Amino acid synthesis pathway in bacteria -
Therefore, the mere presence of amino acids in an extraterrestrial sample does not indicate a signature of life and cannot be used as a biomarker itself Parnell et al. Nevertheless, the abundance of certain amino acids in a sample might provide clues on the presence of microorganisms. While abiotic processing of amino acids is driven by thermodynamic processes, in biological systems their relative abundance is the result of metabolic activity in any given organism or a community Davila and McKay, In addition, life uses only a selection of amino acids, while extraterrestrial carbonaceous matter contains, as noted above, a much broader variety.
One method to investigate the presence of life, distinct from looking for the amino acids in life itself e. In many extraterrestrial environments, including Mars, we would expect amino acids in addition to other organic compounds to be available to any putative biota.
They are delivered to a planetary surface in carbonaceous chondrite meteorites Cronin and Pizzarello ; Ehrenfreund et al. For example, a wide range of amino acids has been detected in carbonaceous chondrites.
The frequency of the prebiotic synthesis of amino acids and their abundances follow thermodynamic principles with the chemically simple compounds being most abundant Miller, ; Pizzarello, ; Pizzarello and Shock, ; Glavin et al.
A large number of microorganisms can use amino acids as electron donors for anaerobic respiration or in fermentation Nixon et al. In this process, they degrade the amino acid molecules. Microorganisms are unlikely to degrade amino acids at the same rate compared to degradation by abiotic processes.
Rather, they will degrade the molecules according to their metabolic pathways, the accessibility of certain amino acids, the availability of other metabolizable organic compounds, and other organism-specific effects.
Thus, we could hypothesize that, in the process of degrading abiotic amino acids, microorganisms would leave a biosignature by the preferential degradation of certain amino acids in the environment around them. This biosignature might be superimposed on the biosignature of the amino acids in the organism itself and that were synthesized by the organism, but it would be a distinct and additional biosignature reflecting non-random biological destruction of the abiotic amino acid pool.
One attraction of such a biosignature is that, if cells alter the amino acid concentration in the environment around them, then, particularly in low biomass environments, that signature might be much more pervasive and easier to detect than the amino acid signature of the cells themselves, which could be highly localized and poorly preserved.
Furthermore, although this signature would assume the presence of amino acid-using life, the decrease or increase in any amino acids away from the expected background abiotic concentration could be an agnostic signature of metabolic processes.
In this study, we tested this hypothesis by investigating the metabolic usage of seven amino acids previously detected in both terrestrial environments and Martian meteorites by two distinct anaerobic microbial communities from Martian analog environments.
We used two distinct communities to determine if there were common patterns of degradation of certain amino acids that could potentially suggest a universal signature of amino acid degradation by life.
The almost complete degradation of glycine was common to both communities. For other amino acids, we observed different patterns of degradation with increased extracellular concentrations of some amino acids.
We discuss the implications of these findings for life detection. The samples investigated were collected in the frame of the MASE Mars Analogs for Space Exploration project, a 4-year collaborative research project supported by the European Commission Seventh Framework Contract.
The aim of the project was to characterize Mars analogue environments on Earth with regard to habitability and the search for potential biosignatures of extraterrestrial environments Cockell et al. Samples analyzed herein were collected from two sulfidic springs close to Regensburg, Germany, where many sulfide-containing springs emanate from Mesozoic karst formations.
The two springs, in the Sippenauer Moor SM and Islinger Mühlbach ISM areas The sites SM and ISM are independent and not connected in the deep subsurface. Detailed analyses of the site microbiomes are already available Moissl et al. All samples were taken under anoxic conditions for a detailed description see Cockell et al.
Cultivation was performed under anoxic conditions. Samples from SM and ISM were inoculated in anoxic MASE medium II and supplemented with a mixture of proteogenic and non-proteogenic amino acids.
MASE II medium contains per liter: NH 4 Cl 0. Prior to inoculation, the medium was supplemented with a filter-sterilized amino acid broth. Amino acids such as alanine, aspartic acid, glutamic acid, glycine, leucine, serine, and valine are common in both biological samples and for example, carbonaceous chondrite meteorite Cronin and Pizzarello, ; Shimoyama et al.
Based on these data, the following mixture of amino acids was added to the medium: glycine, L-alanine, β-alanine, L-aspartic acid, DL-proline, L-leucine, L-valine, L-phenylalanine and L-isoleucine Table 1. The amino acid broth used in this study included some proteinogenic amino acids that are most likely not found in meteorites due to their complexity in synthesis.
The final concentration of each added amino acid was 10 mM, and the pH was adjusted to 7. One millilitre of the environmental sample was added to 20 ml of medium and incubated at 30°C. A negative control NC , i. TABLE 1. Chemical properties of the supplemented amino acids and their side chains.
After defined time points, 1. The first sample was taken immediately after inoculation T0 , followed by samples after 7, 14, 28, 56, and 90 days of incubation. The sample was sterilized using a 0. Amino acid extraction was performed using a simplified procedure described in Aerts et al.
