fimbrial types (means ± standard errors of the means). The fimbrial genes ygiL, yadN, yfcV, and c2395 were significantly more prevalent among urine isolates than human commensal isolates. The effect of deletion of Ygi and Yad fimbrial operons on growth, motility, biofilm formation, adherence to immortalized human epithelial cells, and pathogenesis in the mouse model of UTI was examined. Yad Fimbriae were necessary for wild-type levels of adherence to a bladder epithelial cell line and for biofilm formation. Deletion of these fimbrial genes increased motility. Ygi Fimbriae were necessary for wild-type levels of adherence to a human embryonic kidney cell line, biofilm formation, and in vivo fitness in the urine and kidneys. Complementation of each fimbrial mutant restored wild-type levels of motility, biofilm formation, adherence and, for ygi, in vivo fitness. A double deletion strain, Δygi Δyad, was attenuated in the urine, bladder, and kidneys in the mouse model, demonstrating that these Fimbriae contribute to uropathogenesis.

  • oxygen limiting conditions enrich for fimbriate cells of uropathogenic proteus mirabilis and escherichia coli
    Journal of Bacteriology, 2009
    Co-Authors: Chelsea M Lane, Melanie M Pearso, Amy N Simms, Harry L. T. Mobley
    Abstract:

    MR/P Fimbriae of uropathogenic Proteus mirabilis undergo invertible element-mediated phase variation whereby an individual bacterium switches between expressing Fimbriae (phase ON) and not expressing Fimbriae (phase OFF). Under different conditions, the percentage of fimbriate bacteria within a population varies and could be dictated by either selection (growth advantage of one phase) or signaling (preferentially converting one phase to the other in response to external signals). Expression of MR/P Fimbriae increases in a cell-density dependent manner in vitro and in vivo. However, rather than the increased cell density itself, this increase in fimbrial expression is due to an enrichment of fimbriate bacteria under oxygen limitation resulting from increased cell density. Our data also indicate that the persistence of MR/P fimbriate bacteria under oxygen-limiting conditions is a result of both selection (of MR/P fimbrial phase variants) and signaling (via modulation of expression of the MrpI recombinase). Furthermore, the mrpJ transcriptional regulator encoded within the mrp operon contributes to phase switching. Type 1 Fimbriae of Escherichia coli, which are likewise subject to phase variation via an invertible element, also increase in expression during reduced oxygenation. These findings provide evidence to support a mechanism for persistence of fimbriate bacteria under oxygen limitation, which is relevant to disease progression within the oxygen-restricted urinary tract.

Geula Klorin - One of the best experts on this subject based on the ideXlab platform.

  • can morphometric analysis of the fallopian tube fimbria predict the presence of uterine papillary serous carcinoma upsc
    PLOS ONE, 2019
    Co-Authors: Amnon Amit, Edmond Sabo, Avielle Movsas, Yamit Efrat Tamam, Ari Reiss, Emad Matanes, Geula Klorin
    Abstract:

    : Uterine serous papillary carcinoma (UPSC) is an aggressive tumor, often diagnosed as a metastatic disease and characterized by a high recurrence rate and poor prognosis. UPSC represents a distinct subtype of endometrial cancer which is different in clinical and pathological behaviors from endometrioid endometrial carcinoma (EEC) and resembles more to serous ovarian carcinoma. Since tumors of serous papillary of the ovary are hypothesized to stem from cells of the fallopian tube's fimbria, we hypothesized that UPSC may also origin in the fallopian tubes. In our previous study, using a novel method of computerized morphometry of the fimbrial epithelium we have found significant differences between Fimbriae of healthy women and serous ovarian cancer patients. In this study we showed the presence of morphologic differences between twenty-four Fimbriae from healthy women, and twenty six Fimbriae from uterus cancer (13 from UPSC patients and 13 from EEC patients). All Fimbriae reported by the pathologist as "normal" were subjected to a computerized histomorphometric analysis. Two-step method of computerized histomorphometry, i.e. Fast Fourier transformation (FFT) followed by a co-occurrence matrix analysis and an additional analysis of the nuclear symmetry of the tubal fimbrial epithelium were applied. Using these novel methods, we were able to show differences in the morphometric characteristics of the Fimbriae in UPSC patients compared to EEC and healthy patients. It is yet to be determined the clinical significance of this observation.

