Circuitry rewiring directly couples competence to predation in the gut dweller Streptococcus salivarius

Small distortions in transcriptional networks might lead to drastic phenotypical changes, especially in cellular developmental programs such as competence for natural transformation. Here, we report a pervasive circuitry rewiring for competence and predation interplay in commensal streptococci. Canonically, in streptococci paradigms such as Streptococcus pneumoniae and Streptococcus mutans, the pheromone-based two-component system BlpRH is a central node that orchestrates the production of antimicrobial compounds (bacteriocins) and incorporates signal from the competence activation cascade. However, the human commensal Streptococcus salivarius does not contain a functional BlpRH pair, while the competence signaling system ComRS directly couples bacteriocin production and competence commitment. This network shortcut might underlie an optimal adaptation against microbial competitors and explain the high prevalence of S. salivarius in the human digestive tract. Moreover, the broad spectrum of bacteriocin activity against pathogenic bacteria showcases the commensal and genetically tractable S. salivarius species as a user-friendly model for competence and bacterial predation

Subtle selectivity in a pheromone sensor triumvirate desynchronizes competence and predation in a human gut commensal

Constantly surrounded by kin or alien organisms in nature, eukaryotes and prokaryotes developed various communication systems to coordinate adaptive multi-entity behavior. In complex and overcrowded environments, they require to discriminate relevant signals in a myriad of pheromones to execute appropriate responses. In the human gut commensal Streptococcus salivarius, the cytoplasmic Rgg/RNPP regulator ComR couples competence to bacteriocin-mediated predation. Here, we describe a paralogous sensor duo, ScuR and SarF, which circumvents ComR in order to disconnect these two physiological processes. We highlighted the recurring role of Rgg/RNPP in the production of antimicrobials and designed a robust genetic screen to unveil potent/optimized peptide pheromones. Further mutational and biochemical analyses dissected the modifiable selectivity toward their pheromone and operating sequences at the subtle molecular level. Additionally, our results highlight how we might mobilize antimicrobial molecules while silencing competence in endogenous populations of human microflora and temper gut disorders provoked by bacterial pathogens

The histidine kinase PdhS controls cell cycle progression of the pathogenic alphaproteobacterium Brucella abortus

Bacterial differentiation is often associated with the asymmetric localization of regulatory proteins, such as histidine kinases. PdhS is an essential and polarly localized histidine kinase in the pathogenic alphaproteobacterium Brucella abortus. After cell division, PdhS is asymmetrically segregated between the two sibling cells, highlighting a differentiation event. However, the function(s) of PdhS in the B. abortus cell cycle remains unknown. We used an original approach, the pentapeptide scanning mutagenesis method, to generate a thermosensitive allele of pdhS. We report that a B. abortus strain carrying this pdhS allele displays growth arrest and an altered DivK-yellow fluorescent protein (YFP) polar localization at the restrictive temperature. Moreover, the production of a nonphosphorylatable PdhS protein or truncated PdhS proteins leads to dominant-negative effects by generating morphological defects consistent with the inhibition of cell division. In addition, we have used a domain mapping approach combined with yeast two-hybrid and fluorescence microscopy methods to better characterize the unusual PdhS sensory domain. We have identified a fragment of the PdhS sensory domain required for protein-protein interaction (amino acids [aa] 210 to 434), a fragment sufficient for polar localization (aa 1 to 434), and a fragment (aa 527 to 661) whose production in B. abortus correlates with the generation of cell shape alterations. The data support a model in which PdhS acts as an essential regulator of cell cycle progression in B. abortus and contribute to a better understanding of the differentiation program inherited by the two sibling cells

Characterisation of the fumarase FumC and of its interaction with the essential histidine kinase PdhS at the old pole of Brucella abortus

