scholarly journals Discovery of Fibrillar Adhesins across Bacterial Species

2020 ◽  
Author(s):  
Vivian Monzon ◽  
Aleix Lafita ◽  
Alex Bateman
Keyword(s):  
Cell Surface ◽  
Bacterial Species ◽  
Domain Architecture ◽  
Surface Proteins ◽  
Host Cells ◽  
Bacterial Surface ◽  
Bacterial Phyla ◽  
C Terminus ◽  
Wide Range ◽  
Bacterial Proteomes

AbstractBackgroundFibrillar adhesins are long multidomain proteins attached at the cell surface and composed of at least one adhesive domain and multiple tandemly repeated domains, which build an elongated stalk that projects the adhesive domain beyond the bacterial cell surface. They are an important yet understudied class of proteins that mediate interactions of bacteria with their environment. This study aims to characterize fibrillar adhesins in a wide range of bacterial phyla and to identify new fibrillar adhesin-like proteins to improve our understanding of host-bacteria interactions.ResultsBy careful search for fibrillar adhesins in the literature and by computational analysis we identified 75 stalk domains and 24 adhesive domains. Based on the presence of these domains in the UniProt Reference Proteomes database, we identified and analysed 3,388 fibrillar adhesin-like proteins across species of the most common bacterial phyla. We found that the bacterial proteomes with the highest fraction of fibrillar adhesins include several known pathogens. We further enumerate the adhesive and stalk domain combinations found in nature and demonstrate that fibrillar adhesins have complex and variable domain architectures, which differ across species. By analysing the domain architecture of fibrillar adhesins we show that in Gram positive bacteria adhesive domains are mostly positioned at the N-terminus of the protein with the cell surface anchor at the C-terminus, while their positions are more variable in Gram negative bacteria. We provide an open repository of fibrillar adhesin-like proteins and domains to facilitate downstream studies of this class of bacterial surface proteins.ConclusionThis study provides a domain-based characterization of fibrillar adhesins and demonstrates that they are widely found across the main bacterial phyla. We have discovered numerous novel fibrillar adhesins and improved the understanding of how pathogens might adhere to and subsequently invade into host cells.

scholarly journals Discovery of fibrillar adhesins across bacterial species

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Vivian Monzon ◽  
Aleix Lafita ◽  
Alex Bateman
Keyword(s):  
Cell Surface ◽  
Bacterial Species ◽  
Domain Architecture ◽  
Surface Proteins ◽  
Bacterial Surface ◽  
Bacterial Phyla ◽  
Gram Positive Bacteria ◽  
Invasion Mechanisms ◽  
C Terminus ◽  
Wide Range

Abstract Background Fibrillar adhesins are long multidomain proteins that form filamentous structures at the cell surface of bacteria. They are an important yet understudied class of proteins composed of adhesive and stalk domains that mediate interactions of bacteria with their environment. This study aims to characterize fibrillar adhesins in a wide range of bacterial phyla and to identify new fibrillar adhesin-like proteins to improve our understanding of host-bacteria interactions. Results Through careful literature and computational searches, we identified 82 stalk and 27 adhesive domain families in fibrillar adhesins. Based on the presence of these domains in the UniProt Reference Proteomes database, we identified and analysed 3,542 fibrillar adhesin-like proteins across species of the most common bacterial phyla. We further enumerate the adhesive and stalk domain combinations found in nature and demonstrate that fibrillar adhesins have complex and variable domain architectures, which differ across species. By analysing the domain architecture of fibrillar adhesins, we show that in Gram positive bacteria, adhesive domains are mostly positioned at the N-terminus and cell surface anchors at the C-terminus of the protein, while their positions are more variable in Gram negative bacteria. We provide an open repository of fibrillar adhesin-like proteins and domains to enable further studies of this class of bacterial surface proteins. Conclusion This study provides a domain-based characterization of fibrillar adhesins and demonstrates that they are widely found in species across the main bacterial phyla. We have discovered numerous novel fibrillar adhesins and improved our understanding of pathogenic adhesion and invasion mechanisms.

scholarly journals Legionella pneumophila DotU and IcmF Are Required for Stability of the Dot/Icm Complex

