Sortase-Catalyzed Assembly of Distinct Heteromeric Fimbriae in Actinomyces naeslundii

ABSTRACT Two types of adhesive fimbriae are expressed by Actinomyces; however, the architecture and the mechanism of assembly of these structures remain poorly understood. In this study we characterized two fimbrial gene clusters present in the genome of Actinomyces naeslundii strain MG-1. By using immunoelectron microscopy and biochemical analysis, we showed that the fimQ-fimP-srtC1-fimR gene cluster encodes a fimbrial structure (designated type 1) that contains a major subunit, FimP, forming the shaft and a minor subunit, FimQ, located primarily at the tip. Similarly, the fimB-fimA-srtC2 gene cluster encodes a distinct fimbrial structure (designated type 2) composed of a shaft protein, FimA, and a tip protein, FimB. By using allelic exchange, we constructed an in-frame deletion mutant that lacks the SrtC2 sortase. This mutant produces abundant type 1 fimbriae and expresses the monomeric FimA and FimB proteins, but it does not assemble type 2 fimbriae. Thus, SrtC2 is a fimbria-specific sortase that is essential for assembly of the type 2 fimbriae. Together, our experiments pave the way for several lines of molecular investigation that are necessary to elucidate the fimbrial assembly pathways in Actinomyces and their function in the pathogenesis of different biofilm-related oral diseases.

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Antigenic and Biochemical Analysis of gB of Herpes Simplex Virus Type 1 and Type 2 and of Cross-reacting Glycoproteins Induced by Bovine Mammillitis Virus and Equine Herpesvirus Type 1

Journal of General Virology ◽

10.1099/0022-1317-66-2-231 ◽

1985 ◽

Vol 66 (2) ◽

pp. 231-247 ◽

Cited By ~ 25

Author(s):

B. W. Snowden ◽

P. R. Kinchington ◽

K. L. Powell ◽

I. W. Halliburton

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Herpes Simplex Virus Type ◽

Biochemical Analysis ◽

Equine Herpesvirus ◽

Herpesvirus Type ◽

Equine Herpesvirus Type 1 ◽

Simplex Virus

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Conservation of a gene cluster including glycoprotein B in bovine herpesvirus type 2 (BHV-2) and herpes simplex virus type 1 (HSV-1)

Virology ◽

10.1016/0042-6822(88)90583-1 ◽

1988 ◽

Vol 165 (2) ◽

pp. 388-405 ◽

Cited By ~ 26

Author(s):

Wolfgang Hammerschmidt ◽

Franz Conraths ◽

Joachim Mankertzt ◽

Georg Pauli ◽

Hanns Ludwig ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Gene Cluster ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Bovine Herpesvirus ◽

Herpesvirus Type ◽

Simplex Virus

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Genotypes of JC virus in East, Central and Southwest Europe

Journal of General Virology ◽

10.1099/0022-1317-82-5-1221 ◽

2001 ◽

Vol 82 (5) ◽

pp. 1221-1331 ◽

Cited By ~ 67

Author(s):

Hansjürgen T. Agostini ◽

Alison Deckhut ◽

David V. Jobes ◽

Rosina Girones ◽

Günther Schlunck ◽

...

Keyword(s):

Jc Virus ◽

Regulatory Region ◽

Phylogenetic Reconstruction ◽

Asian Population ◽

Entire Genome ◽

East Central ◽

European Americans ◽

A Minor

Distinctive genotypes of JC virus have been described for the major continental landmasses. Studies on European-Americans and small cohorts in Europe showed predominantly Type 1. Types 2 and 7 are found in Asia, and Types 3 and 6 in Africa. These genotypes differ in sequence by about 1–3%. Each genotype may have several subtypes which differ from each other by about 0·5–1%. The genotypes can be defined by a distinctive pattern of nucleotides in a typing region of the VP1 gene. This genotyping approach has been confirmed by phylogenetic reconstruction using the entire genome exclusive of the rearranging regulatory region. In this first large European study, we report on the urinary excretion of JCV DNA of 350 individuals from Poland, Hungary, Germany and Spain. We included Gypsy cohorts in Hungary (Roma), Germany (Sinti), and Spain (Gitano), as well as Basques in Spain. We show that while Type 1 predominates in Europe, the proportions of Type 1A and 1B may differ from East to Southwest Europe. Type 4, closely related to the Type 1 sequence (only ∼1% difference) was a minor genotype in Germany, Poland and Spain, but represented the majority in Basques. The Gitanos in Spain showed a variant Type 4 sequence termed ‘Rom-1’. Interestingly, neither the Gitanos in Spain, nor Sinti or Roma in Germany or Hungary showed the Type 2 or Type 7 genotype that might be expected if their origins were in an Asian population.

