Biology subjects

Righi, L.

Publications and source records attributed to Righi, L..

3 recordsLinked to original sources

bioRxiv2025

Structure and Activation Mechanism of a Lamassu Phage Defence System

Lamassu is a diverse family of defence systems that protect bacteria, including pandemic strains of Vibrio cholerae, against phage infection. They target essential cellular processes, aborting infection and preventing phage propagation by terminating the infected host. The mechanisms by which Lamassu efectors are activated when needed and otherwise suppressed are unknown. Here, we present structures of a Lamassu defence system from Salmonella enterica. We show that an oligomerization domain of the nuclease efector, LmuA, is sequestered by two tightly-folded SMC-like LmuB protomers and LmuC. Upon activation, liberated LmuA proteins assemble into a cyclic homo-tetramer, in which two of four nuclease domains are brought into proximity to create an active site capable of cleaving DNA. We propose tetramer formation is likely a one-way switch that establishes a threshold to limit potential spontaneous activation and cell death. Our findings reveal a mechanism of cellular defence, involving liberation and oligomerization of immune efectors, and shed light on how Lamassu systems balance potent immune responses with self-preservation.

microbiology↗

bioRxiv2024

Diverse phage defence systems define West African South American pandemic Vibrio cholerae

Our understanding of the factors underlying the evolutionary success of different lineages of pandemic Vibrio cholerae remains incomplete. Interestingly, two unique genetic signatures define the West African South American (WASA) lineage of V. cholerae responsible for the 1991-2001 Latin American cholera epidemic. Here we show these signatures encode diverse anti-phage defence systems. Firstly, the WASA-1 prophage encodes a 2-gene abortive-infection system WonAB that renders the lineage resistant to the major predatory vibriophage ICP1, which alongside other phages, is thought to restrict cholera epidemics and has potential for use in prophylaxis. Secondly, a unique set of genes on the Vibrio seventh pandemic island II encodes an unusual modification-dependent restriction system targeting phages with modified genomes, and a new member of the Shedu defence family that defends against vibriophage X29. Taken together, we propose that these anti-phage defence systems have likely contributed to the success of a major epidemic lineage of the ongoing seventh cholera pandemic.

microbiology↗

bioRxiv2024

Molecular mechanism of plasmid elimination by the DdmDE defense system

Seventh pandemic Vibrio cholerae strains contain two hallmark pathogenicity islands that encode the DNA defense modules DdmABC and DdmDE. Here we use cryo-EM to reveal the mechanistic basis for plasmid defense by DdmDE. A cryo-EM structure of the DdmD helicase-nuclease reveals that it adopts an auto-inhibited dimeric architecture. The prokaryotic Argonaute protein DdmE uses a DNA guide to target plasmid DNA. A structure of the DdmDE complex, validated by in vivo mutational studies, shows that DNA binding by DdmE triggers disassembly of the DdmD dimer and loading of monomeric DdmD onto the non-target DNA strand. Finally, in vitro studies reveal that DdmD translocates in the 5 to 3 direction, while partially degrading the plasmid DNA. These findings provide critical insights into the architecture and mechanism of DdmDE systems in plasmid elimination.

microbiology↗