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Pathogens and Disease

Kouki Yoshikawa, Yuichiro Kikuchi, Eitoyo Kokubu, Kentaro Imamura, Atsushi Saito, Kazuyuki Ishihara
Interaction between two periodontal pathogens, Porphyromonas gingivalis and Treponema denticola, contributes to plaque biofilm formation. P. gingivalis forms aggregates with T. denticola through its adhesion/hemagglutinin domain (Hgp44). In this study, we investigated the specific domain of P. gingivalis Hgp44 responsible for adhesion to T. denticola using expression vectors harboring P. gingivalis Hgp44 DNA sequences encoding amino acid residues 1-419. Six plasmids harboring fragments in this region were generated by PCR amplification and self-ligation, and recombinant proteins r-Hgp44 (residues 1-419), r-Hgp441 (residues 1-124), r-Hgp442 (1-199), r-Hgp443 (1-316), r-Hgp444 (199-419), r-Hgp445 (124-198), and r-Hgp446 (199-316) were produced, as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting...
May 16, 2018: Pathogens and Disease
Mengfei Ho, Amel Mettouchi, Brenda A Wilson, Emmanuel Lemichez
Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic E. coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer...
May 3, 2018: Pathogens and Disease
Luis Franco, Juan Cedano, JosepAntoni Perez-Pons, Angel Mozo-Villarias, Jaume Piñol, Isaac Amela, Enrique Querol
Moonlighting or multitasking proteins refer to those proteins with two or more functions performed by a single polypeptide chain. Proteins that belong to key ancestral functions and metabolic pathways such as primary metabolism typically exhibit moonlighting phenomenon. We have collected 698 moonlighting proteins in MultitaskProtDB-II database. A survey shows that 25% of the proteins of the database correspond to moonlighting functions related to pathogens virulence activity. Why is the canonical function of these virulence proteins mainly from ancestral key biological functions (especially of primary metabolism)? Our hypothesis is that these proteins present a high conservation between the pathogen protein and the host counterparts...
April 30, 2018: Pathogens and Disease
Kwok-Ho Lam, Stefan Sikorra, Jasmin Weisemann, Hannah Maatsch, Kay Perry, Andreas Rummel, Thomas Binz, Rongsheng Jin
The extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a ∼2.09 Å resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites...
April 23, 2018: Pathogens and Disease
Yilin Wu, Isaac Klapper, Philip S Stewart
Infections associated with microbial biofilms are often found to involve hypoxic or anoxic conditions within the biofilm or its vicinity. To shed light on the phenomenon of local oxygen depletion, mathematical reaction-diffusion models were derived that integrated the two principal oxygen sinks, microbial respiration and neutrophil consumption. Three simple one-dimensional problems were analyzed approximating biofilm near an air interface as in a dermal wound or mucus layer, biofilm on an implanted medical device, or biofilm aggregates dispersed in mucus or tissue...
April 23, 2018: Pathogens and Disease
Michael J Mansfield, Andrew C Doxey
Clostridial neurotoxins, which include botulinum and tetanus neurotoxins, have evolved a remarkably sophisticated structure and molecular mechanism fine-tuned for the targeting and cleavage of vertebrate neuron substrates leading to muscular paralysis. How and why did this toxin evolve? From which ancestral proteins are BoNTs derived? And what is, or was, the primary ecological role of BoNTs in the environment? In this article, we examine these questions in light of recent studies identifying homologs of BoNTs in the genomes of non-clostridial bacteria, including Weissella, Enterococcus, and Chryseobacterium...
April 19, 2018: Pathogens and Disease
Dusan Milivojevic, Neven Šumonja, Strahinja Medic, Aleksandar Pavic, Ivana Moric, Branka Vasiljevic, Lidija Senerovic, Jasmina Nikodinovic-Runic
Pseudomonas aeruginosa, has been amongst top 10 'superbugs' worldwide and is causing infections with poor outcomes in both humans and animals. From 202 P. aeruginosa isolates (n = 121 animal and n = 81 human) 40 were selected on the basis of biofilm-forming ability and were comparatively characterized in terms of virulence determinants to the type strain P. aeruginosa PAO1. Biofilm formation, pyocyanin and hemolysins production and bacterial motility patterns were compared to the ability to kill human cell line A549 in vitro...
