The algR gene, which regulates mucoidy in Pseudomonas aeruginosa, belongs to a class of environmentally responsive genes

Deretić, Vojo; Dikshit, Rashmi; Konyecsni, W M; Chakrabarty, Ananda M.; Misra, Tapan K.

doi:10.1128/jb.171.3.1278-1283.1989

Cited by 214 publications

(165 citation statements)

References 41 publications

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“…We therefore reproduced the mucoid phenotype in our P. aeruginosa strains by transformation with the multicopy vector pUCPKS containing algU (pUCPalgU). Under these conditions we confirmed that the algR mutant S39 is severely reduced in alginate production (Table 1), in agreement with previous studies in mucoid P. (19,32,34). However, under these conditions, the fimS mutant S62 still produces large amounts of alginate similar to the control (Table 1).…”

Section: Resultssupporting

confidence: 81%

“…As a consequence, studies on the regulation of alginate production have been carried out largely in variants selected for the stable expression of mucoidy (3,19,30,32). Such variants have been subsequently shown to contain mutations in the anti-sigma factors algN or mucA (which suppress the sigma factor AlgU) and thus result in upregulation of AlgU activity (2,3,33).…”

Section: Resultsmentioning

confidence: 99%

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The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

Whitchurch

Alm

Mattick

1996

Proc. Natl. Acad. Sci. U.S.A.

133

153

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Mucoid strains of Pseudomonas aeruginosa isolated from the lungs of cystic fibrosis patients produce large amounts of the exopolysaccharide alginate. AlgR has long been considered a key regulator of alginate production, but its cognate sensor has not been identified. Here we show that AlgR is required for twitching motility, which is a form ofbacterial surface translocation mediated by type 4 fimbriae. Adjacent to algR we have identified a sensor gene (fimS), which is also required for twitching motility. However, FimS does not appear to be required for alginate production in mucoid strains. FimS and AlgR are representative of a new subclass of two-component transmitter-receiver regulatory systems. The alternative sigma factor AlgU also affects both alginate production and twitching motility. Therefore, these two virulence determinants appear to be closely associated and coordinately regulated.Pseudomonas aeruginosa is an opportunistic pathogen of humans and other species (1). It causes severe chronic infections in patients who are immunocompromised as a result of cancer chemotherapy or AIDS, or who are suffering from burns or cystic fibrosis. It produces an extensive suite of virulence factors including extracellular proteases and toxins, lipases, pyochelins, exopolysaccharides, and type 4 fimbriae. In cystic fibrosis, P. aeruginosa produces recurrent and chronic lung infections, which impose substantial morbidity and often mortality as a consequence of accumulated damage to the lung. Isolates from such chronic infections exhibit a "mucoid" colony phenotype due to the production of large amounts of the exopolysaccharide alginate, apparently as a means of evading immune responses (for reviews see refs. 2 and 3).

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

Whitchurch

Alm

Mattick

1996

Proc. Natl. Acad. Sci. U.S.A.

133

153

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“…The mechanism for enhanced alg expression caused by Ca 2ϩ addition is not known. However, the results suggest that a Ca 2ϩ -controlled factor(s) may be involved in alg gene regulation, either through a previously identified regulator, such as one of the two-component sensory systems known to be involved in alg regulation (9,22,70), or through another regulatory factor that has not yet been identified. In biofilms, Ca 2ϩ may play an additional role in the observed increase in biofilm thickness by ionic cross-linking and gelling of the uronic acid residues, thereby modifying the biofilm architecture.…”

Section: Discussionmentioning

confidence: 54%

Calcium-Induced Virulence Factors Associated with the Extracellular Matrix of MucoidPseudomonas aeruginosaBiofilms

