Genetic and physiological studies of the CiaH-CiaR two-component signal-transducing system involved in cefotaxime resistance and competence of Streptococcus pneumoniae

Giammarinaro, Philippe; Sicard, Michel; Gasc, Anne-Marie

doi:10.1099/13500872-145-8-1859

Cited by 62 publications

(72 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5c), and similar results have been described previously (10). The R6ciaR null mutant grew to different cell densities depending on the choline concentration in the medium without changes in generation time, similar to the R6 strain ( Fig.…”

Section: Fig 3 Effect Of Ciahsupporting

confidence: 74%

“…Surprisingly, this transformant was completely noncompetent, documenting that this particular ciaH allele conferred competence deficiency as well (10,14,18). The P230 mutation in CiaH was later shown by genomic transcription analysis to activate the CiaRH system and was hence referred to as ON mutation (36).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to the initial observations that mutations in the histidine kinase CiaH cause changes in susceptibility to cefotaxime and interfere with genetic competence (14), the CiaRH system contributes to autolysis in complex media (6,10,18,30,36), DOCmediated lysis (10), and thermotolerance and oxidative stress tolerance (8,22) and affects pneumococcal virulence in vivo in mouse infection models (34,44,48). The present analysis has extended cia-mediated effects to a whole battery of conditions that are related to cellular lysis: inhibition of early and late stages of peptidoglycan biosynthesis by antibiotics and prevention of teichoic acid biosynthesis by depletion of choline in the growth medium.…”

Section: Discussionmentioning

confidence: 99%

“…One of the genes controlled by CiaR, the protease/chaperone HtrA, has recently been analyzed in detail and appears to be the main mediator of the virulence phenotype and competence inhibition of cia mutants (21,22,44,45). Furthermore, increased autolysis of ciaR mutant cells has been observed under many conditions, including stationary-phase lysis and lysis triggered by deoxycholate or upon addition of CSP (6,10,18,30).…”

mentioning

confidence: 99%

“…A point mutation in CiaR reverted the competence-negative phenotype of the ciaH ON mutation completely (10), and consequently, loss-of-function ciaR mutants have been shown to be competent (8,15,35), suggesting that the CiaRH system controls directly or indirectly genetic competence.…”

mentioning

confidence: 99%

See 4 more Smart Citations

The CiaRH System ofStreptococcus pneumoniaePrevents Lysis during Stress Induced by Treatment with Cell Wall Inhibitors and by Mutations inpbp2xInvolved in β-Lactam Resistance

et al. 2006

View full text Add to dashboard Cite

The two-component signal-transducing system CiaRH of Streptococcus pneumoniae plays an important role during the development of beta-lactam resistance in laboratory mutants. We show here that a functional CiaRH system is required for survival under many different lysis-inducing conditions. Mutants with an activated CiaRH system were highly resistant to lysis induced by a wide variety of early and late cell wall inhibitors, such as cycloserine, bacitracin, and vancomycin, and were also less susceptible to these drugs. In contrast, loss-of-function CiaRH mutants were hypersusceptible to these drugs and were apparently unable to maintain a stationary growth phase in normal growth medium and under choline deprivation as well. Moreover, disruption of CiaR in penicillin-resistant mutants with an altered pbp2x gene encoding low-affinity PBP2x resulted in severe growth defects and rapid lysis. This phenotype was observed with pbp2x genes containing point mutations selected in the laboratory and with highly altered mosaic pbp2x genes from penicillin-resistant clinical isolates as well. This documents for the first time that PBP2x mutations required for development of beta-lactam resistance are functionally not neutral and are tolerated only in the presence of the CiaRH system. This might explain why cia mutations have not been observed in penicillin-resistant clinical isolates. The results document that the CiaRH system is required for maintenance of the stationary growth phase and for prevention of autolysis triggered under many different conditions, suggesting a major role for this system in ensuring cell wall integrity.

show abstract

Section: Fig 3 Effect Of Ciahsupporting

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The CiaRH System ofStreptococcus pneumoniaePrevents Lysis during Stress Induced by Treatment with Cell Wall Inhibitors and by Mutations inpbp2xInvolved in β-Lactam Resistance

et al. 2006

View full text Add to dashboard Cite

show abstract

Screening for Compounds That Affect the Interaction Between Bacterial Two-Component Signal Transduction Response Regulator Protein and Cognate Promoter DNA

Erickson¹,

Ulijasz²,

Weisblum³

2008

Methods in Molecular Medicine™

View full text Add to dashboard Cite

Bacterial signal transduction systems can be used as drug targets. The signal transduction targets fall into two groups--sensor kinases and response regulators. Previously reported studies describe hits that were thought to inactivate sensor kinases but on closer examination were found to act elsewhere instead; a possible reason for this is that full-length sensor kinases are integral membrane proteins whose activity might reflect interaction with the cell membrane or with membrane components. We describe a model system that instead is based on the interaction between a test compound and a response regulator in a homogeneous phase reaction. In this system, response regulator-DNA complex formation and its inhibition by a test compound are measured by fluorescence polarization. The model system should be readily adaptable to drug discovery based on other bacterial two-component s transduction systems.

show abstract

Calcium Regulation of Bacterial Virulence

King

Kayastha

Franklin

et al. 2019

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Genetic and physiological studies of the CiaH-CiaR two-component signal-transducing system involved in cefotaxime resistance and competence of Streptococcus pneumoniae

Cited by 62 publications

References 38 publications

The CiaRH System ofStreptococcus pneumoniaePrevents Lysis during Stress Induced by Treatment with Cell Wall Inhibitors and by Mutations inpbp2xInvolved in β-Lactam Resistance

The CiaRH System ofStreptococcus pneumoniaePrevents Lysis during Stress Induced by Treatment with Cell Wall Inhibitors and by Mutations inpbp2xInvolved in β-Lactam Resistance

Screening for Compounds That Affect the Interaction Between Bacterial Two-Component Signal Transduction Response Regulator Protein and Cognate Promoter DNA

Calcium Regulation of Bacterial Virulence

Contact Info

Product

Resources

About