Therefore, the extraction protocol is described in the following only briefly. For sterilization, all glassware, including the columns with glass wool for amino acid extraction, were double wrapped in aluminum foil and placed into a furnace at °C for a minimum of 3 h. A sequential washing with basic-neutral-acid-basic solutions was made to activate the resin active sites.
After the sequential washing procedure, 1. The sample was vortexTed at 2, rpm for 30 s and subsequently added to the column. Note, that this first elution was not collected for further analysis and was disposed.
The system used for amino acid analysis is described in Aerts et al. Measurements were performed using an Agilent LC-MS system equipped with an ultraviolet UV and fluorescence FL detector system, an autosampler module where the amino acid derivatization is performed, and a MS ion trap mass spectrometer with electrospray ionisation.
The column used for analysis was a × 3 mm 2. The MS was operated in positive mode with optimised conditions for each individual amino acid. Amino acids were derivatised using a method based on Nimura and Kinoshita which was then automated in order to increase the robustness of the method.
This automation was achieved by programming the autosampler module Agilent GB of the HPLC to mix the various reagents. The approach used was as follows: the amino acid sample was mixed in a ratio with 0.
In a typical measurement run, amino acid samples from one time point including negative control were analysed sequentially, including wash procedures and the analysis of amino acid standard solutions Agilent, part number: — Proline was not measurable as it cannot be derivatized and is therefore not detectable using the applied method.
Standards were run at the beginning and end of each run in order to track reagent degradation and system performance. The standard deviation was added as error bars to the measurements of the amino acids of SM and ISM. FIGURE 1.
Degradation of glycine from the two different enrichments A Islinger Mühlbach ISM , and B Sippenauer Moor SM spiked with a broth of amino acids final concentration of each added amino acid was 10 mM over a time of 3 months.
C Negative control, i. FIGURE 2. LC-MS measurements of the three amino acids β-alanine, L-aspartic acid, and L-phenylalanine from the two different enrichments over a time of 3 months. A Islinger Mühlbach ISM , and B Sippenauer Moor SM spiked with a broth of amino acids final concentration of each added amino acids was 10 mM.
FIGURE 3. LC-MS measurements of the four amino acids L-alanine, L-valine, L-leucine, and L-isoleucine from the two different enrichments over a time of 3 months. A Islinger Mühlbach ISM , and B Sippenauer Moor SM spiked with a broth of amino acids final concentration of each added amino acid was 10 mM.
Using LC-MS measurements, we investigated the differences in the amino acid distribution in the medium of two different microbial enrichments and the negative control. We found that in the control samples in which no microbiota was added, no significant changes of amino acid concentrations were observed over time Figures 1 — 3.
Therefore, the changes observed in the inoculated samples are attributed to microbial activity. Note, because the signal of measured amino acids in NC for time point 56 days was significantly lower in comparison to the signal of the NC of the other time points, NC of time point 56 days was not considered for analysis.
No such decrease was observed for the measurements of amino acids in the SM and ISM samples of the same time point, which points to a sample problem and not to an instrument malfunction. The results after analysis using LC-MS revealed that the quantities of the non-glycine amino acids varied over time depending on the microbial community and the amino acid see Figures 1 — 3.
Although the concentrations of amino acids varied between the two enrichments, we found one amino acid characteristic that was consistent with both enrichments Figure 1.
The depletion follows an exponential decay; see fit to the date in panel B of Figure 1. Note, the same fit could not be applied to ISM1 data panel A because of missing sample for time point 7 days; the fit would be too steep at the beginning.
These data suggest a preferential use of glycine by these microbial communities. For all amino acids, we observed two different patterns of the measured relative ratios: 1 a differential use of amino acids was revealed, i. B-ala, L-asp, and L-phe did not reveal a clear trend with time Figure 2.
For example, in the ISM inoculum, the amount of β-ala and L-asp decreased over the first 2 weeks, followed by a peak 2.
In the SM inoculum, L-asp increased over the first three measurements before a steady, but small decrease was observed. In contrast, for β-ala the initial decrease was prolonged, before a peak followed by a decrease Figure 2B.
L-phe followed a similar trend in the SM sample Figure 2B , but it was less prevalent in the ISM sample Figure 2A. However, these trends were not significant. The measured amount of amino acids L-ala, L-val, L-leu, and L-ile in the media increased in IM enrichment compared to the observed decrease in the SM enrichment.
All four amino acids in the IM enrichment followed a similar pattern: Within the first 3 weeks an increase was detected followed by a plateau phase Figure 3A. The largest increase was seen for L-ala whereas only a small increase was detected for L-val. While in the SM sample, L-ile decreased the most and L-ala and L-leu were less depleted from the media, the plateau phase also started after about 2 weeks, revealing relatively small changes of the amino acid abundance Figure 3B.
This study investigated whether the fingerprints of microbial amino acid metabolism could be used as a potential biosignature. Beside a preferential use of amino acids, the microbial community can release certain amino acids as metabolic products into their surroundings.
