A Role for Salivary Peptides in the Innate Defense Against Enterotoxigenic Escherichia coli

Brown, Jeffrey W.; Badahdah, Arwa; Iticovici, Micah; Vickers, Tim J.; Alvarado, David M.; Helmerhorst, Eva J.; Oppenheim, Frank G.; Mills, Jason C.; Ciorba, Matthew A.; Fleckenstein, James M.; Bullitt, Esther

doi:10.1093/infdis/jiy032

Cited by 13 publications

(13 citation statements)

References 32 publications

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“…These important components of saliva are reviewed elsewhere [37–40]. The antimicrobial activity of salivary proteins may even extend beyond the oropharynx into the proximal digestive tract, there exerting specific antimicrobial activity against enteric pathogens [41]. Besides antimicrobial components, saliva also contains growth factors and cytokines that likely play a role in wound healing in the oral cavity, oropharynx, and esophagus [42, 43].…”

Section: Host-derived Innate and Immune-related Compounds In Human Samentioning

confidence: 99%

Glycan recognition at the saliva – oral microbiome interface

Cross

Rühl

2018

Cellular Immunology

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The mouth is a first critical interface where most potentially harmful substances or pathogens contact the host environment. Adaptive and innate immune defense mechanisms are established there to inactivate or eliminate pathogenic microbes that traverse the oral environment on the way to their target organs and tissues. Protein and glycoprotein components of saliva play a particularly important role in modulating the oral microbiota and helping with the clearance of pathogens. It has long been acknowledged that glycobiological and glycoimmunological aspects play a pivotal role in oral host-microbe, microbe-host, and microbe-microbe interactions in the mouth. In this review, we aim to delineate how glycan-mediated host defense mechanisms in the oral cavity support human health. We will describe the role of glycans attached to large molecular size salivary glycoproteins which act as a first line of primordial host defense in the human mouth. We will further discuss how glycan recognition contributes to both colonization and clearance of oral microbes.

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Section: Host-derived Innate and Immune-related Compounds In Human Samentioning

confidence: 99%

Glycan recognition at the saliva – oral microbiome interface

Cross

Rühl

2018

Cellular Immunology

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“…A) Negative stain data of CFA/I using transmission electron microscopy (left), segmentation results (middle), statistical dataset (right). The conversion factor is 0.423 nm/pixel (Brown et al 2018). B) A video frame from a F-pilus diffusion video recorded using fluorescence microscopy (left), segmentation result (middle), statistical dataset (right).…”

Section: Comparison Of Methodsmentioning

confidence: 99%

“…In addition to these experiments we show as a proof of concept that DSeg can segment various images/videos. For example, we extracted structural parameters of negative stain CFA/I adhesion pili Brown et al (2018), diffusion of a F-pilus Silverman and Clarke (2010), and digital in-line holographic microscopy data of S. coelicolor ( Fig S4).…”

Section: Demonstration and Evaluation Of Dsegmentioning

confidence: 99%

DSeg: A dynamic image segmentation program to extract backbone patterns for filamentous bacteria and hyphae structures

Zhang

Söderholm

Sandblad

et al. 2018

Preprint

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Motivation: Quantitative image analysis of growing filamentous fungi and prokaryotes are important to detect and evaluate morphological effects of growth conditions, compounds and mutations. However, analysis of time-series image data is often limited by the ability of the algorithms to accurately segment structures that are complicated or if an organism is within a crowded population. To overcome these issues we present DSeg; an image analysis program designed to process time-series image data as well as single images to find multiple filamentous structures e.g., filamentous prokaryotes, yeasts and molds using a dynamic segmentation approach. DSeg automatically segments and analyzes objects, includes drift correction, and outputs statistical data such as persistence length, growth rate and growth direction. Availability and implementation: DSeg is a free open-source program written in MATLAB. DSeg can be downloaded as a package from https://sourceforge.net/projects/dseg-software. Contact: magnus.andersson@umu.se and hanqing.zhang@umu.se Supplementary information: Supplementary data are available at online.

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“…Hydrophobicity maps (Kyte & Doolittle, 1982; arbitrary units, from À4.5 to 4.5) of surface-exposed residues for individual subunits are shown oriented so that the outer surface (a, top) or the surface that accepts the N-terminal extension from the adjacent subunit (b, bottom) is visible. The charge distribution (in kcal mol À1 at 25 C) on the outer surface (c) and the inner surface (d) of the pilus shows a negatively charged inner surface that could provide a target for positively charged disruptive therapeutic molecules/peptides such as histatins (Brown et al, 2018).…”

Section: Figurementioning

confidence: 99%

Cryo-EM structure of the CFA/I pilus rod

Zheng

Andersson

Mortezaei

et al. 2019

IUCrJ

Self Cite

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Enterotoxigenic Escherichia coli (ETEC) are common agents of diarrhea for travelers and a major cause of mortality in children in developing countries. To attach to intestinal cells ETEC express colonization factors, among them CFA/I, which are the most prevalent factors and are the archetypical representative of class 5 pili. The helical quaternary structure of CFA/I can be unwound under tensile force and it has been shown that this mechanical property helps bacteria to withstand shear forces from fluid motion. We report in this work the CFA/I pilus structure at 4.3 Å resolution from electron cryomicroscopy (cryo-EM) data, and report details of the donor strand complementation. The CfaB pilins modeled into the cryo-EM map allow us to identify the buried surface area between subunits, and these regions are correlated to quaternary structural stability in class 5 and chaperone–usher pili. In addition, from the model built using the EM structure we also predicted that residue 13 (proline) of the N-terminal β-strand could have a major impact on the filament's structural stability. Therefore, we used optical tweezers to measure and compare the stability of the quaternary structure of wild type CFA/I and a point-mutated CFA/I with a propensity for unwinding. We found that pili with this mutated CFA/I require a lower force to unwind, supporting our hypothesis that Pro13 is important for structural stability. The high-resolution CFA/I pilus structure presented in this work and the analysis of structural stability will be useful for the development of novel antimicrobial drugs that target adhesion pili needed for initial attachment and sustained adhesion of ETEC.

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A Role for Salivary Peptides in the Innate Defense Against Enterotoxigenic Escherichia coli

Cited by 13 publications

References 32 publications

Glycan recognition at the saliva – oral microbiome interface

Glycan recognition at the saliva – oral microbiome interface

DSeg: A dynamic image segmentation program to extract backbone patterns for filamentous bacteria and hyphae structures

Cryo-EM structure of the CFA/I pilus rod

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