2004 ◽  
Vol 72 (10) ◽  
pp. 5983-5992 ◽  
Author(s):  
Jessica A. Sexton ◽  
Jennifer L. Miller ◽  
Aki Yoneda ◽  
Thomas E. Kehl-Fie ◽  
Joseph P. Vogel
Keyword(s):  
Cell Surface ◽  
Legionella Pneumophila ◽  
Bacterial Species ◽  
Wide Distribution ◽  
Host Cells ◽  
Growth Defect ◽  
Intracellular Growth ◽  
Homologous Proteins ◽  
Type Iv ◽  
Cell Surface Structure

ABSTRACT Legionella pneumophila utilizes a type IV secretion system (T4SS) encoded by 26 dot/icm genes to replicate inside host cells and cause disease. In contrast to all other L. pneumophila dot/icm genes, dotU and icmF have homologs in a wide variety of gram-negative bacteria, none of which possess a T4SS. Instead, dotU and icmF orthologs are linked to a locus encoding a conserved cluster of proteins designated IcmF-associated homologous proteins, which has been proposed to constitute a novel cell surface structure. We show here that dotU is partially required for L. pneumophila intracellular growth, similar to the known requirement for icmF. In addition, we show that dotU and icmF are necessary for optimal plasmid transfer and sodium sensitivity, two additional phenotypes associated with a functional Dot/Icm complex. We found that these effects are due to the destabilization of the T4SS at the transition into the stationary phase, the point at which L. pneumophila becomes virulent. Specifically, three Dot proteins (DotH, DotG, and DotF) exhibit decreased stability in a ΔdotU ΔicmF strain. Furthermore, overexpression of just one of these proteins, DotH, is sufficient to suppress the intracellular growth defect of the ΔdotU ΔicmF mutant. This suggests a model where the DotU and IcmF proteins serve to prevent DotH degradation and therefore function to stabilize the L. pneumophila T4SS. Due to their wide distribution among bacterial species and their genetic linkage to known or predicted cell surface structures, we propose that this function in complex stabilization may be broadly conserved.

scholarly journals Invasion mechanisms of Gram-positive pathogenic cocci

2007 ◽  
Vol 98 (09) ◽  
pp. 488-496 ◽  
Author(s):  
Patric Nitsche-Schmitz ◽  
Manfred Rohde ◽  
Gursharan Chhatwal
Keyword(s):  
Surface Proteins ◽  
Host Cells ◽  
Human Pathogens ◽  
Gram Positive ◽  
Bacterial Surface ◽  
Surface Receptors ◽  
Major Threat ◽  
Invasion Mechanisms ◽  
Invasive Infections ◽  
Gram Positive Cocci

SummaryGram-positive cocci are important human pathogens. Streptococci and staphylococci in particular are a major threat to human health,since they cause a variety of serious invasive infections. Their invasion into normally sterile sites of the host depends on elaborated bacterial mechanisms that involve adhesion to the host tissue, its degradation, internalisation by host cells, and passage through epithelia and endothelia. Interactions of bacterial surface proteins with proteins of the host’s extracellular matrix as well as with cell surface receptors are crucial factors in these processes, and some of the key mechanisms are similar in many pathogenic Gram-positive cocci.Therapies that interfere with these mechanisms may become efficient alternatives to today’s antibiotic treatments.

scholarly journals Topology, Antiviral Functional Residues and Mechanism of IFITM1

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 295
Author(s):  
Fang Sun ◽  
Zhiqiang Xia ◽  
Yuewen Han ◽  
Minjun Gao ◽  
Luyao Wang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Dengue Virus ◽  
Zika Virus ◽  
Transmembrane Proteins ◽  
Host Cells ◽  
Intracellular Loop ◽  
C Terminus ◽  
Wide Range ◽  
N Terminus

Interferon-inducible transmembrane proteins (IFITM1/2/3) have been reported to suppress the entry of a wide range of viruses. However, their antiviral functional residues and specific mechanisms are still unclear. Here, we firstly resolved the topology of IFITM1 on the plasma membrane where N-terminus points into the cytoplasm and C-terminus resides extracellularly. Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Similarly, KRRK basic residues of IFITM2/3 also contributed to suppressing ZIKV replication. Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Overall, our study provided topology, antiviral functional residues and the mechanism of interferon-inducible transmembrane proteins.