The release can occur by excretion or passive diffusion or the result of cell death followed by cell lysis. In addition, a variety of abiotic processes leading to the formation or degradation of certain amino acids can result in a change of prevalent amino acid abundance within an environment.
The following discussion is based on the assumption that potential extraterrestrial life uses similar biochemistry in liquid water environments as observed for Earth-based life.
Life as we know it is based on mainly CHNOPS elements and other mineral sources for generating energy and the usage of amino acids to form proteins. The data obtained for glycine suggest a preferential use of glycine by microbial communities.
We found that almost all the glycine was depleted and we observed this for both communities, suggesting the possibility that glycine depletion in an environment would be consistent with life. There are several mechanisms in bacteria involved in glycine uptake and metabolism Sagers and Gunsalus, ; Andreesen, In anoxic environments, glycine can be a substrate in the Stickland reaction, which is a coupled oxidation-reduction reaction mainly for amino acid pairs Andreesen, Glycine serves preferentially as an electron acceptor which can be coupled to an energy conservation step.
Glycine and alanine can act as a redox couple in which glycine is reduced while alanine is oxidized. This reaction would also lead to a decrease in alanine, which is observed for the Sippenauer Moor SM sample Figure 2B but not for the Islinger Mühlbach ISM sample Figure 2A.
Consequently, these results could either indicate the presence of different metabolic activities in these communities or that the Stickland reaction is not the main mechanism leading to the reduction of glycine in the medium.
Another explanation for the microbial removal of glycine from the medium could be the result of an energy-producing reaction where two molecules of glycine could be used to form serine and CO 2.
This has previously been reported for Pediococcus glycinophilus Sagers and Gunsalus, Furthermore, glycine can be used as part of the peptidoglycan in the cell wall Veuger et al.
With the current experimental set-up, a detailed analysis on the metabolic mechanisms underlying the preferred removal of glycine is not possible.
However, the reduction of glycine and therefore the lack of detectability among the presence of other amino acids can be further explored as a potential biosignature. In order to evaluate whether the absence of glycine is a valuable biosignature to find life on Mars, its abiotic stability on Mars needs to be considered.
Glycine is one of the most abundant amino acids detected in meteorites and comets Botta and Bada, ; Elsila et al. Various laboratory studies have investigated not only the abiotic degradation of glycine Schuerger et al. Mars simulation studies determining the effect of UV irradiation on glycine revealed a degradation which results in the release of methane into the atmosphere Schuerger et al.
Owing to its simple chemical structure, glycine has the fastest degradation rate of amino acids. Extrapolated from ISS experiments, Noblet et al. Another set of exposure experiments on the ISS days for a total of 2, h solar constant radiation, equivalent to 1, Compared to UV radiation, galactic cosmic rays and solar energetic particles mainly protons can penetrate deeper into soil and ice Mancinelli and Klovstad, A decrease by a factor 5—10 in a depth of a few meters is expected from the surface dose rate of 0.
Gerakines and Hudson performed experiments to study the half-lives of glycine in either CO 2 -ice or H 2 O-ice when irradiated with protons. The destruction rate constants indicated that glycine is less stable in CO 2 -ice Mars compared to H 2 O-ice Mars and Europa.
When extrapolating these data to conditions in the Martian subsurface, the half-life of glycine is modelled to be less than — million years even at depths of a few meters Gerakines and Hudson, Other studies estimated that amino acids when shielded from radiation could potentially survive billions of years in cold and dry niches on Mars Ehrenfreund and Charnley, ; Ehrenfreund et al.
Similar conclusions apply to Europa, Pluto, other icy satellites and to comets Gerakines and Hudson, Furthermore, a temperature effect has been observed in a previous study Gerakines et al.
With increasing temperatures, amino acids are less stable Gerakines et al. In addition, the mineralogy of the Martian regolith has an influence on the preservation of amino acids. Clay minerals or sulfate rich environments have been reported to show higher preservation rates compared to minerals containing ferrous iron dos Santos et al.
This effect was also noted in space exposure experiments where amino acids intermixed with meteorite powder had a higher stability than without Bertrand et al. These data imply that, in order to determine a biotic origin for the absence of glycine, several factors have to be considered.
Due to the thermodynamics and kinetics of amino acid synthesis this observation is remarkably consistent for any synthesis environment.
And lastly, the prevalence of glycine in an environment on Mars will be the result of a combination of these factors. In conclusion, the biotic degradation of glycine has potential as a biosignature of metabolic activity, but to avoid a false positive, it is necessary to understand the environmental conditions and context of the samples and the abiotic pathways and kinetics of glycine degradation.
Contrary to the glycine observations, there was no similar trend for the other amino acids in both samples. These complex and different changes in both enrichments could be the result of: 1 different chemical properties Table 1 , 2 the interaction of the various biochemical roles of amino acids, and 3 the composition of the microbial community.
Amino acids are not only the building blocks of proteins, but have other functions including the use as energy metabolites, essential nutrients, or chemical messengers in communication between cells. Therefore, changes in the detectable amount of amino acids may represent the integrated effect of a diversity of metabolic pathways occurring in the respective microbial communities.
