A toxin-antitoxin module of Salmonella promotes virulence in mice
Authors: Stéphane Méresse
Weidong Zhao
Miguel A De la Cruz
Carine Farenc
Christian Cambillau
Didier Raoult
Grégory Gimenez
Jean-Pierre Gorvel
Journal: PLoS Pathogens (2013)
Discipline: MICROBIOLOGY
Keywords: Toxin-antitoxin modules; bacteria; archaea; plasmids; bacterial chromosomes
Affiliations: Aix-Marseille University, CIML, Marseille, France ; CNRS, UMR 7280, Marseille, France ; INSERM, U631, Marseille, France., Aix-Marseille University, AFMB, Marseille, France ; CNRS, UMR 7257, Marseille, France., URMITE, CNRS-IRD UMR 6236, Marseille, France.

Abstract:  Toxin-antitoxin (TA) modules are widely prevalent in both bacteria and archaea. Originally described as stabilizing elements of plasmids, TA modules are also widespread on bacterial chromosomes. These modules promote bacterial persistence in response to specific environmental stresses. So far, the possibility that TA modules could be involved in bacterial virulence has been largely neglected, but recent comparative genomic studies have shown that the presence of TA modules is significantly associated with the pathogenicity of bacteria. Using Salmonella as a model, we investigated whether TA modules help bacteria to overcome the stress conditions encountered during colonization, thereby supporting virulence in the host. By bioinformatics analyses, we found that the genome of the pathogenic bacterium Salmonella Typhimurium encodes at least 11 type II TA modules. Several of these are conserved in other pathogenic strains but absent from non-pathogenic species indicating that certain TA modules might play a role in Salmonella pathogenicity. We show that one TA module, hereafter referred to as sehAB, plays a transient role in virulence in perorally inoculated mice. The use of a transcriptional reporter demonstrated that bacteria in which sehAB is strongly activated are predominantly localized in the mesenteric lymph nodes. In addition, sehAB was shown to be important for the survival of Salmonella in these peripheral lymphoid organs. These data indicate that the transient activation of a type II TA module can bring a selective advantage favouring virulence and demonstrate that TA modules are engaged in Salmonella pathogenesis. 

Retracted: Yes

PubPeer comments:
 Figure S4. Could the authors please check? * Red boxes: Three lanes appear to look similar to each other. * Green arrows: Sharp vertical background transitions appear to be visible between lanes Image made darker to bring out details. ![file] , 
 This image should never have been published and we apologize for this mistake. Below two similar experiences leading to the same conclusion.![file] , 
 Thank you Dr. Mu00e9resse. Just out of curiosity, how can three seemingly identical lanes end up in the same blot by mistake? , 
 #1 I see the three bands reasonnably different ![file] , 
 #4 It appears that the last author agrees that the original image is faulty, although they are so far silent on how it could have occurred by accident (which seems impossible) or whether they intend to contact the journal to correct the scientific record. , 
 Answer to #4, from a computer scientist working on image analysis for more than ten years. If we assume that the three bands are identical, then these slight differences could be easily be due to compression artifacts if in any step in the image processing pipeline and PDF compilation a lossy image compression is used. Of course, if we assume they are different, there is no need to think further about this - and due to my curriculum I am in no way competent to judge this. If we equalize the image, we can see that not only the dark areas have extremely similar shapes, but the background noise also shares similar patterns, while this does not happen in any other part of the figure. Thus, we can assert that whole lanes are highly similar. ![file] I would, also out of pure curiosity, be interested in knowing how noise patterns in the background can share such similarity. , 
 #3 The most obvious explanation is that the person who conducted the experience wanted to offer a quality image for the publication and merged two or more blots into a single one. Not best practice. , 
 #6 how noise patterns in the background can share such similarity Maybe just because the same sensor lens association is used each time. Digital imaging sensors sport distinctive, consistent, patterns, you can evaluate with a white shot. https: www.researchgate.net publication 3455253_Digital_Camera_Identification_From_Sensor_Pattern_Noise , 
 #8 As you point out, sensor fixed-pattern noise generally only shows up at saturation, which was unlikely to be the case during image acquisition. , 
 October 21, 2020 retraction. https: journals.plos.org plospathogens article?id=10.1371 journal.ppat.1009031 It reads:  Following the publication of this article [1], concerns were raised regarding the data presented in Fig 3D and S4 Fig. Specifically, In Fig 3D, a straight vertical signal can be observed directly on the left of the band in lane 3, which appears to be inconsistent with the overall background of the blot. The corresponding author was unable to explain the presence of this signal. In S4 Fig, the bands and background signal of lanes 1, 2, and 7 appear similar. In addition, the background signal directly surrounding all bands presented in this panel appears to be inconsistent with the overall background of S4 Fig. The corresponding author has indicated that the image was not intended for publication. The underlying data for the results presented in Fig 3D and S4 Fig are no longer available. In light of the concerns affecting multiple figure panels that question the integrity of these data, the PLOS Pathogens Editors retract this article. JPG and SM did not agree with the retraction. MADlC agreed with the retraction. WZ, CF, GG, DR and CC either did not respond directly or could not be reached. ,