scholarly journals The Identification and Functional Characterization of WxL Proteins from Enterococcus faecium Reveal Surface Proteins Involved in Extracellular Matrix Interactions

2014 ◽  
Vol 197 (5) ◽  
pp. 882-892 ◽  
Author(s):  
Jessica R. Galloway-Peña ◽  
Xiaowen Liang ◽  
Kavindra V. Singh ◽  
Puja Yadav ◽  
Chungyu Chang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Bile Salt ◽  
Enterococcus Faecium ◽  
Bacterial Species ◽  
Functional Characterization ◽  
Surface Proteins ◽  
Type I ◽  
Gram Positive ◽  
Content Type

The WxL domain recently has been identified as a novel cell wall binding domain found in numerous predicted proteins within multiple Gram-positive bacterial species. However, little is known about the function of proteins containing this novel domain. Here, we identify and characterize 6Enterococcus faeciumproteins containing the WxL domain which, by reverse transcription-PCR (RT-PCR) and genomic analyses, are located in three similarly organized operons, deemed WxL loci A, B, and C. Western blotting, electron microscopy, and enzyme-linked immunosorbent assays (ELISAs) determined that genes of WxL loci A and C encode antigenic, cell surface proteins exposed at higher levels in clinical isolates than in commensal isolates. Secondary structural analyses of locus A recombinant WxL domain-containing proteins found they are rich in β-sheet structure and disordered segments. Using Biacore analyses, we discovered that recombinant WxL proteins from locus A bind human extracellular matrix proteins, specifically type I collagen and fibronectin. Proteins encoded by locus A also were found to bind to each other, suggesting a novel cell surface complex. Furthermore, bile salt survival assays and animal models using a mutant from which all three WxL loci were deleted revealed the involvement of WxL operons in bile salt stress and endocarditis pathogenesis. In summary, these studies extend our understanding of proteins containing the WxL domain and their potential impact on colonization and virulence inE. faeciumand possibly other Gram-positive bacterial species.

scholarly journals Cyclic Dimeric GMP Signaling Regulates Intracellular Aggregation, Sessility, and Growth of Ehrlichia chaffeensis

2011 ◽  
Vol 79 (10) ◽  
pp. 3905-3912 ◽  
Author(s):  
Yumi Kumagai ◽  
Junji Matsuo ◽  
Zhihui Cheng ◽  
Yoshihiro Hayakawa ◽  
Yasuko Rikihisa
Keyword(s):  
Serine Protease ◽  
Serine Proteases ◽  
Matrix Protein ◽  
Response Regulator ◽  
Bacterial Biofilm ◽  
Surface Proteins ◽  
Host Cells ◽  
Ehrlichia Chaffeensis ◽  
Content Type ◽  
Bacterial Surface

ABSTRACTCyclic dimeric GMP (c-di-GMP), a bacterial second messenger, is known to regulate bacterial biofilm and sessility. Replication of an obligatory intracellular pathogen,Ehrlichia chaffeensis, is characterized by formation of bacterial aggregates called morulae inside membrane-bound inclusions. WhenE. chaffeensismatures into an infectious form, morulae become loose to allow bacteria to exit from host cells to infect adjacent cells.E. chaffeensisexpresses a sensor kinase, PleC, and a cognate response regulator, PleD, which can produce c-di-GMP. A hydrophobic c-di-GMP antagonist, 2′-O-di(tert-butyldimethysilyl)-c-di-GMP (CDGA) inhibitsE. chaffeensisinternalization into host cells by facilitating degradation of some bacterial surface proteins via endogenous serine proteases. In the present study, we found that PleC and PleD were upregulated synchronously during exponential growth of bacteria, concomitant with increased morula size. While CDGA did not affect host cells, when infected cells were treated with CDGA, bacterial proliferation was inhibited, morulae became less compact, and the intracellular movement of bacteria was enhanced. Concurrently, CDGA treatment facilitated the extracellular release of bacteria with lower infectivity than those spontaneously released from sham-treated cells. Addition of CDGA to isolated inclusions induced dispersion of the morulae, degradation of an inclusion matrix protein TRP120, and bacterial intrainclusion movement, all of which were blocked by a serine protease inhibitor. These results suggest that c-di-GMP signaling regulates aggregation and sessility ofE. chaffeensiswithin the inclusion through stabilization of matrix proteins by preventing the serine protease activity, which is associated with bacterial intracellular proliferation and maturation.