Microbial amino acid metabolism is a complex system involving transporters for uptake, biosynthesis as well as degradation and extraction of amino acids in a single microorganism.
Transport mechanisms and metabolic pathways for the individual amino acids vary considerably in complexity Krämer, There are two mechanisms that could lead to different fingerprints.
On the one hand, as is the case in our experimental set-up, when amino acids are available in the environment, they are transported into the cells using different uptake systems. Differential consumption and utilization rates of the available substrate lead to a decrease of a certain amino acid.
On the other hand, amino acids can be excreted from the cells. The formation of amino acids and intermediates in the course of amino acid metabolism which are released into the environment results in an increase of a certain amino acid. In addition, the complexity increases when investigating microbial communities as amino acid production and utilization are characterized by the sequential action of different metabolic pathways in organisms belonging to a consortium.
There is the potential that an amino acid released into the medium from one member of the community can be utilized by another member and is therefore not detectable in the medium. The results from the ISM enrichment revealed a higher amount of L-ala, L-val, L-leu and L-ile after incubation than initially added to the medium.
This could be the result of amino acid synthesis from precursor molecules which then have been released into the medium either via active transport, diffusion or is a result of cell death and subsequent lysis Gutiérrez-Preciado et al.
Furthermore, the external increase of alanine might be indicative of a passive efflux which also has been observed for proline, aromatic and branched chain amino acids Driessen, ; Krämer, These results show how, in addition to the potential biosignature of the cells themselves, microbial metabolisms might increase the surrounding environmental concentrations of amino acids above those expected abiotically, suggesting that anomalously high concentrations of amino acids could be a biosignature.
If these amino acids leached into preserved sediments where there was no preservation of cells themselves, they might act as an indirect signature of the proximal presence of life. Although we observed high concentrations of alanine, in principle an increase in any amino acid anomalously above the expected abiotic background could be an agnostic signature of biological processes.
We observed a decrease in the abundance of amino acids in the surrounding environment in the SM enrichment. One explanation for higher rates of substrate metabolism compared to biosynthesis leading to a reduction of amino acids, might be that the microbial community was performing maintenance metabolism rather than active growth.
As with glycine, in order to be useful as a biosignature, these observed decreases would have to be considered alongside abiotic degradation rates. As for glycine, the UV photodestruction rate for L-alanine and β-alanine is dependent on whether the amino acids are on the surface free or embedded in UV non-penetrable solid surfaces subsurface , or embedded in UV penetrable surfaces such as ice.
On Mars, the half-life of ala with a radiation dose rate of 2. Similar values with variations of about two orders of magnitude have been proposed for Pluto, comets in the outer Solar System, a cold diffuse and a dense interstellar medium Gerakines and Hudson, As seen for glycine, the half-lives are several orders of magnitude lower for Europa at the near surface 1, years at 1 cm.
In summary, these data suggest that the individual fingerprints of the amino acids alanine, aspartic acid, valine, leucine, isoleucine and phenylalanine can vary, i. Cultivation and subsequent isolation has shown that the microbial communities from these two samples vary significantly Cockell et al.
Although these complexities do not rule out such amino acid degradation patterns as biosignatures, they suggest that further investigation would be needed on any given sample, including its geological and temporal context, to determine if the differential changes in the amino acids in different communities can be disentangled from the expected abiotic degradation processes and attributed to a potential metabolic influence.
Nevertheless, the observed synthesis and extracellular excretion of amino acids, leading to a large local increase in the concentration of some amino acids, as observed in the ISM sample, might be another promising signature of life. The results of this study demonstrate a new type of amino acid imprint in an environment as a biomarker, which could be used alongside other methods to identify past and present life in extraterrestrial environments.
The results indicate that the biologically mediated and almost complete depletion of glycine could be one amino acid signature that could be sought to corroborate the presence of life.
Other amino acids showed diverse changes. Depletions could only be a biosignature if, like glycine, they can be disentangled from abiotic changes, but their presence would at least be consistent with life.
Perhaps more interestingly, large increases in concentrations of amino acids resulting from excretion, might also be an agnostic indication of the presence of microbiota metabolizing amino acids.
The results we present here show how the effects of life on the surrounding amino acid profile may be another organic signature of its presence and metabolic activities.
The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author. PS contributed to the experimental protocol, performed the experiments, data analysis, and wrote the manuscript. AR and DM performed the LC-MS measurements; PH, RL assisted in performing experiments and contributed by proof reading the manuscript.
CS conceptualized the project as a whole and helped write the manuscript. All authors engaged in discussions, proof-read and approved the final manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Aerts, J. Biota and Biomolecules in Extreme Environments on Earth: Implications for Life Detection on Mars.
Life 4, — PubMed Abstract CrossRef Full Text Google Scholar. A Contamination Assessment of the CI Carbonaceous Meteorite Orgueil Using a DNA-Directed Approach. CrossRef Full Text Google Scholar. Biosignature Analysis of Mars Soil Analogs from the Atacama Desert: Challenges and Implications for Future Missions to Mars.
