A trans -acting leader RNA from a Salmonella virulence gene

Abstract

Bacteria use flagella to move toward nutrients, find its host, or retract from toxic substances. Because bacterial flagellum is one of the ligands that activate the host innate immune system, its synthesis should be tightly regulated during host infection, which is largely unknown. Here, we report that a bacterial leader mRNA from the virulence operon in the intracellular pathogen serovar Typhimurium binds to the coding region of mRNAs in the operon encoding the FljB phase 2 flagellin, a main component of bacterial flagella and the FljA repressor for the FliC phase 1 flagellin, and degrades mRNAs in an RNase E-dependent fashion during infection. A nucleotide substitution of the flagellin gene that prevents the leader RNA-mediated down-regulation increases the-encoded flagellin synthesis, leading to a hypermotile phenotype inside macrophages. Moreover, the nucleotide substitution renders hypervirulent, indicating that FljB-based motility must be compromised in the phagosomal compartment where resides. This suggests that this pathogen promotes pathogenicity by producing a virulence protein and limits locomotion by a-acting leader RNA from the same virulence gene during infection.

A Family of Small Intrinsically Disordered Proteins Involved in Flagellum-Dependent Motility in Salmonella enterica

“…Flagella also play important roles in Salmonella pathogenesis. For example, flagellum-dependent motility promotes efficient colonization by Salmonella cells in the intestine (7) and invasion into intestinal epithelial cells (8); Salmonella mutants defective in flagellum expression are attenuated in both survival inside macrophages (9)(10)(11) and virulence in murine models of infection (10). Moreover, flagella mediate the attachment of Salmonella cells to cholesterol to initiate biofilm formation (12), and hyperflagellated swarming cells exhibit enhanced resistance to a broad range of antibiotics (13).…”

Elongation factor P controls translation of the mgtA gene encoding a Mg2+ transporter during Salmonella infection

“…Does it have a potential role for the mgtA transcripts independent of producing the MgtA proteins? In addition to a previous example (Loh et al, 2009), a recent study may provide a clue for a potential role for the mgtA transcripts because one of the small leader transcripts of the mgtCBR operon is highly expressed inside macrophages and functions as a trans-acting riboregulator for downregulating synthesis of the Salmonella flagellin protein during infection (Choi, Han, Cho, Nam, & Lee, 2017). Therefore, a future exploration seeking a potential role(s) of the mgtA transcripts independent of its protein functions is expected.…”

Genetic variation in the MacAB-TolC efflux pump influences pathogenesis of invasive Salmonella isolates from Africa

“…Long 5’-UTRs have been shown to have trans-acting regulatory roles in expression of virulence genes in both S . Typhimurium [ 43 , 85 ] and S . Typhi [ 42 ].…”

“…The mapped transcriptional start site (TSS) of macA is 504 nucleotides upstream of the start codon and is located within the divergently-transcribed gene ybjX (also known as somA) (see Fig 1B and https://tinyurl.com/macAB-Jbrowse). Long 5'-UTRs have been shown to have trans-acting regulatory roles in expression of virulence genes in both S. Typhimurium [43,85] and S. Typhi [42]. Such 5'-UTR elements can post-transcriptionally regulate gene expression through formation of RNA secondary structures that control interactions with small regulatory RNAs, or by directly influencing transcript stability [86].…”