Two-Component Signal Transduction Systems, Environmental Signals, and Virulence

Calva, Edmundo; Oropeza, Ricardo

doi:10.1007/s00248-005-0087-1

Cited by 67 publications

(65 citation statements)

References 87 publications

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“…These antagonists behave as competitive inhibitors of the regulator activity mediated by agonists. This finding is relevant to the development of inhibitors of TCS such as PhoP/Q of S. typhimurium (32,33), which were shown to be important virulence factors (6). A large number of inhibitors of different TCSs have been developed in vitro (34).…”

Section: Ortho-substitutions Of Toluene: Converting An Agonist Molecumentioning

confidence: 88%

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Bacterial sensor kinase TodS interacts with agonistic and antagonistic signals

Büsch

Lacal

Martos

et al. 2007

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

105

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The TodS/TodT two-component system controls expression of the toluene dioxygenase (TOD) pathway for the metabolism of toluene in Pseudomonas putida DOT-T1E. TodS is a sensor kinase that ultimately controls tod gene expression through its cognate response regulator, TodT. We used isothermal titration calorimetry to study the binding of different compounds to TodS and related these findings to their capacity to induce gene expression in vivo. Agonistic compounds bound to TodS and induced gene expression in vivo. Toluene was a powerful agonist, but ortho-substitutions of toluene reduced or abolished in vivo responses, although TodS recognized o-xylene with high affinity. These compounds were called antagonists. We show that agonists and antagonists compete for binding to TodS both in vitro and in vivo. The failure of antagonists to induce gene expression in vivo correlated with their inability to stimulate TodS autophosphorylation in vitro. We propose intramolecular TodS signal transmission, not molecular recognition of compounds by TodS, to be the phenomenon that determines whether a given compound will lead to activation of expression of the tod genes. Molecular modeling identified residues F46, I74, F79, and I114 as being potentially involved in the binding of effector molecules. Alanine substitution mutants of these residues reduced affinities (2-to 345-fold) for both agonistic and antagonistic compounds. Our data indicate that determining the inhibitory activity of antagonists is a potentially fruitful alternative to design specific two-component system inhibitors for the development of new drugs to inhibit processes regulated by two-component systems.histidine kinases ͉ isothermal titration calorimetry ͉ Pseudomonas ͉ two-component systems ͉ aromatic hydrocarbons

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Section: Ortho-substitutions Of Toluene: Converting An Agonist Molecumentioning

confidence: 88%

“…Their diversity is particularly pronounced in the input domain of HPKs and the output domain of RR, which were shown to belong to many different protein families (1). This variety ensures that HPKs recognize many different signals and RRs are involved in the regulation of different cellular processes (5)(6)(7).…”

mentioning

confidence: 99%

Bacterial sensor kinase TodS interacts with agonistic and antagonistic signals

Büsch

Lacal

Martos

et al. 2007

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

105

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“…Two-component systems provide a means for bacteria to sense nutritional and physical conditions, including temperature to adjust cell functions and virulence gene expression [159,160]. One prominent example of a thermosensing two-component system was identified in the plant-pathogenic bacterium Agrobacterium tumefaciens.…”

Section: Thermosensing Through Phosphorylation Of Sensor Kinasesmentioning

confidence: 99%

Thermosensing to Adjust Bacterial Virulence in a Fluctuating Environment

Steinmann

Dersch

2012

Future Microbiol.

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“…One simple yet highly sophisticated mechanism that bacteria utilise to effectively regulate the expression of virulence factors employs TCS 15,16 . TCS consist of two proteins; a histidine kinase which…”

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confidence: 99%

A key regulatory mechanism of antimicrobial resistance in pathogenic Acinetobacter baumannii

Adams¹

2017

Microbiol. Aust.

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Acinetobacter baumannii is a Gram-negative bacterial pathogen that has become a pressing global health issue in recent decades. Although virulence factors for this pathogen have been identified, details of how they are regulated are largely unknown. One widely employed regulatory mechanism that bacteria, such as A. baumannii, have adopted is through two component signal transduction systems (TCS). TCS consist of two proteins; a histidine kinase and response regulator. The histidine kinase allows the bacterium to sense alterations in the extracellular milieu, transmitting the information to the response regulator which prompts the cell to modify gene expression levels accordingly. Bacteria can encode multiple TCS, where each system can mediate specific responses to particular conditions or stressors. Identifying those conditions in which these TCS are expressed, and the genes they regulate known as their ‘regulon', is vital for understanding how A. baumannii survives and persists within the hospital environment or the human host during infection. As we enter the post-antibiotic era, knowledge of TCS could prove to be invaluable, as they offer an alternative target for the treatment of multidrug resistant bacterial infections.

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Two-Component Signal Transduction Systems, Environmental Signals, and Virulence

Cited by 67 publications

References 87 publications

Bacterial sensor kinase TodS interacts with agonistic and antagonistic signals

Bacterial sensor kinase TodS interacts with agonistic and antagonistic signals

Thermosensing to Adjust Bacterial Virulence in a Fluctuating Environment

A key regulatory mechanism of antimicrobial resistance in pathogenic Acinetobacter baumannii

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