Recently the bacterial pathogen Brucella abortus has been shown to asymmetrically divide in a reminiscent way compared to the leguminous symbiont Sinorhizobium meliloti and to the differentiation paradigm Caulobacter crescentus, two bacteria phylogenetically related to B. abortus. In C. crescentus, several proteins belonging to the well-known two-components signal transduction systems take a large part in the establishment of cellular asymmetry and in the differentiation process undergone by the flagellated cell type to become a stalked cell type. Strikingly many of these proteins have a homolog in B. abortus and S. meliloti, as predicted from genomes analysis, which suggests the possibility that a conserved network could operate an equivalent differentiation event in these two bacteria. Furthermore these two host-associated bacteria encode in their genome at least one supplementary protein protagonist. Therefore we focused our work on a main divergence in B. abortus and C. crescentus signalling network components namely the histidine kinase PdhS. We first demonstrated that pdhS gene is essential and that its protein product is asymmetrically distributed to focus at the old pole of B. abortus. This molecular behaviour strengthens the differentiation hypothesis in B. abortus. We subsequently identified the class II fumarate hydratase FumC (one of the key enzymes in the tricarboxylic acids cycle) as a partner of PdhS that specifically interacts with the "sensory" domain of PdhS. Logically FumC colocalizes with PdhS at the old pole of B. abortus while the B. abortus class I fumarate hydratase FumA that does not interact with PdhS remains scattered throughout the cytoplasm. Surprisingly we also discovered that the positional information encompassed in FumC is altered in its homologs in C. crescentus and S. meliloti. To sum up, our data suggest that the aforementioned bacteria that belong to the same taxonomic class share the common characteristic to differentiate albeit they have developed diverse mechanistic specificities along the evolution.(DOCSC03)--FUNDP, 200

A sweet twist gets Bacillus into shape

A protective organelle that is essential for viability under most conditions, the cell wall is a dynamic structure that is continuously remodelled with the growth of the bacterial cell. Because the cell wall also moulds the bacterium, the mechanisms of cell wall homeostasis can be deciphered using cell shape as a convenient proxy. In this issue of Molecular Microbiology, Foulquier et al. illuminate a connection between cell shape regulation and metabolism in Bacillus subtilis. They find that the putative NAD(P)-binding enzyme YvcK organizes into helical subcellular structures that exert shape control by directing the cell wall biosynthetic enzyme PBP1 along the cell cylinder and to the septum, a function shared with the MreB actin cytoskeleton. Unlike MreB, however, the role of YvcK in cell shape control is manifested only on certain carbon sources, presumably by way of a previously unknown metabolic feed that taps into cell morphogenesis

More than a Tad: spatiotemporal control of Caulobacter pili

The Type IV pilus (T4P) is a powerful and sophisticated bacterial nanomachine involved in numerous cellular processes, including adhesion, DNA uptake and motility. Aside from the well-described subtype T4aP of the Gram-negative genera, including Myxococcus, Pseudomonas and Neisseria, the Tad (tight adherence) pilus secretion system re-shuffles homologous parts from other secretion systems along with uncharacterized components into a new type of protein translocation apparatus. A representative of the Tad apparatus, the Caulobacter crescentus pilus assembly (Cpa) machine is built exclusively at the newborn cell pole once per cell cycle. Recent comprehensive genetic analyses unearthed a myriad of spatiotemporal determinants acting on the Tad/Cpa system, many of which are conserved in other α-proteobacteria, including obligate intracellular pathogens and symbionts

Peptides for inducing bacteriocin synthesis and methods to identify and/or select and/or optimize the same

Described herein is a peptide or peptidomimetic with a length of at least 6 residues comprising, consisting essentially of, or consisting of the sequence motif Xaa1-Trp-Xaa2-Xaa3-Xaa4-Xaa5 (SEQ ID NO:1), wherein: Xaa1 represents an aromatic residue (Phe, Tyr, Trp, His), Cys or Ser; Xaa2, Xaa3 and Xaa4 represent any residue; and Xaa5 represents Gly, lie or Val