The LetA‐RsmYZ‐CsrA regulatory cascade, together with RpoS and PmrA, post‐transcriptionally regulates stationary phase activation of Legionella pneumophila Icm/Dot effectors | Semantic Scholar (2024)

A single‐domain response regulator (SDRR) is identified, named LerC, which functions as a connector protein between the PmrAB and the LetAS TCSs, suggesting that members of this widespread group of proteins might function as connector proteins in other bacterial regulatory networks.

The results show that CpxR plays a major role in L. pneumophila pathogenesis gene expression and functions as part of a regulatory network.

Results demonstrate that several of the L. pneumophila effectors which are coregulated in the bacterial cell are involved in the modulation of the same eukaryotic pathway.

A unique regulatory mode of CsrA is identified, the active stabilization of RNA anti-terminator conformations inside a coding sequence preventing Rho-dependent termination of the gap operon through transcriptional polarity effects.

LelA represents a novel type of Legionella effector regulator, which coordinates the expression of both adjacently and distantly located effector‐encoding genes, thus forming small groups of co‐regulated effectors.

Examples of interplay between these TCSs were already reported indicating that they form part of a regulatory network that orchestrates the expression of L. pneumophila effector-encoding genes during infection.

Since all known ICEs of legionellae encode coinherited csrA-type IV secretion system pairs, it is predicted that CsrA superfamily proteins regulate ICE activity to increase their horizontal spread, thereby expanding L. pneumophila versatility.

Results demonstrate for the first time that two of the three L. pneumophila Fis regulators directly repress the expression of Icm/Dot effector-encoding genes.

A novel L. pneumophila genomic island is described, which undergoes horizontal gene transfer within the Legionella genus and encodes two Icm/Dot effectors: LegK3 and a previously uncharacterized effector the authors named CegK3, as well as a LuxR type regulator, which is named RegK3.

It is postulated that the letS(T311M) mutant may relay phosphate less efficiently than the WT LetS sensor protein, leading to sluggish gene expression and a variety of phenotypic profiles, which likely confers versatility as microbes adapt to fluctuating environments.

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The results establish the PmrA regulator as a fundamental regulator of the icm/dot type IV secretion system in these two bacteria.

The results establish that the CpxR regulator is a fundamental regulator of the icm/dot type IV secretion system in L. pneumophila.

It is demonstrated that, during replication in broth, CsrA represses every post‐exponential phase phenotype examined, including cell shape shortening, motility, pigmentation, stress resistance, sodium sensitivity, cytotoxicity and efficient macrophage infection.

The data support a model in which RpoS co‐operates with other regulators to induce L. pneumophila virulence in the PE phase, and support the hypothesis that a stringent response mechanism regulates L.'s virulence.

Two small, untranslated RNAs, RsmY and RsmZ, are key factors that relieve RsmA‐mediated regulation of secondary metabolism and biocontrol traits in the GacS/GacA cascade of strain CHA0.

Together, the data indicate that, as the nutrient supply wanes, ppGpp triggers a regulatory cascade mediated by LetA/ LetS, RpoS, FliA and letE that coordinates differentiation of replicating L. pneumophila to a transmissible form.

This study presents the first evidence for a direct regulator (CpxR) of an icm-dot virulence gene (icmR) and suggests that this regulator together with other regulatory factors probably concerts with the expression of icm and dot genes to result in successful infection.

Evidence is provided that the pgaABCD transcript, required for the synthesis of the polysaccharide adhesin PGA of Escherichia coli, is the key target of biofilm regulation by CsrA.

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