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Lallement, C.

Publications and source records attributed to Lallement, C..

2 recordsLinked to original sources

The bacterial SOS response promotes the expression of the transposase encoded by ISCR mobile genetic elements

Insertion sequences (IS) are widely involved in bacterial genomic plasticity by disrupting, adding, moving genomic sequences, or by activating or extinguishing gene expression. A specific family of IS, ISCR (for insertion sequence of Common Region), is thought to be involved in the dissemination of antibiotic resistance genes (ARG). While some ISCR members are commonly found in bacteria isolated in clinical settings and can contribute to downstream ARG expression, the mechanisms regulating the ISCR-encoded transposases expression have remained uncharacterized. Here, we investigated the expression of the transposase gene of ISCR1, ISCR2 and ISCR8, and its regulation in Escherichia coli. Using in silico analyses and in vitro experiments, we showed that expression levels were extremely low, as observed for most IS transposases. We further demonstrated the direct role of DNA damages and the key SOS response repressor, LexA, in controlling the activity of transposase promoter. These results provide evidence that the mobility of at least some ISCR elements may be promoted upon bacterial exposure to antibiotics inducing the SOS response. IMPORTANCEMobile genetic elements are the most prevalent cause of antibiotic resistance emergence. Among these mobile elements, insertion sequences (IS) are well known to allow the dissemination of antibiotic resistance genes through the action of their tranposase. Here, we studied the regulation of the transposase expression in a specific family of IS, the ISCR family, some members of which are known to be involved in antibiotic resistance. Characterizing the regulation of transposase expression is an important starting point for understanding how these IS can contribute, through their movement, to the spread and expression of antibiotic resistance. This knowledge is necessary if we are to hope to prevent this spread one day.

microbiology↗

Stress-Induced Iron-Sulfur Cluster Damage as a Conserved Trigger of the Stringent Response

Pathogenic bacteria rely on the stringent response to adapt to the complex and fluctuating conditions encountered within the host. However, the mechanisms by which the stringent response senses host-induced stress remain poorly understood. Here, we identify iron-sulfur (Fe-S) cluster damage as a conserved trigger of the stringent response in major Gram-negative pathogens, including Salmonella enterica, Enterobacter cloacae, and Klebsiella pneumoniae. We demonstrate that Fe-S cluster disruption--caused by oxidative stress or metal imbalance--restricts the intracellular pools of sulfur-containing and branched-chain amino acids, thereby activating the ribosome-associated (p)ppGpp synthetase RelA. Furthermore, we show that iron availability governs recovery from Fe-S cluster damage, modulating the dynamics of the stringent response. Finally, we emphasize the dual role of (p)ppGpp in transcriptional regulation, enhancing bacterial fitness during Fe-S cluster stress while simultaneously promoting virulence by upregulating the SPI-2 type III secretion system. Together, these findings uncover a conserved mechanism by which pathogenic bacteria integrate metabolic stress into adaptive gene regulation and virulence, positioning Fe-S cluster integrity as a pivotal node linking environmental sensing to transcriptional control during infection.

microbiology↗