Human salivary cystatin SA exhibits antimicrobial effect against <i>Aggregatibacter actinomycetemcomitans</i>

Ganeshnarayan, K.; Velliyagounder, Kabilan; Furgang, David; Dh, Fine

doi:10.1111/j.1600-0765.2012.01481.x

Cited by 27 publications

(23 citation statements)

References 51 publications

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“…Cystatin was detected in adult and in vitro- hatched L3 ESP. Cystatins from chickens and humans possess antibacterial activity (Blankenvoorde et al, 1998 ; Wesierska et al, 2005 ; Ganeshnarayan et al, 2012 ) whereas helminth cystatins, including from Ascaris , have a well-established role in modulating host immunity (Hartmann and Lucius, 2003 ; Mei et al, 2014 ; Coronado et al, 2017 ). Whether nematodes use cystatins to modulate the gut microbiota in addition to host immune cells requires further study.…”

Section: Resultsmentioning

confidence: 99%

The Intestinal Roundworm Ascaris suum Releases Antimicrobial Factors Which Interfere With Bacterial Growth and Biofilm Formation

Midha

Janek

Niewienda

et al. 2018

Front. Cell. Infect. Microbiol.

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Ascariasis is a widespread soil-transmitted helminth infection caused by the intestinal roundworm Ascaris lumbricoides in humans, and the closely related Ascaris suum in pigs. Progress has been made in understanding interactions between helminths and host immune cells, but less is known concerning the interactions of parasitic nematodes and the host microbiota. As the host microbiota represents the direct environment for intestinal helminths and thus a considerable challenge, we studied nematode products, including excretory-secretory products (ESP) and body fluid (BF), of A. suum to determine their antimicrobial activities. Antimicrobial activities against gram-positive and gram-negative bacterial strains were assessed by the radial diffusion assay, while effects on biofilm formation were assessed using the crystal violet static biofilm and macrocolony assays. In addition, bacterial neutralizing activity was studied by an agglutination assay. ESP from different A. suum life stages (in vitro-hatched L3, lung-stage L3, L4, and adult) as well as BF from adult males were analyzed by mass spectrometry. Several proteins and peptides with known and predicted roles in nematode immune defense were detected in ESP and BF samples, including members of A. suum antibacterial factors (ASABF) and cecropin antimicrobial peptide families, glycosyl hydrolase enzymes such as lysozyme, as well as c-type lectin domain-containing proteins. Native, unconcentrated nematode products from intestine-dwelling L4-stage larvae and adults displayed broad-spectrum antibacterial activity. Additionally, adult A. suum ESP interfered with biofilm formation by Escherichia coli, and caused bacterial agglutination. These results indicate that A. suum uses a variety of factors with broad-spectrum antibacterial activity to affirm itself within its microbe-rich environment in the gut.

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Section: Resultsmentioning

confidence: 99%

The Intestinal Roundworm Ascaris suum Releases Antimicrobial Factors Which Interfere With Bacterial Growth and Biofilm Formation

Midha

Janek

Niewienda

et al. 2018

Front. Cell. Infect. Microbiol.

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“…Recently we have isolated a salivary substance that kills Aa in vitro from a periodontally healthy adolescent devoid of Aa . 31 This substance, cystatin SA, is found in high concentrations in saliva from healthy subjects and in sublethal concentrations in subjects who have LAP. 31,32 Of the three salivary activity parameters examined in this study, Lf iron levels, IgA agglutination, and salivary killing of Gram-positive bacteria, the Lf iron levels per unit of total Lf appear to show the clearest distinction between Aa -carriers who remain healthy and those who develop disease.…”

Section: Discussionmentioning

confidence: 99%

Can salivary activity predict periodontal breakdown in A. actinomycetemcomitans infected adolescents?

Fine

Furgang

McKiernan

et al. 2013

Archives of Oral Biology

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Objective While Aggregatibacter actinomycetemcomitans (Aa) is highly associated with localized aggressive periodontitis (LAP) many Aa-carriers do not develop LAP. This study was designed to determine whether specific salivary factors could distinguish between subjects who have Aa initially and remain healthy (H/AA) as compared to those who develop LAP (LAP/AA). Design H/AA subjects and healthy controls with no Aa (H) were enrolled in a longitudinal cohort study to investigate initiation of bone loss (LAP) over 3 years. After detection of LAP, stored saliva from 10 H, 10 H/AA, and 10 LAP/AA subjects was thawed, processed, and tested for; 1) lactoferrin (Lf) concentration and iron levels, 2) agglutination of Aa; 3) killing of Gram-positive bacteria. Results LAP/AA saliva levels of Lf iron were low prior to and after bone loss (3.6 ± 1.7 ng Fe/µg (LAP/AA vs. H and H/AA p ≤ 0.01). Saliva from H/AA subjects caused Aa to agglutinate significantly more than H or LAP/AA saliva (p ≤ 0.01). LAP/AA saliva killed Streptococcus mutans, S. sanguis and Lactobacillus in vitro by > 83%. Saliva from H individuals killed these bacteria by < 3.3% (LAP/AA vs. H; p ≤ 0.01). H/AA killing was intermediate. Conclusions LAP/AA saliva showed: low levels of Lf iron, minimal Aa agglutinating activity, and high killing activity against Gram-positive bacteria. Aa-positive healthy saliva (H/AA) showed: higher levels of Lf iron, maximal Aa agglutinating activity, and moderate killing of Gram-positive bacteria. A salivary activity profile can distinguish between subjects who are Aa-positive and remain healthy from those who develop LAP.

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“…This is the first study to describe CST2 expression in BAL. CST2 is an extracellular antimicrobial peptide with protease inhibitory activity previously described as originating from saliva [27]. There is limited information regarding the role of cystatins in immune responses.…”

Section: Discussionmentioning

confidence: 99%

Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans

et al. 2018

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Diesel exhaust (DE) is a paradigm for traffic-related air pollution. Human adaptation to DE is poorly understood and currently based on oversimplified models. DE promotes allergic responses, but protein expression changes mediated by this interaction have not been systematically investigated. The aim of this study was to define the effect of inhaled DE on allergen-induced proteins in the lung.We performed a randomised and blinded controlled human crossover exposure study. Participants inhaled filtered air or DE; thereafter, contralateral lung segments were challenged with allergen or saline. Using label-free quantitative proteomics, we comprehensively defined DE-mediated alteration of allergen-driven secreted proteins (secretome) in bronchoalveolar lavage. We further examined expression of proteins selected from the secretome data in independent validation experiments using Western blots, ELISA and immunohistochemistry.We identified protein changes unique to co-exposure (DE+allergen), undetected with mono-exposures (DE or allergen alone). Validation studies confirmed that specific proteins ( the antimicrobial peptide cystatin-SA) were significantly enhanced with DE+allergen compared to either mono-exposure.This study demonstrates that common environmental co-exposures can uniquely alter protein responses in the lungs, illuminating biology that mono-exposures cannot. This study highlights the value of complex human models in detailing airway responses to inhaled pollution.

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Human salivary cystatin SA exhibits antimicrobial effect against Aggregatibacter actinomycetemcomitans

Cited by 27 publications

References 51 publications

The Intestinal Roundworm Ascaris suum Releases Antimicrobial Factors Which Interfere With Bacterial Growth and Biofilm Formation

The Intestinal Roundworm Ascaris suum Releases Antimicrobial Factors Which Interfere With Bacterial Growth and Biofilm Formation

Can salivary activity predict periodontal breakdown in A. actinomycetemcomitans infected adolescents?

Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans

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