Regulation of type VI secretion systems at the transcriptional, posttranscriptional and posttranslational level.

Bacteria live in complex polymicrobial communities and are constantly competing for resources. The type VI secretion system (T6SS) is a widespread antagonistic mechanism used by Gram-negative bacteria to gain an advantage over competitors. T6SSs translocate toxic effector proteins inside target prokaryotic cells in a contact-dependent manner. In addition, some T6SS effectors can be secreted extracellularly and contribute to the scavenging scarce metal ions. Bacteria deploy their T6SSs in different situations, categorizing these systems into offensive, defensive and exploitative. The great variety of bacterial species and environments occupied by such species reflect the complexity of regulatory signals and networks that control the expression and activation of the T6SSs. Such regulation is tightly controlled at the transcriptional, posttranscriptional and posttranslational level by abiotic (e.g. pH, iron) or biotic (e.g. quorum-sensing) cues. In this review, we provide an update on the current knowledge about the regulatory networks that modulate the expression and activity of T6SSs across several species, focusing on systems used for interbacterial competition.

Intercepting biological messages: Antibacterial molecules targeting nucleic acids during interbacterial conflicts.

Bacteria live in polymicrobial communities and constantly compete for resources. These organisms have evolved an array of antibacterial weapons to inhibit the growth or kill competitors. The arsenal comprises antibiotics, bacteriocins, and contact-dependent effectors that are either secreted in the medium or directly translocated into target cells. During bacterial antagonistic encounters, several cellular components important for life become a weak spot prone to an attack. Nucleic acids and the machinery responsible for their synthesis are well conserved across the tree of life. These molecules are part of the information flow in the central dogma of molecular biology and mediate long- and short-term storage for genetic information. The aim of this review is to summarize the diversity of antibacterial molecules that target nucleic acids during antagonistic interbacterial encounters and discuss their potential to promote the emergence antibiotic resistance.

Antibacterial T6SS effectors with a VRR-Nuc domain are structure-specific nucleases.

The type VI secretion system (T6SS) secretes antibacterial effectors into target competitors. Salmonella spp. encode five phylogenetically distinct T6SSs. Here, we characterize the function of the SPI-22 T6SS of Salmonella bongori showing that it has antibacterial activity and identify a group of antibacterial T6SS effectors (TseV1-4) containing an N-terminal PAAR-like domain and a C-terminal VRR-Nuc domain encoded next to cognate immunity proteins with a DUF3396 domain (TsiV1-4). TseV2 and TseV3 are toxic when expressed in Escherichia coli and bacterial competition assays confirm that TseV2 and TseV3 are secreted by the SPI-22 T6SS. Phylogenetic analysis reveals that TseV1-4 are evolutionarily related to enzymes involved in DNA repair. TseV3 recognizes specific DNA structures and preferentially cleave splayed arms, generating DNA double-strand breaks and inducing the SOS response in target cells. The crystal structure of the TseV3:TsiV3 complex reveals that the immunity protein likely blocks the effector interaction with the DNA substrate. These results expand our knowledge on the function of Salmonella pathogenicity islands, the evolution of toxins used in biological conflicts, and the endogenous mechanisms regulating the activity of these toxins.

Revisiting the steps of Salmonella gut infection with a focus on antagonistic interbacterial interactions.

A commensal microbial community is established in the mammalian gut during its development, and these organisms protect the host against pathogenic invaders. The hallmark of noninvasive Salmonella gut infection is the induction of inflammation via effector proteins secreted by the type III secretion system, which modulate host responses to create a new niche in which the pathogen can overcome the colonization resistance imposed by the microbiota. Several studies have shown that endogenous microbes are important to control Salmonella infection by competing for resources. However, there is limited information about antimicrobial mechanisms used by commensals and pathogens during these in vivo disputes for niche control. This review aims to revisit the steps that Salmonella needs to overcome during gut colonization-before and after the induction of inflammation-to achieve an effective infection. We focus on a series of reported and hypothetical antagonistic interbacterial interactions in which both contact-independent and contact-dependent mechanisms might define the outcome of the infection.

Targeting the Achilles' Heel of Bacteria: Different Mechanisms To Break Down the Peptidoglycan Cell Wall during Bacterial Warfare.

Bacteria commonly live in dense polymicrobial communities and compete for scarce resources. Consequently, they employ a diverse array of mechanisms to harm, inhibit, and kill their competitors. The cell wall is essential for bacterial survival by providing mechanical strength to resist osmotic stress. Because peptidoglycan is the major component of the cell wall and its synthesis is a complex multistep pathway that requires the coordinate action of several enzymes, it provides a target for rival bacteria, which have developed a large arsenal of antibacterial molecules to attack the peptidoglycan of competitors. These molecules include antibiotics, bacteriocins, and contact-dependent effectors that are either secreted into the medium or directly translocated into a target cell. In this minireview, we summarize the diversity of these molecules and highlight distinct mechanisms to disrupt the peptidoglycan, giving special attention to molecules that are known or have the potential to be used during interbacterial competitions.