Schematic representation of the reaction catalyzed by microbial urease and the involvement of these enzymes in microbial physiology, human health, and disease.

<p>Schematic representation of the reaction catalyzed by microbial urease and the involvement of these enzymes in microbial physiology, human health, and disease.</p

Defense systems of the multi-species probiotic product VSL#3.

<p>Number of predicted restriction/modification enzymes (blue) and CRISPR-Cas spacers (green). Strains devoid of CRISPR-Cas loci have a number of spacers equal to zero.</p

General predicted genomic features of bacterial strains from VSL#3 product.

<p>General predicted genomic features of bacterial strains from VSL#3 product.</p

Pilus gene clusters identified in the multispecies product VSL#3.

<p>Both Tad pilus and sortase-dependent pilus gene clusters are shown along with a corresponding pilus gene cluster previously characterized [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192452#pone.0192452.ref017" target="_blank">17</a>]. The percentage indicates the degree of amino acid sequence conservation between the different genes.</p

Evaluation of minimal inhibitory concentration (MIC) of antibiotics against VSL#3 strains.

<p>The values in bold represent those MICs showing higher values compared to EFSA cut-off (in parenthesis) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192452#pone.0192452.ref040" target="_blank">40</a>]. n.d. not determined as not required by EFSA since these species show a high level of natural resistance [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192452#pone.0192452.ref040" target="_blank">40</a>].</p

CRISPR-Cas loci identified in the strains of the VSL#3 product.

<p>The CRISPR-Cas loci were identified using CRISPRFinder [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192452#pone.0192452.ref056" target="_blank">56</a>] and their gene order and predicted annotations are depicted along with their juxtaposing array of spacers. Legend: *, split gene.</p

Phylogenetic position of the strains from the VSL#3 product.

<p>This phylogenetic tree was generated based on the genome-predicted core proteome shared between the strains from the VSL#3 product and that of a set of relevant reference and representative strains. The position of the eight strains used for the formulation of the VSL#3 product are shaded in blue.</p

Promysalin is a salicylate-containing antimicrobial with a cell-membrane-disrupting mechanism of action on Gram-positive bacteria.

Promysalin was previously described as a narrow spectrum molecule with a unique species-specific activity against Pseudomonas aeruginosa. Here we demonstrate that promysalin is active against Gram-positive and Gram-negative bacteria using a microdilution assay. Promysalin acts on Gram-positive bacteria with a mechanism of action involving cell membrane damage with leakage of intracellular components. The evaluation of MICs and MBCs on 11 promysalin analogs, synthesized utilizing diverted total synthesis, allowed the identification of the structural moieties potentially involved in cell membrane interaction and damage. The mechanism of action of promysalin against Gram-negative bacteria is still not clarified, even if a synergistic effect with the bisguanidine chlorhexidine on cell membrane disruption has been observed