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Type III Pilus of Corynebacteria: Pilus Length Is Determined by the Level of Its Major Pilin Subunit

Journal of Bacteriology ◽

10.1128/jb.00606-06 ◽

2006 ◽

Vol 188 (17) ◽

pp. 6318-6325 ◽

Cited By ~ 54

Author(s):

Arlene Swierczynski ◽

Hung Ton-That

Keyword(s):

Gene Cluster ◽

Biochemical Analysis ◽

Gene Clusters ◽

Inducible Promoter ◽

The Other ◽

Bacterial Genomes ◽

Gram Positive ◽

The Third ◽

Pilin Subunit

ABSTRACT Multiple pilus gene clusters have been identified in several gram-positive bacterial genomes sequenced to date, including the Actinomycetales, clostridia, streptococci, and corynebacteria. The genome of Corynebacterium diphtheriae contains three pilus gene clusters, two of which have been previously characterized. Here, we report the characterization of the third pilus encoded by the spaHIG cluster. By using electron microscopy and biochemical analysis, we demonstrate that SpaH forms the pilus shaft, while SpaI decorates the structure and SpaG is largely located at the pilus tip. The assembly of the SpaHIG pilus requires a specific sortase located within the spaHIG pilus gene cluster. Deletion of genes specific for the synthesis and polymerization of the other two pilus types does not affect the SpaHIG pilus. Moreover, SpaH but not SpaI or SpaG is essential for the formation of the filament. When expressed under the control of an inducible promoter, the amount of the SpaH pilin regulates pilus length; no pili are assembled from an SpaH precursor that has an alanine in place of the conserved lysine of the SpaH pilin motif. Thus, the spaHIG pilus gene cluster encodes a pilus structure that is independently assembled and antigenically distinct from other pili of C. diphtheriae. We incorporate these findings in a model of sortase-mediated pilus assembly that may be applicable to many gram-positive pathogens.

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Emerging Treatment Strategies for Diabetes Mellitus and Associated Complications: An Update

Pharmaceutics ◽

10.3390/pharmaceutics13101568 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1568

Author(s):

Vijay Mishra ◽

Pallavi Nayak ◽

Mayank Sharma ◽

Aqel Albutti ◽

Ameen S. S. Alwashmi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Treatment Strategies ◽

High Blood Glucose ◽

The Status ◽

Minor Disease ◽

A Minor ◽

Oral Hypoglycemic Drugs

The occurrence of diabetes mellitus (DM) is increasing rapidly at an accelerating rate worldwide. The status of diabetes has changed over the last three generations; whereas before it was deemed a minor disease of older people but currently it is now one of the leading causes of morbidity and mortality among middle-aged and young people. High blood glucose-mediated functional loss, insulin sensitivity, and insulin deficiency lead to chronic disorders such as Type 1 and Type 2 DM. Traditional treatments of DM, such as insulin sensitization and insulin secretion cause undesirable side effects, leading to patient incompliance and lack of treatment. Nanotechnology in diabetes studies has encouraged the development of new modalities for measuring glucose and supplying insulin that hold the potential to improve the quality of life of diabetics. Other therapies, such as β-cells regeneration and gene therapy, in addition to insulin and oral hypoglycemic drugs, are currently used to control diabetes. The present review highlights the nanocarrier-based drug delivery systems and emerging treatment strategies of DM.