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Bashir, A. Taxonomic and Functional Analyses of Intact Microbial Communities Thriving in Extreme, Astrobiology-Relevant, Anoxic Sites. Microbiome 9, Bertrand, M. The AMINO experiment: Exposure of Amino Acids in the EXPOSE-R experiment on the International Space Station and in Laboratory.
Botta, O. A similar situation exists during infection by Salmonella typhimurium , where the effect on serine synthesis is mediated by the bacterial protein SopE2 a type III secretion system effector encoded in the pathogenicity island SPI Following infection of macrophages by S. typhimurium , metabolomic data suggested an enhanced glycolysis and reduced serine synthesis in the infected macrophages Jiang et al..
Glycine is a key non-essential amino acid for both leukocyte proliferation and antioxidant defense Li et al.. Infection of rabbit bronchial cells by B. septicum caused the activation of the glycine pathway, leading to an increase in intracellular glycine level Xiao et al..
However, such elevation was not seen in every microorganism infected cells. For example, a marked reduction of glycine was reported in H. pylori and Vibrio parahaemolyticus infected cells Nguyen et al.. This occurs frequently in the nature world. ETEC infection lowered the concentration of isoleucine and non-essential amino acids, such as glutamine, asparagine, citrulline, and ornithine in piglet serum, while increased the levels of glycine and aminobutyric acid.
The underlying mechanism of this effector has been described in two ways: one suggests that it changes the rate of amino acid transport, while the other revealed a declined synthesis of non-essential amino acids due to the lack of carbon donor precursors. In addition to influencing amino acid metabolism, the effector VopQ can modify the host immune system by stimulating autophagy in both phagocytic and non-phagocytic cells Higa et al..
Histidine, an alkaline amino acid, is mostly synthesized through decarboxylase by histidine deaminase, and considered to be an essential amino acid in human. This amino acid can be utilized as a nutrient for supporting bacterial survival, as it has been revealed by Daniela et al..
that histidine level in organoids derived from the stomach antrum and corpus was decreased after H. pylori infection Keilberg, et al.. The reduction of histidine may also be triggered by bacteria-related metabolic reprogram, leading to the modified host metabolism and the activation of autophagy response.
Take S. aureus as an example, l -Phenylalanine can be synthesized by MRSA from 3-phenylpyruvic acid and histidine through histidine-phosphate transaminase Bravo-Santano et al..
The host cell's histidine is consumed not just as an energy source for the bacteria, but also as a donor for l -Phenylalanine. Likewise, B.
abortus -mediated perturbation of host mitochondrial function prohibits the entry of any amino acid, including histidine, into the TCA cycle Czyz et al.. Histidine in the gut microbiota also produces a variety of metabolite molecules that affect the host, such as imidazole propionic acid IMP , which is elevated in T2MD and impairs insulin signaling by activating the p38 γ-p62—mTORC1 pathway.
l -Cysteine is a common sulfur-containing amino acid in mammals. The most important function of l -Cysteine is to scavenge free radicals, antioxidants, and copper integrators. Microorganisms can gain energy from the carbon chain of l -Cysteine through desulphurases, such as methionine that can be converted into α-keto-butyrate, ammonia and methanethiol.
The underlying mechanism of bacteria-imposed host cell damage may be due to the rapid ingestion of large amounts of thiocysteine CySS, then converting them into cysteine Cys.
Fenton reaction driven by endogenous cysteine in E. coli may promote drug resistance. Moreover, to improve legionella growth and reproduction, SLC1A5 neutral amino acid specific , an amino acid transporter, was highly induced to express on LCV membrane, and promote the absorption and transport of serine, l -Glutamine or cysteine Eisenreich and Heuner Methionine is a sulfur-containing essential amino acid, which is closely related to the metabolism of various sulfur-containing compounds in the organism.
Methionine is the most abundant sulfur-containing amino acid, and is the main supplier of sulfur for the host.
Methionine is able to convert into l -Cysteine and glutathione, which acts as an antioxidant and antidote in the body, helping to ward off cell damage caused by the highly oxidative environment created by bacteria.
Pathogen infection usually caused an accumulation of methionine in living cells, which has cytoprotective and antioxidant functions Bender et al.. For example, V. parahaemolyticus -infected male and female abalone both showed elevated methionine levels Lu et al..
Methionine is essential for maintaining the normal level of folate in host and bacteria. For example, metformin-induced damage to the methionine cycle in E. coli leads to the increased synthesis of SAMe, thus, restricting methionine production by blocking methylene THF reductase, inhibiting the E.
coli folate cycle and extending host life Induri et al.. Proline as an non-essential amino acid is a fundamental substrate for almost all proteins. The main function of this amino acid is to help the body to decompose proteins.
Meanwhile, it is an critical component of collagen. Proline is involved in metabolism as a nutrient. Microorganisms such as E. coli, Gram-negative S. enterica , and Klebsiella spp.
can utilize it as a sole nitrogen or carbon source, leading to a decrease in the host proline level Moses et al.. Moreover, as revealed by Faiza et al..