scholarly journals Entamoeba histolytica Cell Surface Calreticulin Binds Human C1q and Functions in Amebic Phagocytosis of Host Cells

2012 ◽  
Vol 80 (6) ◽  
pp. 2008-2018 ◽  
Author(s):  
Archana Vaithilingam ◽  
Jose E. Teixeira ◽  
Peter J. Miller ◽  
Bradley T. Heron ◽  
Christopher D. Huston
Keyword(s):  
Cell Surface ◽  
Entamoeba Histolytica ◽  
Calcium Ionophore ◽  
Surface Expression ◽  
Surface Proteins ◽  
Host Cells ◽  
Content Type ◽  
Amebic Dysentery ◽  
Host Cell Apoptosis ◽  
Phagocytic Cups

ABSTRACTPhagocytosis of host cells is characteristic of tissue invasion by the intestinal amebaEntamoeba histolytica, which causes amebic dysentery and liver abscesses.Entamoeba histolyticainduces host cell apoptosis and uses ligands, including C1q, on apoptotic cells to engulf them. Two mass spectrometry analyses identified calreticulin in amebic phagosome preparations, and, in addition to its function as an endoplasmic reticulum chaperone, calreticulin is believed to be the macrophage receptor for C1q. The purpose of this study was to determine if calreticulin functions as anE. histolyticaC1q receptor during phagocytosis of host cells. Calreticulin was localized to the surface ofE. histolyticaduring interaction with both Jurkat lymphocytes and erythrocytes and was present in over 75% of phagocytic cups during amebic erythrophagocytosis. Presence of calreticulin on the cell surface was further demonstrated using a method that selectively biotinylated cell surface proteins and by flow cytometry using trophozoites overexpressing epitope-tagged calreticulin. Regulated overexpression of calreticulin increasedE. histolytica's ability to phagocytose apoptotic lymphocytes and calcium ionophore-treated erythrocytes but had no effect on amebic adherence to or destruction of cell monolayers or surface expression of the GalNAc lectin and serine-richE. histolyticaprotein (SREHP) receptors. Finally,E. histolyticacalreticulin bound specifically to apoptotic lymphocytes and to human C1q. Collectively, these data implicate cell surface calreticulin as a receptor for C1q duringE. histolyticaphagocytosis of host cells.

scholarly journals Analysis of Functional Domains of theEnterococcus faecalis Pheromone-Induced Surface Protein Aggregation Substance

2001 ◽  
Vol 183 (19) ◽  
pp. 5659-5667 ◽  
Author(s):  
C. M. Waters ◽  
G. M. Dunny
Keyword(s):  
Cell Surface ◽  
High Efficiency ◽  
Cell Surface Hydrophobicity ◽  
Surface Protein ◽  
Cell Aggregation ◽  
Surface Hydrophobicity ◽  
Host Cells ◽  
Functional Domains ◽  
Aggregation Substance ◽  
C Terminus

ABSTRACT Pheromone-inducible aggregation substance (AS) proteins ofEnterococcus faecalis are essential for high-efficiency conjugation of the sex pheromone plasmids and also serve as virulence factors during host infection. A number of different functions have been attributed to AS in addition to bacterial cell aggregation, including adhesion to host cells, adhesion to fibrin, increased cell surface hydrophobicity, resistance to killing by polymorphonuclear leukocytes and macrophages, and increased vegetation size in an experimental endocarditis model. Relatively little information is available regarding the structure-activity relationship of AS. To identify functional domains, a library of 23 nonpolar 31-amino-acid insertions was constructed in Asc10, the AS encoded by the plasmid pCF10, using the transposons TnlacZ/in and TnphoA/in. Analysis of these insertions revealed a domain necessary for donor-recipient aggregation that extends further into the amino terminus of the protein than previously reported. In addition, insertions in the C terminus of the protein also reduced aggregation. As expected, the ability to aggregate correlates with efficient plasmid transfer. The results also indicated that an increase in cell surface hydrophobicity resulting from AS expression is not sufficient to mediate bacterial aggregation.

