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Loss of function of metabolic traits in typhoidal Salmonella without apparent genome degradation.
- Source :
-
MBio [mBio] 2024 May 08; Vol. 15 (5), pp. e0060724. Date of Electronic Publication: 2024 Apr 04. - Publication Year :
- 2024
-
Abstract
- 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.<br />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.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Humans
Genome, Bacterial
Salmonella paratyphi A genetics
Salmonella paratyphi A metabolism
Loss of Function Mutation
Bacterial Proteins genetics
Bacterial Proteins metabolism
Typhoid Fever microbiology
Serogroup
Metabolic Networks and Pathways genetics
Salmonella typhi genetics
Salmonella typhi metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2150-7511
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- MBio
- Publication Type :
- Academic Journal
- Accession number :
- 38572992
- Full Text :
- https://doi.org/10.1128/mbio.00607-24