Proline is also indispensable for bacteria to defense against temperature and oxidation. Lagautriere et al.. identified the proline metabolic pathway is necessary for the persistence of M. tuberculosis in the host Lagautriere et al..
Pathogen-related metabolic reprogram usually causes a decrease in proline level. For example, microorganism such as B. abortus infection results in the disruption of host mitochondrial function, thereby affecting the host amino acid metabolism.
The infected cells are unable to metabolize any amino acids entering the TCA cycle, but interestingly, host glucose metabolism is not affected Czyz et al.. Reduction of total amino acid content due to the decreased host amino acid transport during P.
aeruginosa infection, including proline, may be mediated by the addition of γ-glutamyl groups to γ-glutamyltransferases Mahmud et al.. As an aromatic amino acid in human body, most of l -Phenylalanine is oxidized to tyrosine by PAH catalysis, producing l -Phenylalanine or tyrosine-derived dopamine in the gut, which plays an important role in controlling movement and mood.
A significant increase in the ratio of l -Phenylalanine to tyrosine could be an indicator of the inflammatory activity. MRSA can synthesize l -Phenylalanine from 3-phenylpyruvic acid and histidine, resulting in differences in host histidine and l -Phenylalanine levels.
In Klebsiella pneumoniae -infected hosts, enrichment pathway analysis revealed the activation of host metabolism of arginine, l -aspartic acid, and l -Phenylalanine. Human macrophage-like cells infected with B. abortus showed decreased TCA cycle metabolism and reduced amino acid consumption as well as the hindered capability of host cells to utilize amino acids.
Likewise, an increased abundance of phenylalanine, leucine, l -Isoleucine and threonine was detected due to S. pneumoniae infection, whereas the underlying mechanism still remains unknown. l -Phenylalanine and tyrosine could also be used as energy sources by pathogens.
The levels of l -Phenylalanine, tryptophan and tyrosine in the liver and pancreas of female abalone infected with Vibrio decreased significantly. Similar phenomenon also observed in H. pylori -infected gastric corpus organoids. Within our review, we undertake a comprehensive examination of alterations occurring in the host's amino acid profile subsequent to pathogenic invasion—an area of substantial significance within the domain of pathogen—host interplay investigation.
Through meticulous scrutiny of an array of illustrative case studies, we endeavor not only to unveil the intricate panorama of these modifications, but also to glean profound insights into their pivotal involvement in orchestrating the immune retort and intricacies of infection-associated metabolism.
Evident from our meticulous review is the unequivocal capacity of bacterial incursion to intricately perturb the host's amino acid metabolism, orchestrating this modulation through a panoply of mechanisms—ranging from amino acid uptake, synthesis, transport, utilization, to hydrolysis.
This overarching influence extends far and wide, encapsulating the precise targeting of genes encoding pertinent amino acids, the recalibration of central carbon metabolism, the dynamic activation or restraint of autophagic processes, and the nuanced modulation of amino acid synthesis, transporters, enzymatic kinetics, and sensory apparatuses.
The landscape thus unfurled was marked by discernible differentiations in the patterns of amino acid alterations, exhibiting distinct signatures tailored to diverse pathogenic agents and host entities. These cascading perturbations find their resonance in the intricate web of host cell metabolic pathways, profoundly steering their energy provisioning dynamics and immune responsiveness Fig.
This symphony of alterations holds within its grasp the potential to precipitate a plethora of pivotal outcomes within the realm of infection, encapsulating a spectrum of arenas including but not limited to the following five aspects.
AA starvation: amino acid starvation; AMD: membrane damage; ARG: arginine hydrolase; Arg: arginine; Asn: asparagine; Asp: asparagine; DC: dendritic cells; Gln: glutamine; LCV: Legionella-containing vesicles; Leu: leucine; L.
pneumophila : Legionella pneumophila ; MRSA: methicillin-resistant Staphylococcus aureus ; S. aureus : Staphylococcus aureus ; S.
typhimurium : Salmonella typhimurium; SLC: solute carrier; TB: Mycobacterium tuberculosis ; TCA Cycle: tricarboxylic acid cycle; Ile: isoleucine; VP: Vibrio parahaemolyticus. The first aspect centers on the orchestration of the immune response: nuanced shifts in specific amino acids hold the potential to intricately modulate the regulatory framework governing the host's immune machinery.
These select alterations within amino acid profiles have the potential to serve as catalysts, potentially setting in motion a cascade of events culminating in the activation of immune cells and consequent amplification of the inflammatory cascade. This intricate phenomenon is intricately orchestrated by manifold mechanisms, encompassing the potentiation of immune cell activation, the induction of cytokine release, and the judicious orchestration of T cell responsiveness.
Significantly, l -Glutamine , heralded for its pivotal role as an energetic substrate within immune cells, emerges as a pivotal factor dictating cellular proliferation kinetics and activation status. The delicate perturbations in l -Glutamine provisioning unveil its potential to profoundly influence immune cell functionality and the finely tuned equilibrium of immune responsiveness Newsholme et al..
