The family of organo-phosphate transport proteins includes a transmembrane regulatory protein

Kadner, Robert J.; Webber, Carol A.; Island, Michael D.

doi:10.1007/bf00770251

“…Paratyphi A is of potential physiological significance. The import of G6P is mediated by the UhpT antiporter, whose expression is strictly controlled by an unconventional two-component regulatory system composed of the membrane-localized UhpC sensor and UhpB kinase/phosphatase, and the cytoplasmic response regulator UhpA ( 23 , 24 ). In this system, UhpC directly senses G6P triggering a conformational change in the interacting kinase UhpB, which in turn phosphorylates and activates the response regulator UhpA.…”

Section: Resultsmentioning

confidence: 99%

Loss of function of metabolic traits in typhoidal Salmonella without apparent genome degradation

Machado,

Galán

2024

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Salmonella enterica serovar Typhi and Paratyphi A are the cause of typhoid and paratyphoid fever in humans, which are systemic life-threatening illnesses. Both serovars are exclusively adapted to the human host, where they can cause life-long persistent infection. A distinct feature of these serovars is the presence of a relatively high number of degraded coding sequences coding for metabolic pathways, most likely a consequence of their adaptation to a single host. As a result of convergent evolution, these serovars shared many of the degraded coding sequences although often affecting different genes in the same metabolic pathway. However, there are several coding sequences that appear intact in one serovar while clearly degraded in the other, suggesting differences in their metabolic capabilities. Here, we examined the functionality of metabolic pathways that appear intact in S . Typhi but that show clear signs of degradation in S . Paratyphi A. We found that, in all cases, the existence of single amino acid substitutions in S . Typhi metabolic enzymes, transporters, or transcription regulators resulted in the inactivation of these metabolic pathways. Thus, the inability of S . Typhi to metabolize Glucose-6-Phosphate or 3-phosphoglyceric acid is due to the silencing of the expression of the genes encoding the transporters for these compounds due to point mutations in the transcriptional regulatory proteins. In contrast, its inability to utilize glucarate or galactarate is due to the presence of point mutations in the transporter and enzymes necessary for the metabolism of these sugars. These studies provide additional support for the concept of adaptive convergent evolution of these two human-adapted S. enterica serovars and highlight a limitation of bioinformatic approaches to predict metabolic capabilities. IMPORTANCE Salmonella enterica serovar Typhi and Paratyphi A are the cause of typhoid and paratyphoid fever in humans, which are systemic life-threatening illnesses. Both serovars can only infect the human host, where they can cause life-long persistent infection. Because of their adaptation to the human host, these bacterial pathogens have changed their metabolism, leading to the loss of their ability to utilize certain nutrients. In this study we examined the functionality of metabolic pathways that appear intact in S . Typhi but that show clear signs of degradation in S . Paratyphi A. We found that, in all cases, the existence of single amino acid substitutions in S . Typhi metabolic enzymes, transporters, or transcription regulators resulted in the inactivation of these metabolic pathways. These studies provide additional support for the concept of adaptive convergent evolution of these two human-adapted S. enterica serovars.

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“…As some S. enterica serovars such as S. Typhimurium can gain access to the cytosolic environment (22), the observation of potential differences in the ability to utilize G6P by S. Typhi and S. Paratyphi A is of potential physiological significance. The import of G6P is mediated by the UhpT antiporter, whose expression is strictly controlled by an unconventional two-component regulatory system composed of the membrane-localized UhpC sensor and UhpB kinase/phosphatase, and the cytoplasmic response regulator UhpA (23,24). In this system, UhpC directly senses G6P triggering a conformational change in the interacting kinase UhpB, which in turn phosphorylates and activates the response regulator UhpA.…”

Section: Glucose-6-phophate (G6p) Sensing and Transcription Regulatio...mentioning

confidence: 99%

Loss of function of metabolic traits in typhoidalSalmonellawithout apparent genome degradation

Machado,

Galán

2024

Preprint

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Salmonella enterica serovar Typhi and Paratyphi A are the cause of typhoid and paratyphoid fever in humans, which are systemic life-threatening illnesses. Both serovars are exclusively adapted to the human host, where they can cause life-long persistent infection. A distinct feature of these serovars is the presence of a relatively high number of degraded coding sequences coding for metabolic pathways, most likely a consequence of their adaptation to a single host. As a result of convergent evolution, these serovars shared many of the degraded coding sequences although often affecting different genes in the same metabolic pathway. However, there are several coding sequences that appear intact in one serovar while clearly degraded in the other, suggesting differences in their metabolic capabilities. Here, we examined the functionality of metabolic pathways that appear intact in S. Typhi but that show clear signs of degradation in S. Paratyphi A. We found that, in all cases, the existence of single amino acid substitutions in S. Typhi metabolic enzymes, transporters, or transcription regulators resulted in the inactivation of these metabolic pathways. Thus, the inability of S. Typhi to metabolize Glucose-6-Phosphate or 3-phosphoglyceric acid is due to the silencing of the expression of the genes encoding the transporters for these compounds due to point mutations in the transcriptional regulatory proteins. In contrast, its inability to utilize glucarate or galactarate is due to the presence of point mutations in the transporter and enzymes necessary for the metabolism of these sugars. These studies provide additional support for the concept of adaptive convergent evolution of these two human-adapted Salmonella enterica serovars and highlight a limitation of bioinformatic approaches to predict metabolic capabilities.

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Glucose-6-phosphate transporter and receptor functions of the glucose 6-phosphatase system analyzed from a consensus defined by multiple alignments

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²

2000

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The family of organo-phosphate transport proteins includes a transmembrane regulatory protein

Cited by 19 publications

References 31 publications

Loss of function of metabolic traits in typhoidal Salmonella without apparent genome degradation

Loss of function of metabolic traits in typhoidal Salmonella without apparent genome degradation

Loss of function of metabolic traits in typhoidalSalmonellawithout apparent genome degradation

Glucose-6-phosphate transporter and receptor functions of the glucose 6-phosphatase system analyzed from a consensus defined by multiple alignments

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