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Amended Description of the Genes for Synthesis of Actinomyces naeslundii T14V Type 1 Fimbriae and Associated Adhesin

Infection and Immunity ◽

10.1128/iai.01955-06 ◽

2007 ◽

Vol 75 (8) ◽

pp. 4181-4185 ◽

Cited By ~ 11

Author(s):

Ping Chen ◽

John O. Cisar ◽

Sonja Hess ◽

Jenny T. C. Ho ◽

Kai P. Leung

Keyword(s):

Tooth Surface ◽

Gram Positive ◽

Type 1 Fimbriae ◽

Actinomyces Naeslundii ◽

Fimbrial Subunit ◽

Structural Subunit ◽

A Minor

ABSTRACT The type 1 fimbriae of Actinomyces naeslundii T14V mediate adhesion of this gram-positive species to the tooth surface. The present findings show that the locus for type 1 fimbria production in this strain includes three genes, fimQ for a minor fimbrial subunit that appears to be an adhesin, fimP for the major structural subunit, and srtC1 for a type 1 fimbria-specific sortase involved in the assembly of these structures.

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Antigenic and Biochemical Analysis of gB of Herpes Simplex Virus Type 1 and Type 2 and of Cross-reacting Glycoproteins Induced by Bovine Mammillitis Virus and Equine Herpesvirus Type 1

Journal of General Virology ◽

10.1099/0022-1317-66-9-2077 ◽

1985 ◽

Vol 66 (9) ◽

pp. 2077-2077

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Herpes Simplex Virus Type ◽

Biochemical Analysis ◽

Equine Herpesvirus ◽

Herpesvirus Type ◽

Equine Herpesvirus Type 1 ◽

Simplex Virus

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Actinomyces naeslundii Displays VariantfimP and fimA Fimbrial Subunit Genes Corresponding to Different Types of Acidic Proline-Rich Protein and β-Linked Galactosamine Binding Specificity

Infection and Immunity ◽

10.1128/iai.66.9.4403-4410.1998 ◽

1998 ◽

Vol 66 (9) ◽

pp. 4403-4410 ◽

Cited By ~ 20

Author(s):

K. Hallberg ◽

C. Holm ◽

U. Öhman ◽

N. Strömberg

Keyword(s):

Molecular Basis ◽

Binding Specificity ◽

Actinomyces Naeslundii ◽

Fimbrial Subunit ◽

Streptococcus Oralis ◽

Binding Preference ◽

Different Types ◽

Preferential Binding

ABSTRACT Actinomyces naeslundii genospecies 1 and 2 bind to acidic proline-rich proteins (APRPs) and statherin via type 1 fimbriae and to β-linked galactosamine (GalNAcβ) structures via type 2 fimbriae. In addition, A. naeslundii displays two types of binding specificity for both APRPs-statherin and GalNAcβ, while Actinomyces odontolyticusbinds to unknown structures. To study the molecular basis for these binding specificities, DNA fragments spanning the entire or central portions of fimP (type 1) and fimA (type 2) fimbrial subunit genes were amplified by PCR from strains of genospecies 1 and 2 and hybridized with DNA from two independent collections of oral Actinomyces isolates. Isolates of genospecies 1 and 2 and A. odontolyticus, but no otherActinomyces species, were positive for hybridization withfimP and fimA full-length probes irrespective of binding to APRPs and statherin, GalNAcβ, or unknown structures. Isolates of genospecies 1 and 2, with deviating patterns of GalNAcβ1-3Galα-O-ethyl-inhibitable coaggregation with Streptococcus oralis Ss34 and MPB1, were distinguished by a fimA central probe from genospecies 1 and 2, respectively. Furthermore, isolates of genospecies 1 and 2 displaying preferential binding to APRPs over statherin were positive with a fimP central probe, while a genospecies 2 strain with the opposite binding preference was not. The sequences offimP and fimA central gene segments were highly conserved among isolates with the same, but diversified between those with a variant, binding specificity. In conclusion, A. naeslundii exhibits variant fimP andfimA genes corresponding to diverse APRP and GalNAcβ specificities, respectively, while A. odontolyticus has a genetically related but distinct adhesin binding specificity.

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