Versatility and Complexity: Common and Uncommon Facets of LysR-Type Transcriptional Regulators

Abstract

LysR-type transcriptional regulators (LTTRs) form one of the largest families of bacterial regulators. They are widely distributed and contribute to all aspects of metabolism and physiology. Most are homotetramers, with each subunit composed of an N-terminal DNA-binding domain followed by a long helix connecting to an effector-binding domain. LTTRs typically bind DNA in the presence or absence of a small-molecule ligand (effector). In response to cellular signals, conformational changes alter DNA interactions, contact with RNA polymerase, and sometimes contact with other proteins. Many are dual-function repressor–activators, although different modes of regulation may occur at multiple promoters. This review presents an update on the molecular basis of regulation, the complexity of regulatory schemes, and applications in biotechnology and medicine. The abundance of LTTRs reflects their versatility and importance. While a single regulatory model cannot describe all family members, a comparison of similarities and differences provides a framework for future study. Expected final online publication date for the Annual Review of Microbiology, Volume 77 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Auxin-mediated regulation of susceptibility to toxic metabolites, c-di-GMP levels, and phage infection in the rhizobacterium Serratia plymuthica

“…LTTR family members typically consist of a N-terminal DNA-binding domain and a C-terminal ligand-binding domain (LBD). Typically, ligand binding modulates the regulatory activity of LTTRs ( 49 ). Previous data in E. coli revealed that 4HBA, salicylate, and benzoate induce aaeXAB expression ( 45 ).…”

The LysR‐type transcription factor LsrB regulates beta‐lactam resistance in Agrobacterium tumefaciens

“…Given the large impact of LsrB on beta‐lactam resistance by directly modulating the levels of the anhydroamidase AmpD, we wondered how LsrB itself is regulated. A hallmark of LysR‐type transcription factors is their autoregulation (Baugh et al., 2023; Maddocks & Oyston, 2008). In Rhizobiaceae , including Agrobacterium , LsrB is encoded in a conserved operon downstream of trxB coding for a thioredoxin reductase (Budnick et al., 2020; Eisfeld et al., 2021; Luo et al., 2005; Sheehan et al., 2015; Sheehan & Caswell, 2018).…”

“…This finding suggests that the bidirectional promoter shared by ampC and ampR is regulated by AmpR itself. This type of autoregulation is very common for LysR‐type transcription factors (Baugh et al., 2023; Maddocks & Oyston, 2008).…”

Relevance of the Adjuvant Effect between Cellular Homeostasis and Resistance to Antibiotics in Gram-Negative Bacteria with Pathogenic Capacity: A Study of Klebsiella pneumoniae

“…The diversity and complexity of LTTRs in K. pneumoniae highlight their importance in adapting and surviving in different environments, including their ability to colonize and infect humans. Proteins bind to specific regions of DNA known as regulator binding sites (RBSs) and can function as either activators or repressors of gene transcription [ 148 ]. A study conducted in K. pneumoniae investigated the Type VI Secretion System (T6SS) factor, which is associated with cell invasion, competition, and colonization processes.…”