TpeX is identified as a bactericidal, colicin-like pore-forming T6SS effector whose membrane activity is controlled by a cognate immunity protein, thereby expanding the repertoire of membrane-targeting weapons used by P. aeruginosa in interbacterial competition.
Genetic analysis and structural modeling indicate that TseMt is delivered through a dedicated PAAR−VgrG−chaperone pathway, defining the structural basis, functional mechanism, and delivery pathway of the H4‐T6SS effector TseMt from a clinical P. aeruginosa isolate.
Pseudomonas aeruginosa is a nosocomial pathogenic bacterium that causes a wide range of human infectious diseases. The type III secretion system (T3SS) serves as a key virulence determinant underlying the pathogenesis of this bacterium in acute infections. As the master transcriptional activator of T3SS, ExsA binds to target promoter regions and modulates the expression of all currently identified T3SS genes. In this study, we identified tyrosine phosphoprotein A (TypA) as a repressor that restricts expression of the T3SS in P. aeruginosa. TypA interacts with ExsA to block its binding to target promoters, thereby inhibiting T3SS expression. We show that the typA expression is induced in response to low calcium, low temperature, a biofilm lifestyle, and direct contact with host cells. Additionally, the absence of TypA caused a growth defect in P. aeruginosa at low temperatures. Collectively, these data confirm the significant role of TypA and reveal a novel molecular mechanism by which P. aeruginosa regulates T3SS.
Li-Wen Yin, Yi-Ming Li, Xue-Tao Gong et al.· Microorganisms· 0 citations
The type VI secretion system (T6SS) is a contact-dependent bacterial weapon to inject hazardous proteins into competitors and can be pivotal for bacterial fitness. Throughout the lifecycle of Vibrio cholerae, beneficial and detrimental activities of the T6SS have been described, but its role in biofilm-associated interactions remains poorly understood. Here, we show that biofilm formation is accompanied by significant repression of T6SS genes. Expression analyses across multiple V. cholerae isolates revealed consistent downregulation of the major T6SS gene cluster in biofilm-derived cells relative to planktonic cultures. Consistent with this biofilm-dependent repression, a loss of the T6SS did not affect V. cholerae biofilm formation. Notably, biofilm-derived V. cholerae wild-type isolates and their isogenic T6SS-deletion mutants displayed comparable resistance to attacks by T6SS-reactive Pseudomonas aeruginosa. These findings suggest that T6SS repression during biofilm growth provides a fitness advantage for V. cholerae by limiting susceptibility to T6SS-mediated counterattacks from neighboring heterologous T6SS+ predatory species. Our results, therefore, identify conditional T6SS silencing as a potential adaptive strategy that promotes survival within multispecies microbial communities, particularly in environments containing bacteria with highly active or more potent T6SS machineries.
Stephan P. Ebenberger, J. Pombo, Alexander Rechberger et al.· Microorganisms· 0 citations
The extent to which chaperones are universally required for effector secretion is evaluated, through analysis of the conservation of chaperone sequence and structure, to discuss how these proteins interact with and support the secretion of diverse substrates.
Kyra Roepke, Alexia J Galsworthy, Adam Agbamu et al.· Microbiology· 0 citations
Abstract Bacterial type VI secretion systems (T6SSs) are molecular devices that traverse the bacterial envelope and mediate the translocation of protein effectors directly into prokaryotic or eukaryotic cells, thereby interfering with diverse cellular processes in target organisms. T6SSs involved in interbacterial competition have been widely described and functionally characterized, together with a remarkable arsenal of cognate toxins. In contrast, comparatively less is known about anti-eukaryotic T6SSs. This review summarizes recent advances in the study of T6SSs that target eukaryotic cells, highlighting their roles in virulence, resistance to environmental predators, and microbial competition. We discuss T6SS-mediated interactions with protozoan predators, fungi, animal hosts and plants, emphasizing the expanding repertoire of T6SS effectors that modulate conserved eukaryotic pathways. Together, these findings reveal the ecological and pathogenic relevance of T6SS-driven trans-kingdom interactions.
Izabella Santos Mori Bragil, Bianca B. Batista, José Felipe Teixeira da Silva Santos et al.· Genetics and Molecular Biolo...· 0 citations
Phages can modify host cell physiology to thwart competitors. The Pseudomonas aeruginosa-specific phage DMS3 encodes Aqs1, a protein inhibitor of type IV pilus (T4P) function to prevent host cell recognition by other phages that leverage these filaments for infection. Aqs1 disrupts T4P by binding to the hexameric ATPase PilB, required to power pilus filament extension, though several mechanistic details remain unclear. We show that Aqs1 has broad-spectrum activity and can disrupt T4P function in a variety of Gram negative bacteria. This protein inhibits PilB by binding to a solvent-exposed hydrophobic patch on the N2-domain, distal to the active site. Binding destabilizes the hexamer, preventing PilB accumulation at T4P machines. Aqs1 likely disrupts PilB oligomerization by displacing a flexible linker segment between the PilB N1- and N2-domains required for inter-subunit contact. Together, the Aqs1 mode of action provides a design template for broad-spectrum inhibitors of diverse bacterial virulence factors. Significance The phage-encoded protein Aqs1 disables type IV pilus (T4P) production in Pseudomonas aeruginosa by targeting the hexameric ATPase responsible for assembling pilus fibers. We show that despite originating from a P. aeruginosa-specific phage, Aqs1 can also disable T4 ATPase-dependent phenotypes across other pathogenic bacteria and homologous systems. Mechanistically, Aqs1 binds to a conserved patch on the PilB N2-domain away from the active site. Binding here breaks apart the PilB oligomer, preventing it from acting on T4P machines. Aqs1 binding at the N2-domain patch likely displaces a flexible PilB linker segment that binds to this site to stabilize the hexamer. Our work highlights a novel and conserved PilB allosteric site which is exploited by the phage-encoded protein Aqs1 to disrupt diverse T4 systems in multiple bacteria.
Nathan Roberge, Paankhi Dave, Véronique L. Taylor et al.· bioRxiv· 0 citations
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