  • can morphometric analysis of the fallopian tube fimbria predict the presence of uterine papillary serous carcinoma upsc
    PLOS ONE, 2019
    Co-Authors: Amnon Amit, Edmond Sabo, Avielle Movsas, Yamit Efrat Tamam, Ari Reiss, Emad Matanes, Geula Klorin
    Abstract:

    : Uterine serous papillary carcinoma (UPSC) is an aggressive tumor, often diagnosed as a metastatic disease and characterized by a high recurrence rate and poor prognosis. UPSC represents a distinct subtype of endometrial cancer which is different in clinical and pathological behaviors from endometrioid endometrial carcinoma (EEC) and resembles more to serous ovarian carcinoma. Since tumors of serous papillary of the ovary are hypothesized to stem from cells of the fallopian tube's fimbria, we hypothesized that UPSC may also origin in the fallopian tubes. In our previous study, using a novel method of computerized morphometry of the fimbrial epithelium we have found significant differences between Fimbriae of healthy women and serous ovarian cancer patients. In this study we showed the presence of morphologic differences between twenty-four Fimbriae from healthy women, and twenty six Fimbriae from uterus cancer (13 from UPSC patients and 13 from EEC patients). All Fimbriae reported by the pathologist as "normal" were subjected to a computerized histomorphometric analysis. Two-step method of computerized histomorphometry, i.e. Fast Fourier transformation (FFT) followed by a co-occurrence matrix analysis and an additional analysis of the nuclear symmetry of the tubal fimbrial epithelium were applied. Using these novel methods, we were able to show differences in the morphometric characteristics of the Fimbriae in UPSC patients compared to EEC and healthy patients. It is yet to be determined the clinical significance of this observation.

  • evaluation of microscopic changes in fallopian tubes of brca mutation carriers by morphometric analysis of histologic slides a preliminary pilot study
    International Journal of Gynecological Pathology, 2017
    Co-Authors: Amnon Amit, Edmond Sabo, Ari Reiss, Emad Matanes, Einat Trugman, Irena Pranovich, Yaniv Zohar, Geula Klorin
    Abstract:

    : Mutations in BRCA genes increase the risk of ovarian cancer, yet no method for early diagnosis is available. Some serous ovarian tumors are hypothesized to stem from cells of the fallopian tube fimbria. Using a novel method of computerized morphometry of the fimbrial epithelium, this study aimed to detect morphologic differences in noncancerous Fimbriae between BRCA mutation carriers and noncarriers, and between healthy and serous ovarian cancer patients. Twenty-four Fimbriae from healthy women (13 BRCA+, 11 BRCA-) and 21 Fimbriae from women with serous ovarian cancer (10 BRCA+, 11 BRCA-), all reported as "normal" by hematoxylin and eosin examination, were subjected to computerized histomorphometric analysis. A Fast Fourier Transformation was applied to images of fimbrial epithelium and the Fast Fourier Transformation 2-dimensional frequency maps were subsequently quantified for nuclear orientation and planar distribution by a cooccurrence matrix analysis. Additional analysis of nuclear contour was applied to the Fimbriae of the healthy women. Among the healthy women, significant differences were found in morphometric characteristics between the BRCA mutation carriers and noncarriers. Among the women with ovarian cancer, no significant differences were found between BRCA mutation carriers and noncarriers. Between healthy women and those with ovarian cancer, significant differences were detected, regardless of BRCA mutational status. A novel method, which combined Fast Fourier Transformation with cooccurrence matrix analysis, demonstrated differences in morphometric characteristics in the Fimbriae between healthy and ovarian cancer patients, and between BRCA mutation carriers and noncarriers. The clinical significance of these observations should be investigated.

Karen Angeliki Krogfelt - One of the best experts on this subject based on the ideXlab platform.