April 19, 2018: Pathogens and Disease
Ling Zhang, Qianqian Qin, Manni Liu, Xiangling Zhang, Fang He, Guoqing Wang
This study aimed to investigate how Akkermansia muciniphila can implicate type 2 diabetes mellitus and the mechanisms underlying the effects Akkermansia muciniphila on type 2 diabetes mellitus. Normal and streptozotocin-induced diabetic Sprague-Dawley rats were orally administered with Akkermansia muciniphila and solvent. After four weeks of treatment, diabetic rats orally administered with live or pasteurized Akkermansia muciniphila exhibited significant increase in the blood concentration of high-density lipoprotein, and decrease in the hepatic glycogen, serum plasminogen activator inhibitor-1, tumor necrosis factor-α, lipopolysaccharide, malondialdehyde, and total glucagon-like peptide-1...
April 16, 2018: Pathogens and Disease
Karkowska-Kuleta Justyna, Dominika Bartnicka, Marcin Zawrotniak, Gabriela Zielinska, Anna Kieronska, Oliwia Bochenska, Izabela Ciaston, Joanna Koziel, Jan Potempa, Zbigniew Baster, Zenon Rajfur, Maria Rapala-Kozik
Porphyromonas gingivalis, an anaerobic Gram-negative bacterium critically involved in the development of human periodontitis, belongs to the late colonizers of the oral cavity. The success of this pathogen in the host colonization and infection results from the presence of several virulence factors, including extracellular peptidylarginine deiminase (PPAD), an enzyme that converts protein arginine residues to citrullines. A common opportunistic fungal pathogen of humans, Candida albicans, is also frequently identified among microorganisms that reside at subgingival sites...
April 12, 2018: Pathogens and Disease
Jack Guinan, Pedro Villa, Shankar Thangamani
Candida albicans is one of the most common causes of fungal infections in humans with a significant mortality rate. However, the factors involved in C. albicans gastrointestinal (GI) colonization remain unclear. We hypothesize that secondary bile acids have direct antifungal activity against C. albicans and may play a critical role in maintaining GI colonization resistance against C. albicans. In this study, we investigated the effect of secondary bile acids including lithocholic acid (LCA) and deoxycholic acid (DCA) on C...
April 10, 2018: Pathogens and Disease
Amie Maher, Kara Staunton, Kevin Kavanagh
A potential role for bacteria in the induction of rosacea has been suggested. The aim of this work was to characterize the effect of temperature on the production of immunostimulatory proteins by Bacillus oleronius-a bacterium to which rosacea patients show sera reactivity and which was originally isolated from a Demodex mite from a rosacea patient. The affected skin of rosacea patients is at a higher temperature than unaffected skin and it was postulated that this might alter the protein expression pattern of B...
April 10, 2018: Pathogens and Disease
Graciela Rodríguez-Sevilla, Charlotte Rigauts, Eva Vandeplassche, Lisa Ostyn, Ignacio Mahíllo-Fernández, Jaime Esteban, Concepción Pérez-Jorge Peremarch, Tom Coenye, Aurélie Crabbé
Mycobacterium abscessus lung infection is a major health problem for cystic fibrosis (CF) patients. Understanding the in vivo factors that influence the outcome of therapy may help addressing the poor correlation between in vitro and in vivo antibiotic efficacy. We evaluated the influence of interspecies interactions and lung epithelial cells on antibiotic efficacy. Therefore, single and dual species biofilms of M. abscessus and a major CF pathogen (Pseudomonas aeruginosa) were cultured on a plastic surface or on in vivo-like three-dimensional (3-D) lung epithelial cells, and the activity of antibiotics (colistin, amikacin, clarithromycin, ceftazidime) in inhibiting biofilm formation was evaluated...
April 10, 2018: Pathogens and Disease
Amel Ben Lagha, Sabine Groeger, Joerg Meyle, Daniel Grenier
The gingival epithelium, a stratified squamous tissue that acts as an interface between the external environment and the underlying connective tissue, plays an active role in maintaining periodontal health. The aim of the present study was to investigate the ability of green tea catechins to enhance gingival epithelial barrier function and protect against the disruption of epithelial integrity induced by Porphyromonas gingivalis. Both the green tea extract and epigallocatechin-3-gallate (EGCG) dose- and time-dependently increased the transepithelial electrical resistance (TER) of a gingival keratinocyte model and decreased the permeability of the cell monolayer to FITC-conjugated 4...