Sarkisova¹,

Patrauchan

Berglund³

et al. 2005

J Bacteriol

197

173

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Pseudomonas aeruginosa colonizes the pulmonary tissue of patients with cystic fibrosis (CF), leading to biofilm-associated infections. The pulmonary fluid of CF patients usually contains elevated concentrations of cations and may contain the P. aeruginosa redox-active pigment pyocyanin, which is known to disrupt calcium homeostasis of host cells. Since divalent cations are important bridging ions for bacterial polysaccharides and since they may play regulatory roles in bacterial gene expression, we investigated the effect of calcium ions on the extracellular matrix constituents of P. aeruginosa biofilms. For mucoid strain P. aeruginosa FRD1, calcium addition (1.0 and 10 mM as CaCl 2 ) resulted in biofilms that were at least 10-fold thicker than biofilms without added calcium. Scanning confocal laser microscopy showed increased spacing between cells for the thick biofilms, and Fourier transform infrared spectroscopy revealed that the material between cells is primarily alginate. An algD transcriptional reporter demonstrated that calcium addition caused an eightfold increase in alg gene expression in FRD1 biofilms. Calcium addition also resulted in increased amounts of three extracellular proteases (AprA, LasB, and PrpL). Immunoblots of the biofilm extracellular material established that AprA was harbored within the biofilm extracellular matrix. An aprA deletion mutation and a mutation in gene for a putative P. aeruginosa calmodulin-like protein did not significantly affect calcium-induced biofilm structure. Two-dimensional gel electrophoresis showed increased amounts of phenazine biosynthetic proteins in FRD1 biofilms and in calcium-amended planktonic cultures. Spectrochemical analyses showed that the calcium addition causes a three-to fivefold increase in pyocyanin production. These results demonstrate that calcium addition affects the structure and extracellular matrix composition of mucoid P. aeruginosa biofilms, through increased expression and stability of bacterial extracellular products. The calcium-induced extracellular matrix of mucoid P. aeruginosa consists primarily of the virulence factor alginate and also harbors extracellular proteases and perhaps pyocyanin, a biomolecule that may further disrupt cellular calcium levels.

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“…biosynthesis requires activation of the alternative sigma factor AlgU (12,13) and the two-component transcriptional regulator AlgR (12,14,15). Two-component signal transduction systems are important in regulating the bacterial response to environmental conditions.…”

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confidence: 99%

The Pseudomonas aeruginosa Two-Component Regulator AlgR Directly Activates rsmA Expression in a Phosphorylation-Independent Manner

2017

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Pseudomonas aeruginosa is an important pathogen of the immunocompromised, causing both acute and chronic infections. In cystic fibrosis (CF) patients, P. aeruginosa causes chronic disease. The impressive sensory network of P. aeruginosa allows the bacterium to sense and respond to a variety of stimuli found in diverse environments. Transcriptional regulators, including alternative sigma factors and response regulators, integrate signals changing gene expression, allowing P. aeruginosa to cause infection. The two-component transcriptional regulator AlgR is important in P. aeruginosa pathogenesis in both acute and chronic infections. In chronic infections, AlgR and the alternative sigma factor AlgU activate the genes responsible for alginate production. Previous work demonstrated that AlgU controls rsmA expression. RsmA is a posttranscriptional regulator that is antagonized by two small RNAs, RsmY and RsmZ. In this work, we demonstrate that AlgR directly activates rsmA expression from the same promoter as AlgU. In addition, phosphorylation was not necessary for AlgR activation of rsmA using algR and algZ mutant strains. AlgU and AlgR appear to affect the antagonizing small RNAs rsmY and rsmZ indirectly. RsmA was active in a mucA22 mutant strain using leader fusions of two RsmA targets, tssA1 and hcnA. AlgU and AlgR were necessary for posttranscriptional regulation of tssA1 and hcnA. Altogether, our work demonstrates that the alginate regulators AlgU and AlgR are important in the control of the RsmA posttranscriptional regulatory system. These findings suggest that RsmA plays an unknown role in mucoid strains due to AlgU and AlgR activities.IMPORTANCE P. aeruginosa infections are difficult to treat and frequently cause significant mortality in CF patients. Understanding the mechanisms of persistence is important. Our work has demonstrated that the alginate regulatory system also significantly impacts the posttranscriptional regulator system RsmA/Y/Z. We demonstrate that AlgR directly activates rsmA expression, and this impacts the RsmA regulon. This leads to the possibility that the RsmA/Y/Z system plays a role in helping P. aeruginosa persist during chronic infection. In addition, this furthers our understanding of the reach of the alginate regulators AlgU and AlgR.KEYWORDS P. aeruginosa, RsmA, AlgR, mucoid, Pseudomonas aeruginosa, cystic fibrosis, mucA, two-component regulatory systems T he opportunistic pathogen Pseudomonas aeruginosa possesses multiple virulence factors for causing disease. This allows P. aeruginosa to cause both acute and chronic infections. Acute infecting strains are characterized by the presence of type IV pili (T4P), flagella, and a type III secretion system (T3SS) (1-3). In contrast, chronic infecting strains diversify (4, 5) and frequently do not express T3SS, T4P, or flagella (6, 7). Chronic infecting strains often form biofilms composed of exopolysaccharides, such as alginate, and signal a decline in lung function in CF patients (8-11). Alginate

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The algR gene, which regulates mucoidy in Pseudomonas aeruginosa, belongs to a class of environmentally responsive genes

Cited by 214 publications

References 41 publications

The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

Calcium-Induced Virulence Factors Associated with the Extracellular Matrix of MucoidPseudomonas aeruginosaBiofilms

The Pseudomonas aeruginosa Two-Component Regulator AlgR Directly Activates rsmA Expression in a Phosphorylation-Independent Manner

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