  • 2009. Identification of a conserved chromosomal region encoding Klebsiella pneumoniae type 1 and type 3 Fimbriae and assessment of the role of Fimbriae in pathogenicity. Infect. Immun
    2016
    Co-Authors: Carsten Struve, Martin Bojer, Karen Angeliki Krogfelt
    Abstract:

    Type 3 Fimbriae are expressed by most clinical Klebsiella pneumoniae isolates and mediate adhesion to host structures in vitro. However, the role of type 3 Fimbriae in K. pneumoniae virulence has not been evaluated by use of in vivo infection models. In this study, the type 3 fimbrial gene cluster (mrk) of the clinical isolate C3091 is described in detail. The mrk gene cluster was revealed to be localized in close proximity to the type 1 fimbrial gene cluster. Thus, a 20.4-kb fimbria-encoding region was identified and found to be highly conserved among different K. pneumoniae isolates. Interestingly, a homologue to PecS, known as a global regulator of virulence in Erwinia chrysanthemi, was identified in the fimbria-encoding region. Comparison to the previously characterized plasmid encodedmrk gene cluster revealed significant differences, and it is established here that the putative regulatory gene mrkE is not a part of the chromosomally encoded type 3 fimbrial gene cluster. To evaluate the role of type 3 Fimbriae in virulence, a type 3 fimbria mutant and a type 1 and type 3 fimbria double mutant was constructed. Type 3 fimbria expression was found to strongly promote biofilm formation. However, the fimbria mutants were as effective at colonizing the intestine as the wild type, and their virulence was not attenuated in a lung infection model. Also, in a urinary tract infection model, type 3 Fimbriae did not influence the virulence, whereas type 1 Fimbriae were verified as an essential virulence factor. Thus, type 3 Fimbriae were established not to be a virulence factor in uncomplicated K. pneumoniae infections. However, since type 3 Fimbriae promote biofilm formation, their role in development o

  • characterization of klebsiella pneumoniae type 1 Fimbriae by detection of phase variation during colonization and infection and impact on virulence
    Infection and Immunity, 2008
    Co-Authors: Carsten Struve, Martin Saxtorph Bojer, Karen Angeliki Krogfelt
    Abstract:

    Klebsiella pneumoniae is recognized as an important gram-negative opportunistic pathogen. The ability of bacteria to adhere to host structures is considered essential for the development of infections; however, few studies have examined the influence of adhesion factors on K. pneumoniae virulence. In this study, we cloned and characterized the type 1 fimbria gene cluster of a clinical K. pneumoniae isolate. Although this cluster was not identical to the Escherichia coli type 1 fimbria gene cluster, an overall high degree of structural resemblance was demonstrated. Unique to the K. pneumoniae fim gene cluster is the fimK gene, whose product contains an EAL domain, suggesting that it has a role in regulation of fimbrial expression. Like expression of type 1 Fimbriae in E. coli, expression of type 1 Fimbriae in K. pneumoniae was found to be phase variable, and an invertible DNA element (fim switch) was characterized. An isogenic type 1 fimbria mutant was constructed and used to evaluate the influence of type 1 Fimbriae in different infection models. Type 1 Fimbriae did not influence the ability of K. pneumoniae to colonize the intestine or infect the lungs, but they were determined to be a significant virulence factor in K. pneumoniae urinary tract infection. By use of a PCR-based assay, the orientation of the fim switch during colonization and infection was investigated and was found to be all “off” in the intestine and lungs but all “on” in the urinary tract. Our results suggest that during colonization and infection, there is pronounced selective pressure in different host environments for selection of either the type 1 fimbriated or nonfimbriated phenotype of K. pneumoniae.

  • capsule and fimbria interaction in klebsiella pneumoniae
    Infection and Immunity, 2005
    Co-Authors: Mark A Schembri, Jens Blom, Karen Angeliki Krogfelt, Per Klemm
    Abstract:

    The capsular polysaccharide and type I Fimbriae are two of the major surface-located virulence properties associated with the pathogenesis of Klebsiella pneumoniae. The capsule is an elaborate polysaccharide matrix that encases the entire cell surface and provides resistance against many host defense mechanisms. In contrast, type 1 Fimbriae are thin adhesive thread-like surface organelles that can extend beyond the capsular matrix and mediate D-mannose-sensitive adhesion to host epithelial cells. These Fimbriae are archetypical and consist of a major building block protein (FimA) that comprises the bulk of the organelle and a tip-located adhesin (FimH). It is assumed that the extended major-subunit protein structure permits the FimH adhesin to function independently of the presence of a capsule. In this study, we have employed a defined set of K. pneumoniae capsulated and noncapsulated strains to show that the function of type I Fimbriae is actually impeded by the concomitant expression of a polysaccharide capsule. Capsule expression had significant effects on two parameters commonly used to define FimH function, namely, yeast cell agglutination and biofilm formation. Our data suggest that this effect is not due to transcriptional/translational changes in fimbrial gene/protein expression but rather the result of direct physical interference. This was further demonstrated by the fact that we could restore fimbrial function by inhibiting capsule synthesis. It remains to be determined whether the expression of these very different surface components occurs simply via random events of phase variation or in a coordinated manner in response to specific environmental cues.

