Transcriptomic and Phenotypic Analyses Identify Coregulated, Overlapping Regulons among PrfA, CtsR, HrcA, and the Alternative Sigma Factors σ ^B , σ ^C , σ ^H , and σ ^L in Listeria monocytogenes

Abstract

A set of seven Listeria monocytogenes 10403S mutant strains, each bearing an in-frame null mutation in a gene encoding a key regulatory protein, was used to characterize transcriptional networks in L. , and at least one additional regulator). Comparative phenotypic characterization measuring acid resistance, heat resistance, intracellular growth in J774 cells, invasion into Caco-2 epithelial cells, and virulence in the guinea pig model indicated contributions of (i)B to acid resistance, (ii) CtsR to heat resistance, and (iii) PrfA, B , and CtsR to virulence-associated characteristics. Loss of the remaining transcriptional regulators (i.e., sigH, sigL, or sigC) resulted in limited phenotypic consequences associated with stress survival and virulence. Identification of overlaps among the regulons provides strong evidence supporting the existence of complex regulatory networks that appear to provide the cell with regulatory redundancies, along with the ability to fine-tune gene expression in response to rapidly changing environmental conditions.

The arsenal of virulence factors deployed byListeria monocytogenesto promote its cell infection cycle

“…In particular, PrfA and σ B were shown to jointly contribute to processes like intracellular growth and virulence. [200][201][202] Indeed, several virulence factors appeared under the control of one or even both of these transcriptional regulators (Fig. 2).…”

Listeria monocytogenes σHContributes to Expression of Competence Genes and Intracellular Growth

“…1). Although transcriptome analysis did not detect any competence genes in its regulon (4,6), this observation implies that H may be involved in the expression of comG and comE. H can express comE and comG operons.…”

“…contains another sigma factor, most likely the housekeeping A (rpoD), because consensus sequences for B (40) and L (4) could not be found ( C controls few genes [4,6], and there is no reported consensus sequence). Therefore, comF expression in L. monocytogenes resembles B. subtilis regulation, in which comF expression is regulated by A and enhanced by ComK (18,41).…”

“…Transcriptomic and proteomic analyses have found an overlap between the regulons and cross connections between regulators, suggesting a complex mechanism for the fine-tuning of stress responses in L. monocytogenes (4)(5)(6).…”

“…Leaving aside the main stress sigma factor ( B ), H positively regulates the largest number of genes and overlaps with other regulons, particularly B (4,6). It is expected that the function of H in L. monocytogenes is complex and not directly linked to one specific process.…”