Similarly noteworthy, Arginine, positioned as a linchpin within this narrative, assumes multifaceted roles. Certain pathogens adroitly leverage Arginine and the machinery of arginine synthetase to circumvent the host cell's immune response and signaling machinery Bronte and Zanovello Cysteine, a sulfur-containing amino acid, participates in the synthesis of glutathione within cells, thereby influencing the cellular redox state.
Variations in cysteine supply can potentially impact the antioxidant capacity and immune activity of immune cells Droge and Breitkreutz The subsequent dimension entails host metabolic reconfiguration: select amino acid shifts wield the potential to intricately navigate the labyrinthine network of host metabolic pathways.
This engenders a potential for the orchestrated rerouting of metabolic trajectories, instating an environment more conducive to pathogenic proliferation. Concurrently, these metabolic recalibrations may impose a transformative influence upon the host cell's energy provisioning and nutrient requisites—strategically accommodating pathogen survival and replication.
To illustrate, l -Glutamine , a cardinal participant in normative metabolic orchestration, emerges as a prominent protagonist within the realm of infectious diseases. The escalated requisites inherent to immune cells and other swiftly multiplying entities drive an amplified demand for l -Glutamine , a requirement to satiate their escalated energy and nitrogen essentials.
This dynamic engenders augmented l -Glutamine consumption, instigating a domino effect of metabolic modifications within the host milieu, calibrated to satiate the burgeoning exigencies of the immune response Curi et al.. Arginine, an intrinsic player in this narrative, finds itself enmeshed within the realms of infection.
Here, potential disruptions in Arginine metabolism reverberate into the precincts of the host's disease resistance. Within the contours of inflammatory milieus, Arginine's roles diversify to encompass the generation of reactive nitrogen species, thereby precipitating a scenario, wherein insufficient Arginine provisioning culminates in compromised immune cell activity Wu and Morris Similarly, Tryptophan, a cornerstone in serotonin and melatonin production, succumbs to perturbations within its metabolic stride during infection.
For instance, the action of Nitric oxide synthase can potentially engineer a recalibration within the Tryptophan metabolic pathway, leading to a depleted Tryptophan supply. This intricate cascade has the potential to exert cascading repercussions upon host immune regulation and cellular signaling Munn and Mellor In parallel, the saga unfolds for l -Cysteine, which might be coerced into a heightened requisition to combat oxidative stress.
This cascading demand may inadvertently trigger a diminution within l -Cysteine provisioning, ultimately underscoring its potential to modulate glutathione synthesis and, concomitantly, the delicate equilibrium encapsulated within the cellular redox landscape Droge Finally, within the complex interplay of inflammation and infection, Methionine's metabolic trajectory is not immune to transformation.
These shifts can transmute the trajectory of Methionine metabolism, ushering perturbations within its very fabric and inducing nuanced shifts in the production of select inflammatory mediators Jeckel et al.. Third, a pivotal aspect emerges in the form of the modulation of bacteria—host interactions, wherein host amino acid variations can profoundly influence the intricate interplay between pathogens and their host environment.
This encompasses a gamut of processes spanning attachment, invasion, and circumvention of host defense mechanisms orchestrated by pathogens. The ramifications are far-reaching: select amino acid modifications potentially engender transformations in the molecular landscape of host cell surfaces, thereby conferring potent influence upon the interplay with pathogens.
Arginine assumes a paramount role in this discourse—certain pathogens adeptly exploit arginine and the machinery of arginine synthetase to intricately subvert the host cell's immune retort and signaling conduits Hung et al.. Similarly, l -asparagine, by virtue of its strategic positioning, holds sway over the adhesive and invasive comportment of bacteria within the milieu of bacteria—host interplay.
Some pathogens astutely harness l -asparagine within host cells as a host-driven strategy for propagation Shah and Swiatlo Equally discernible, methionine surfaces as a modulator of import—some pathogens deftly utilize the host cell's methionine metabolism pathway to obfuscate the functional and signaling modalities of host cells, thus orchestrating a nuanced manipulation of the pathogen—host interplay Kipkorir et al..
Fourth, the interplay of inflammation and disease progression assumes prominence, as distinct amino acid perturbations may catalyze the escalation of immune-driven inflammation, thereby augmenting the vulnerability to tissue damage.
The protraction of this inflammatory milieu further precipitates the trajectory towards disease emergence, encompassing entities, such as chronic inflammation-related disorders. Arginine, its metabolites, such as nitrite and polyamines, emerge as pivotal players in immune inflammation orchestration.
Notably, certain investigations posit that undue arginine intake may potentiate immune inflammation, especially under specific chronic inflammatory contexts Wu and Morris ; Morris Similarly, Methionine, a sulfur-enriched amino acid, forges integral links within diverse biosynthetic cascades within immune cells.
In-depth examinations have illuminated a correlation between Methionine metabolism and the modulation of inflammatory response and immune cell activation, potentially influencing immune inflammation dynamics McGaha et al.. Lysine, an indispensable amino acid, entwines within multifarious cellular processes, including protein modifications and immune retorts.
