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Mycobacterium tuberculosis
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
By studying the biology of the auxotrophic mutants of M. tuberculosis, it is clear that the tubercle bacillus, unlike many other intracellular pathogens, has evolved to have an autarkic or self-sufficient lifestyle. Other intracellular pathogens, such as Francisella or Legionella, are naturally occurring amino acid auxotrophs. Whereas, M. tuberculosis and M. leprae sequences reveal intact genes to synthesize all 20 amino acids,22,24M. tuberculosis fails to be able to multiply in mice if it is unable to make leucine,10 methionine,61 or arginine.62 Plants, fungi, and most bacteria have the ability to make all 20 amino acids. Legionella cannot make arginine, methionine, cysteine, leucine, valine, isoleucine, phenylalanine, and tyrosine. Interestingly, leucine starvation for M. tuberculosis is bacteriostatic whereas starvation for methionine or arginine is rapidly bactericidal thereby suggesting the enzymes to make these amino acids might be excellent drug targets.
Orotic aciduria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Orotic aciduria represents pyrimidine nucleotide starvation in man. It appears to be the first human nutritional auxotrophic disease to be recognized. The therapeutic effect of uridine is supportive of this hypothesis.
Consideration of Glutamine Synthetase as a Multifunctional Protein
Published in James F. Kane, Multifunctional Proteins: Catalytic/Structural and Regulatory, 2019
The first glutamine auxotroph reported had a mutation that was not within the glutamine synthetase structural gene of K. aerogenes.39 The reversion of this strain to glutamine prototrophy yielded mutants with mutations near or within glnA that caused elevated expression of glutamine synthetase. These results implied that the original mutations causing auxotrophy were in a gene whose product was necessary for the production of glutamine synthetase. This gene was designated glnB and reported to encode a regulatory protein for glutamine synthetase.39 Later, the glnB product was identified as being the PII protein, which determines whether the adenyl transferase adenylylates or deadenylylates glutamine synthetase, and its involvement in regulation was thought to function indirectly through the adenylylated glutamine synthetase.51 Since recent reports suggest that the elimination of the PII protein product leads to elevated synthesis of glutamine synthetase, the mechanism by which the glnB product participates in influencing glutamine synthetase production is not clear.52,53
Insight into the current Toxoplasma gondii DNA vaccine: a review article
Published in Expert Review of Vaccines, 2023
Xirui Zhang, Hao Yuan, Yasser S. Mahmmod, Zipeng Yang, Mengpo Zhao, Yining Song, Shengjun Luo, Xiu-Xiang Zhang, Zi-Guo Yuan
T. gondii is a protozoan parasite with a wide range of hosts. So far, researchers have tried different types of Toxoplasma vaccines, including recombinant vaccines, DNA vaccines, subunit vaccines, live attenuated vaccines, and nanoparticle vaccines [178,179]. Of these, only the live attenuated vaccine can offer desirable and effective protection against T. gondii [180]. However, existing attenuated vaccines have the disadvantages of being expensive, causing side effects and short shelf-life [11]. To overcome these shortcomings, researchers have turned their attention to the live attenuated mutants, among which the nutrient auxotrophic mutant was considered to be the most promising [12]. But due to the adverse effects it might cause and its risk of reverting back to a pathogenic strain, it is still destined not an ideal vaccine to be used in humans [10].
High throughput genome scale modeling predicts microbial vitamin requirements contribute to gut microbiome community structure
Published in Gut Microbes, 2022
Juan P. Molina Ortiz, Mark Norman Read, Dale David McClure, Andrew Holmes, Fariba Dehghani, Erin Rose Shanahan
Metabolite-driven interactions in bacterial communities have been extensively documented and reviewed.15–17 Yet, microbial coenzymes constitute an underexplored aspect of the gut environment that has recently been gaining momentum, particularly those also categorized as human vitamins.18–22 Vitamins have well-characterized biosynthetic and acquisition pathways,21 and constitute essential20,22 and optional nutrients23,24 for gut commensals. Previous observations report vitamin-restricted diet/media had nearly no impact in a community of gut auxotrophic species relative abundance.25 Recent evidence suggest that colon-targeted vitamin supplementation can alter microbial alpha diversity.26 Further, vitamin auxotrophy has been identified as a driver of co-dependence and cooperation in a synthetic microbial community.12 Similar dynamics have been proposed around bacterial quinones, which encompass menaquinones (vitamin K2) and ubiquinones.27,28 Together, these characteristics strongly suggest that cofactor-driven microbial interactions are intrinsic to higher order units in the gut microbiome.
Isolation and cultivation of candidate phyla radiation Saccharibacteria (TM7) bacteria in coculture with bacterial hosts
Published in Journal of Oral Microbiology, 2020
Pallavi P. Murugkar, Andrew J. Collins, Tsute Chen, Floyd E. Dewhirst
A third misconception about Saccharibacteria that may apply to other uncultured bacteria, including other CPR phyla, is that the uncultured status corresponds with fastidiousness and fragility. For example, many Treponema spp. are fastidious oxygen-sensitive obligate anaerobes that are fragile to mechanical manipulation. The Saccharibacteria we have isolated, in contrast, can be grown aerobically, microaerophilically or anaerobically depending only on their host’s oxic range and survive filtration and ultracentrifugation. Culture of Saccharibacteria required the presence of a host bacteria, not addition of novel factors to standard microbial media. Rather than varying media and conditions to achieve growth, binary or ternary bacterial coculture may fulfill all auxotrophic needs of some difficult to culture organisms.