Publications by authors named "Alexander M J Hall"

Toxin-antitoxin (TA) systems allow bacteria to adapt to changing environments without altering gene expression. Despite being overrepresented in Mycobacterium tuberculosis, their physiological roles remain elusive. We describe a TA system in M.

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Article Synopsis
  • Type II toxin-antitoxin (TA) systems are two-gene modules found in many prokaryotes, with GNAT toxins and DUF1778 antitoxins being key examples.
  • GNAT toxins disrupt cell growth by interfering with translation through the acetylation of aminoacyl-tRNAs, primarily targeting Gly-tRNA isoacceptors.
  • The study reveals that the ancestor of GNAT toxins likely had broader specificity, capable of acetylating multiple elongator tRNAs, highlighting significant evolutionary changes in substrate specificity over time.
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Toxin-antitoxin (TA) systems are a large family of genes implicated in the regulation of bacterial growth and its arrest in response to attacks. These systems encode nonsecreted toxins and antitoxins that specifically pair, even when present in several paralogous copies per genome. Salmonella enterica serovar Typhimurium contains three paralogous TacAT systems that block bacterial translation.

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Type IV pili (Tfp) are functionally versatile filaments, widespread in prokaryotes, that belong to a large class of filamentous nanomachines known as type IV filaments (Tff). Although Tfp have been extensively studied in several Gram-negative pathogens where they function as key virulence factors, many aspects of their biology remain poorly understood. Here, we performed a global biochemical and structural analysis of Tfp in a recently emerged Gram-positive model, In particular, we focused on the five pilins and pilin-like proteins involved in Tfp biology in We found that the two major pilins, PilE1 and PilE2, (i) follow widely conserved principles for processing by the prepilin peptidase PilD and for assembly into filaments; (ii) display only one of the post-translational modifications frequently found in pilins, a methylated N terminus; (iii) are found in the same heteropolymeric filaments; and (iv) are not functionally equivalent.

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Streptococcus sanguinis, a naturally competent opportunistic human pathogen, is a Gram-positive workhorse for genomics. It has recently emerged as a model for the study of type IV pili (Tfp)-exceptionally widespread and important prokaryotic filaments. To enhance genetic manipulation of Streptococcus sanguinis, we have developed a cloning-independent methodology, which uses a counterselectable marker and allows sophisticated markerless gene editing in situ.

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