An equilibrium disruption in lysine and other amino acid provisioning potentially assumes a role within select inflammatory ailments Smriga et al.. Fifth, a pivotal dimension emerges in the form of the influence exerted upon drugs and therapeutic strategies: host amino acid fluctuations bear the potential to recalibrate drug metabolism and mechanisms of action, consequently reverberating through the spectrum of infection management.
Variations within host amino acids can wield a potent influence over drug absorption, distribution, metabolism, and excretion, underscoring the necessity of a comprehensive comprehension of these dynamics to optimize drug selection and therapeutic regimens.
The spotlight falls on Lysine, whose metabolism and concentration might influence drug—protein binding. As certain pharmaceutical agents operate through protein binding, alterations in host lysine levels can potentially modulate drug—protein interactions Hacker et al..
In addition, leucine, a crucial branched-chain amino acid, might intricately participate in drug absorption and distribution, thereby potentially influencing the bioavailability and tissue dispersion dynamics Emami et al.. Within this gamut, l -Glutamine surfaces as an Essential amino acid, pivotal within diverse host biological processes.
Interactions between drug and l -Glutamine metabolism within the host milieu may potentially intertwine, ultimately influencing drug metabolism and therapeutic efficacy Slominski et al.. In summation, amino acids wield a pivotal role within the intricate mosaic of bacterial infection dynamics, encompassing realms of immune modulation, metabolic sustenance, protein synthesis, and an array of other biological facets.
The prospect emerges that the targeted modulation of amino acid metabolism for specific infectious entities holds the potential for innovative avenues in research, promising advancements in disease mitigation, treatment, or prophylaxis.
This modulation can potentially ameliorate disease symptoms, buttress immune functionality, and temper inflammation, collectively exerting a constructive impact.
Amino acids such as arginine, l -Glutamine , and l -Cysteine stand out as candidates with potential roles in immune regulation and inflammation attenuation. The meticulous regulation of these key amino acids' metabolism could potentially serve as an instrumental lever to intervene in infection progression and immune inflammation.
Furthermore, amino acid supplementation might serve to bolster cellular energetics and metabolic fortitude, thereby bolstering the host immune repertoire. However, salient considerations should be kept in view.
The intricacies at play in infection initiation and development typically stem from a nexus of factors, with amino acids merely comprising one facet of this complexity. Moreover, individual variability, encompassing divergent metabolic statuses and immune responses, underscores the necessity for personalized treatment approaches tailored to specific circumstances.
The validation in clinical settings is imperative, as while certain investigations have offered insights into amino acids' potential role in infectious diseases, a robust body of clinical evidence is requisite to substantiate their efficacy and safety.
Strategic therapeutic modalities that harness amino acids, whether as adjuncts, prophylactic strategies, or primary therapies, must be rigorously assessed in terms of their potential benefits, risks, and compatibility with conventional therapeutic paradigms.
We are compelled to explore the potential adjunctive application of amino acids alongside antibiotics. The intricate regulatory interplay of amino acids and their metabolites, within the backdrop of infection, encapsulates the transmission of signaling molecules within the infection microenvironment, the acquisition of proliferative prowess, and the elicitation of immune responses.
Consequently, future explorations must be oriented towards comprehending the core enzymes of amino acid metabolism, delineating the manifold signaling cascades emanating from amino acid metabolism, and understanding their intricate intersection with glucose and lipid metabolism.
This trajectory serves as a foundation for unveiling the intricate sensing mechanisms and feedback loops governing amino acid metabolism within the tapestry of infection progression, encompassing its expansive clinical applicability. Data availability is not applicable to this article as no new data were created or analyzed in this study.
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Amino acids are the structural units Amino acid synthesis pathway in bacteria aid up proteins. Amink join together to form short polymer chains called Antioxidant skincare products or longer chains called either polypeptides patyway proteins. These Amino acid synthesis pathway in bacteria acie linear and unbranched, with each amino acid within the chain attached to two neighboring amino acids. The process of making proteins is called translation and involves the step-by-step addition of amino acids to a growing protein chain by a ribozyme that is called a ribosome. Twenty-two amino acids are naturally incorporated into polypeptides and are called proteinogenic or natural amino acids. Of these, 20 are encoded by the universal genetic code. This page has been archived and is no longer updated. Amino acid synthesis pathway in bacteria acids play a central role in Chromium browser for media streaming metabolismand organisms synthesjs to synthesize most of Amino acid synthesis pathway in bacteria Figure patyway. Many of acud become familiar with amino acids patyway we first ih about translationthe synthesis of protein from the nucleic acid code in mRNA. To date, scientists have discovered more than five hundred amino acids in nature, but only twenty-two participate in translation. After this initial burst of discovery, two additional amino acids, which are not used by all organisms, were added to the list: selenocysteine Bock and pyrrolysine Srinivasan et al. Aside from their role in composing proteins, amino acids have many biologically important functions. They are also energy metabolites, and many of them are essential nutrients.
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