scholarly journals Extracellular DNA, cell surface proteins and c-di-GMP promote biofilm formation in Clostridioides difficile

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lisa F. Dawson ◽  
Johann Peltier ◽  
Catherine L. Hall ◽  
Mark A. Harrison ◽  
Maria Derakhshan ◽  
...  
Keyword(s):  
Cell Surface ◽  
Biofilm Formation ◽  
Bacterial Species ◽  
Surface Proteins ◽  
Extracellular Dna ◽  
Cell Surface Proteins ◽  
Secondary Messenger ◽  
Clostridioides Difficile ◽  
Antibiotic Efficacy ◽  
Biofilm Matrix

AbstractClostridioides difficile is the leading cause of nosocomial antibiotic-associated diarrhoea worldwide, yet there is little insight into intestinal tract colonisation and relapse. In many bacterial species, the secondary messenger cyclic-di-GMP mediates switching between planktonic phase, sessile growth and biofilm formation. We demonstrate that c-di-GMP promotes early biofilm formation in C. difficile and that four cell surface proteins contribute to biofilm formation, including two c-di-GMP regulated; CD2831 and CD3246, and two c-di-GMP-independent; CD3392 and CD0183. We demonstrate that C. difficile biofilms are composed of extracellular DNA (eDNA), cell surface and intracellular proteins, which form a protective matrix around C. difficile vegetative cells and spores, as shown by a protective effect against the antibiotic vancomycin. We demonstrate a positive correlation between biofilm biomass, sporulation frequency and eDNA abundance in all five C. difficile lineages. Strains 630 (RT012), CD305 (RT023) and M120 (RT078) contain significantly more eDNA in their biofilm matrix than strains R20291 (RT027) and M68 (RT017). DNase has a profound effect on biofilm integrity, resulting in complete disassembly of the biofilm matrix, inhibition of biofilm formation and reduced spore germination. The addition of exogenous DNase could be exploited in treatment of C. difficile infection and relapse, to improve antibiotic efficacy.

scholarly journals Retraction ATPase motors are promiscuous among type IVa pilus systems

2021 ◽  
Author(s):  
Evan Couser ◽  
Jennifer L Chlebek ◽  
Ankur B Dalia
Keyword(s):  
Cell Surface ◽  
Vibrio Cholerae ◽  
Sequence Divergence ◽  
Similar Degree ◽  
Dna Uptake ◽  
Twitching Motility ◽  
Bacterial Surface ◽  
C Terminus ◽  
High Degree ◽  
Surface Dynamic

Bacterial surface appendages called type IVa pili (T4aP) promote diverse activities including DNA uptake, twitching motility, and virulence. These activities rely on the ability of T4aP to dynamically extend and retract from the cell surface. Dynamic extension relies on a motor ATPase commonly called PilB. Most T4aP also rely on specific motor ATPases, commonly called PilT and PilU, to dynamically and forcefully retract. Here, we systematically assess whether motor ATPases from 4 distinct T4aP could functionally complement Vibrio cholerae mutants that lacked their endogenous motors. We found that the retraction ATPases PilT and PilU are highly promiscuous and promote retraction of the V. cholerae competence T4aP despite a high degree of sequence divergence. In contrast, orthologous extension ATPases were not able to mediate extension of the V. cholerae competence T4aP despite a similar degree of sequence divergence. Also, we show that one of the PilT orthologs characterized does not support PilU-dependent retraction and we attributed this loss of activity to the 3' end of the gene, which suggests that the C-terminus of PilT plays an important role in promoting PilU-dependent retraction. Together, our data suggest that retraction ATPases have maintained a high degree of promiscuity for promoting retraction of diverse T4aP, while extension ATPases have evolved to become highly specific for their cognate systems.

Sign in / Sign up

Export Citation Format

Share Document