April 4, 2018: Pathogens and Disease
Jacob D Pierson, Melanie A Hansmann, Catherine C Davis, Larry J Forney
Menstrual toxic shock syndrome is associated with vaginal colonization by Staphylococcus aureus strains that encode toxic shock syndrome toxin 1 (tst+). Interestingly, a small proportion of women are colonized by S. aureus tst+ but do not have symptoms of toxic shock syndrome. Here we sought to determine if differences in the species composition of vaginal bacterial communities reflect a differential risk of colonization by S. aureus capable of producing toxic shock syndrome toxin 1 (TSST-1). The composition of vaginal communities of women that were or were not colonized with S...
June 1, 2018: Pathogens and Disease
S Upadhyay, E Mittal, J A Philips
Macrophages are first-line responders against microbes. The success of Mycobacterium tuberculosis (Mtb) rests upon its ability to convert these antimicrobial cells into a permissive cellular niche. This is a remarkable accomplishment, as the antimicrobial arsenal of macrophages is extensive. Normally bacteria are delivered to an acidic, degradative lysosome through one of several trafficking pathways, including LC3-associated phagocytosis (LAP) and autophagy. Once phagocytozed, the bacilli are subjected to reactive oxygen and nitrogen species, and they induce the expression of proinflammatory cytokines, which serve to augment host responses...
June 1, 2018: Pathogens and Disease
Julia Puffal, Alam García-Heredia, Kathryn C Rahlwes, M Sloan Siegrist, Yasu S Morita
The mycobacterial cell envelope is a complex multilayered structure that provides the strength to the rod-shaped cell and creates the permeability barrier against antibiotics and host immune attack. In this review, we will discuss the spatial coordination of cell envelope biosynthesis and how plasma membrane compartmentalization plays a role in this process. The spatial organization of cell envelope biosynthetic enzymes as well as other membrane-associated proteins is crucial for cellular processes such as polar growth and midcell septum formation...
June 1, 2018: Pathogens and Disease
Shamba Gupta, G Marcela Rodriguez
Mycobacteria, like other bacteria, archaea and eukaryotic cells, naturally release extracellular vesicles (EVs) to interact with their environment. EVs produced by pathogenic bacteria are involved in many activities including cell-cell communication, immunomodulation, virulence and cell survival. Although EVs released by thick cell wall microorganisms like mycobacteria were recognized only recently, studies of Mycobacterium tuberculosis EVs already point to their important roles in host pathogen interactions, opening exciting new areas of investigation...
June 1, 2018: Pathogens and Disease
Joanne Turner, Jordi B Torrelles
Mannose-capped lipoarabinomannan (ManLAM), present in all members of the Mycobacterium tuberculosis complex and in other pathogenic Mycobacterium spp, is a high molecular mass amphipathic lipoglycan with a defined critical role in mycobacterial survival during infection. In particular, ManLAM is well-characterized for its importance in providing M. tuberculosis a safe portal of entry to phagocytes, regulating the intracellular trafficking network, as well as immune responses of infected host cells. These ManLAM immunological characteristics are thought to be linked to the subtle but unique and well-defined structural characteristics of this molecule, including but not limited to the degree of acylation, the length of the D-mannan and D-arabinan cores, the length of the mannose caps, as well as the presence of other acidic constituents such as succinates, lactates and/or malates, and also the presence of 5-methylthioxylosyl...
June 1, 2018: Pathogens and Disease
Arissa Felipe Borges, Rodrigo Saar Gomes, Fátima Ribeiro-Dias
Leishmania (Viannia) guyanensis is a causal agent of American tegumentary leishmaniasis (ATL). This protozoan has been poorly investigated; however, it can cause different clinical forms of ATL, ranging from a single cutaneous lesion to severe lesions that can lead to destruction of the nasopharyngeal mucosa. L. (V.) guyanensis and the disease caused by this species can present unique aspects revealing the need to better characterize this parasite species to improve our knowledge of the immunopathological mechanisms and treatment options for ATL...
June 1, 2018: Pathogens and Disease
Hannah B Pooley, Karren M Plain, Auriol C Purdie, Douglas J Begg, Richard J Whittington, Kumudika de Silva
Experimental trials in the natural host are essential for development and screening of effective vaccines. For chronic diseases of livestock such as paratuberculosis, these can be lengthy and costly in nature. An alternative is to screen vaccines in vitro; however, previous studies have found that vaccine success in vitro in existing screening assays does not translate to in vivo efficacy. To overcome these issues, we have developed a system that combines both in vivo and in vitro aspects. We hypothesise that the effectiveness of vaccine-induced immune responses mounted in vivo could be gauged by assessing the ability of immune cells to 'control' an in vitro infection...
April 1, 2018: Pathogens and Disease
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