Distinct interactions with cellular E-cadherin of the two virulent metalloproteinases encoded by a Bacteroides fragilis pathogenicity island
Authors: Alex Y Strongin
Sergey A Shiryaev
Albert G Remacle
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Bacteroides fragilis; pathogenicity island; enterotoxigenic B. fragilis; secretory metalloproteinase II; enterotoxigenic fragilysin isoenzymes
Affiliations: Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.

Abstract:  Bacteroides fragilis causes the majority of Gram-negative anaerobic infections in the humans. The presence of a short, 6-kb, pathogenicity island in the genome is linked to enterotoxigenic B. fragilis (ETBF). The role of the enterotoxin in B. fragilis virulence, however, remains to be determined, as the majority of clinical isolates lack ETBF genes and healthy individuals carry enterotoxin-positive B. fragilis. The island encodes secretory metalloproteinase II (MPII) and one of three homologous enterotoxigenic fragilysin isoenzymes (FRA; also termed B. fragilis toxin or BFT). The secretory metalloproteinases expressed from the genes on the B. fragilis pathogenicity island may have pathological importance within the gut, not linked to diarrhea. MPII and FRA are counter-transcribed in the bacterial genome, implying that regardless of their structural similarity and overlapping cleavage preferences these proteases perform distinct and highly specialized functions in the course of B. fragilis infection. The earlier data by us and others have demonstrated that FRA cleaves cellular E-cadherin, an important adherens junction protein, and weakens cell-to-cell contacts. Using E-cadherin-positive and E-cadherin-deficient cancer cells, and the immunostaining, direct cell binding and pull-down approaches, we, however, demonstrated that MPII via its catalytic domain efficiently binds, rather than cleaves, E-cadherin. According to our results, E-cadherin is an adherens junction cellular receptor, rather than a proteolytic target, of the B. fragilis secretory MPII enzyme. As a result of the combined FRA and MPII proteolysis, cell-to-cell contacts and adherens junctions are likely to weaken further. 

Retracted: No

PubPeer comments:
 Figure 5. * Red boxes. In the top row of the B panels, the FRA3 and FRA3-E349A panels appear to show an overlap. ![file] , 
 Expression of Concern, [6 June 2022] . --------------------- Following the publication of this article [1], concerns were raised regarding results presented in Figs 1 and 5. Specifically, - In Fig 1B, when colour levels are adjusted, two rectangular areas in the background appear lighter than the rest of the background. - In Fig 5B, brightfield images for FRA3 and FRA3-E349A appear to partially overlap. The corresponding author stated that they no longer have access to the raw data underlying the above figures or the other figures of this article. As the raw data are no longer available, the article is not in compliance with PLOS ONEu2019s Data Availability policy that was in place at the time of the articleu2019s submission. The corresponding author stated that the rectangular areas in the background of Fig 1B may have occurred in the course of figure preparation, and they provided an alternative version of Fig 1 (included with this notice). The rectangular areas are also visible in the background of the alternative version of Fig 1B when colour levels are adjusted. The editors remain concerned about this figure, and consider the issue unresolved in the absence of raw data. The corresponding author acknowledged that the bright-field images for FRA3 and FRA3-E349A partially overlap, and stated that this occurred due to an error in figure preparation. They were unable to provide replacements for the overlapping panels, and in the absence of raw data, it is not possible to confirm which panel accurately presents the described results. Therefore, an updated version of Fig 5 is provided here in which both overlapping panels have been redacted. The corresponding author stated that the findings presented in Fig 5B are supported by results presented in Figs 1B, 2C, 5A and 6A. The PLOS ONE Editors issue this Expression of Concern to notify readers of the above image concerns which are not fully resolved, and of the unavailability of raw data underlying the results in this article. ![] ![] , 
 Here is the original Figure 1B, made a bit darker to bring out the rectangles described in the Expression of Concern: ![file] ,