John S Mattick - One of the best experts on this subject based on the ideXlab platform.

  • identification of a gene pilf required for type 4 fimbrial biogenesis and twitching motility in pseudomonas aeruginosa
    Gene, 1996
    Co-Authors: Alison A Watson, Richard A Alm, John S Mattick
    Abstract:

    Many bacterial pathogens produce a class of surface structures called type 4 Fimbriae. In Pseudomonas aeruginosa these Fimbriae are responsible for adhesion and translocation across host epithelial surfaces. We have identified a novel gene involved in the complex process of type 4 fimbrial biogenesis. This gene, termed pilF, is located on SpeI fragment S at 30 min on the P. aeruginosa genomic map, which is the sixth region on the chromosome shown to contain a fimbrial-associated gene. The PilF protein has a predicted M(r) of 22402, and together with a highly homologous upstream ORF shares a chromosomal arrangement similar to that found in Haemophilus influenzae. A pilF mutant is blocked in the export/assembly of the fimbrial subunit PilA, and accumulates this protein in the membrane fraction. Complementation studies indicate that the cloned pilF gene is able to restore the expression of surface Fimbriae, twitching motility and susceptibility to fimbrial-specific bacteriophage.

  • identification of a gene pilv required for type 4 fimbrial biogenesis in pseudomonas aeruginosa whose product possesses a pre pilin like leader sequence
    Molecular Microbiology, 1995
    Co-Authors: Richard A Alm, John S Mattick
    Abstract:

    Type 4 Fimbriae are important colonization factors in Pseudomonas aeruginosa and other pathogens that mediate attachment to epithelial cells of the host. They are also responsible for a form of translocation termed 'twitching motility' and are implicated in the susceptibility to fimbrial-specific bacteriophage. Analysis of a transposon mutant which lacks functional Fimbriae has identified a new gene which is required for fimbrial biogenesis. This gene, termed pilV, is located on chromosomal SpeI fragment E, 2 kb downstream of the previously characterized pilSR genes involved in transcriptional activation of the fimbrial subunit gene. The pilV gene encodes a 20 kDa membrane-located protein with considerable amino-terminal homology to the type 4 consensus pre-pilin leader sequence, suggesting that it is processed by a leader peptidase. Site-directed mutagenesis has shown that PilV requires such cleavage to be functional. PilV also exhibits close similarity to a group of proteins involved in extracellular protein secretion from a number of Gram-negative bacteria, suggesting that the biogenesis of type 4 Fimbriae may have a similar basis.

  • common components in the assembly of type 4 Fimbriae dna transfer systems filamentous phage and protein secretion apparatus a general system for the formation of surface associated protein complexes
    Molecular Microbiology, 1993
    Co-Authors: Matthew Hobbs, John S Mattick
    Abstract:

    The Pseudomonas aeruginosa genes pilB‐D and pilQ are necessary for the assembly of type 4 Fimbriae. Homologues of these genes and of the subunit (pilin) gene have been described in various different bacterial species, but not always in association with type 4 fimbrial biosynthesis and function. Pil‐like proteins are also involved in protein secretion, DNA transfer by conjugation and transformation, and morphogenesis of filamentous bacteriophages. It seems likely that the Pil homologues function in the processing and export of proteins resembling type 4 fimbrial sub‐units, and in their organization into fimbrial‐like structures. These may either be true type 4 Fimbriae, or components of protein complexes which act in the transport of macromolecules (DNA or protein) into or out of the cell. Some PilB‐like and PilQ‐like proteins are apparently also involved in the assembly of non‐type 4 polymeric structures (filamentous phage virions and conjugative pili). The diverse studies summarized in this review are providing insight into an extensive infrastructural system which appears to be utilized in the formation of a variety of cell surface‐associated complexes.