Oligo-heterotrophic activity of Marinobacter subterrani creates an indirect Fe(II)-oxidation phenotype in gradient tubes

Autotrophic bacteria utilizing Fe(II) as their energy and electron sources for growth affect multiple biogeochemical cycles. Some chemoheterotrophic bacteria have also been considered to exhibit an Fe(II) oxidation phenotype. For example, several Marinobacter strains have been reported to oxidize Fe(II) based on formation of oxidized iron bands in semi-solid gradient tubes that produce opposing concentration gradients of Fe(II) and oxygen. While gradient tubes are a simple and visually compelling method to test for Fe(II) oxidation, this method alone cannot confirm if, and to what extent, Fe(II) oxidation is linked to metabolism in chemoheterotrophic bacteria. Here we probe the possibility of protein-mediated and metabolic byproduct-mediated Fe(II) oxidation in Marinobacter subterrani JG233, a chemoheterotroph previously proposed to oxidize Fe(II). Results from conditional and mutant studies, along with measurements of Fe(II) oxidation rates suggest M. subterrani is unlikely to facilitate Fe(II) oxidation under microaerobic conditions. We conclude that the Fe(II) oxidation phenotype observed in gradient tubes inoculated with M. subterrani JG233 is a result of oligo-heterotrophic activity, shifting the location where oxygen dependent chemical Fe(II) oxidation occurs, rather than a biologically-mediated process. Importance Gradient tubes are the most commonly used method to isolate and identify neutrophilic Fe(II)-oxidizing bacteria. The formation of oxidized iron bands in gradient tubes provides a compelling assay to ascribe the ability to oxidize Fe(II) to autotrophic bacteria whose growth is dependent on Fe(II) oxidation. However, the physiological significance of Fe(II) oxidation in chemoheterotrophic bacteria is less well understood. Our work suggests that oligo-heterotrophic activity of certain bacteria may create a false-positive phenotype in gradient tubes by altering the location of the abiotic, oxygen-mediated oxidized iron band. Based on the results and analysis presented here, we caution against utilizing gradient tubes as the sole evidence for the capability of a strain to oxidize Fe(II) and that additional experiments are necessary to ascribe this phenotype to new isolates.

Artificial Aggrecan prodrugs in the treatment of Arthrosis

Arthrosis (OA) is a debilitating disease which increasingly affects the geriatric population. Recent studies have shown that proteoglycan forming cartilage in human tissue is citrullinated in osteoarthritic patients and this could be the cause for the enhanced fragility in the knee joints, leading to fractures and falls. The flexibility of citrulline could be reduced compared to that of arginine as citrulline presents incorporations of rigid nitric elements as well as “condensed” proline atoms, making it resemble a metabolic byproduct of collagen and arginine. In truth, citrulline derives from the activity of multiple enzymes, both aggrecanase and arginase-1. The commentary describes causal involvement of citrullination in OA and also indicates potential therapeutic approaches to how displacing the pathological citrullinated arginine, could help patients with OA.

The Primary Physiological Roles of Autoinducer 2 in Escherichia coli Are Chemotaxis and Biofilm Formation

Autoinducer 2 (AI-2) is a ubiquitous metabolite but, instead of acting as a “universal signal,” relatively few phenotypes have been associated with it, and many scientists believe AI-2 is often a metabolic byproduct rather than a signal. Here, the aim is to present evidence that AI-2 influences both biofilm formation and motility (swarming and chemotaxis), using Escherichia coli as the model system, to establish AI-2 as a true signal with an important physiological role in this bacterium. In addition, AI-2 signaling is compared to the other primary signal of E. coli, indole, and it is shown that they have opposite effects on biofilm formation and virulence.

Engineering lithoheterotrophy in an obligate chemolithoautotrophic Fe(II) oxidizing bacterium

Neutrophilic Fe(II) oxidizing bacteria like Mariprofundus ferrooxydans are obligate chemolithoautotrophic bacteria that play an important role in the biogeochemical cycling of iron and other elements in multiple environments. These bacteria generally exhibit a singular metabolic mode of growth which prohibits comparative “omics” studies. Furthermore, these bacteria are considered non-amenable to classical genetic methods due to low cell densities, the inability to form colonies on solid medium, and production of copious amounts of insoluble iron oxyhydroxides as their metabolic byproduct. Consequently, the molecular and biochemical understanding of these bacteria remains speculative despite the availability of substantial genomic information. Here we develop the first genetic system in neutrophilic Fe(II) oxidizing bacterium and use it to engineer lithoheterotrophy in M. ferrooxydans, a metabolism that has been speculated but not experimentally validated. This synthetic biology approach could be extended to gain physiological understanding and domesticate other bacteria that grow using a single metabolic mode.

Engineering lithoheterotrophy in an obligate chemolithoautotrophic Fe(II) oxidizing bacterium

ABSTRACTNeutrophilic Fe(II) oxidizing bacteria like Mariprofundus ferrooxydans are obligate chemolithoautotrophic bacteria that play an important role in the biogeochemical cycling of iron and other elements in multiple environments. These bacteria generally exhibit a singular metabolic mode of growth which prohibits comparative “omics” studies. Furthermore, these bacteria are considered non-amenable to classical genetic methods due to low cell densities, the inability to form colonies on solid medium, and production of copious amounts of insoluble iron oxyhydroxides as their metabolic byproduct. Consequently, the functional understanding of these bacteria remains speculative despite the availability of substantial genomic information. Here we develop the first genetic system in neutrophilic Fe(II) oxidizing bacterium and use it to engineer lithoheterotrophy in M. ferrooxydans, a metabolism that has been speculated but not experimentally validated. Our work suggests that M. ferroxydans partitions energy generation from carbon oxidation. This synthetic biology approach could be extended to gain physiological understanding and domesticate other bacteria that grow using a single metabolic mode.

Zearalenone Mycotoxicosis: Pathophysiology and Immunotoxicity

Mycotoxicosis refers to the deleterious pathological effects of different types toxins produced by some worldwide distributing fungi. Mycotoxins, as secondary metabolites are affecting different organs and systems both in animal and human beings. Zeralenone (ZEA), the well-known estrogenic mycotoxins, is an immunotoxic agent. This macrocyclic beta-resorcyclic acid lactone, is mycotoxin procreated as a secondary metabolic byproduct by several types of Fusarium, encompassing F. roseum,F. culmorum, F. graminearum and different other types. Attributing to its potent estrogenic activity, ZEA has been incriminated as one of the major causes of female reproductive disorders. Thus, the purpose of the present review article is to appraise the pathophysiological consequences and sub sequent explore the progress in the research field of zearalenone immunotoxicities.

Mrr1 regulation of methylglyoxal catabolism and methylglyoxal-induced fluconazole resistance in Candida lusitaniae

In Candida species, the transcription factor Mrr1 regulates azole resistance genes in addition to the expression of a suite of other genes including known and putative methylglyoxal reductases. Methylglyoxal (MG) is a toxic metabolic byproduct that is significantly elevated in certain disease states that frequently accompany candidiasis, including diabetes, kidney failure, sepsis, and inflammation. Through the genetic analysis of Candida lusitaniae (syn. Clavispora lusitaniae) strains with different Mrr1 variants with high and low basal activity, we showed that Mrr1 regulates basal and/or induced expression of two highly similar MG reductases, MGD1 and MGD2, and that both participate in MG detoxification and growth on MG as a sole carbon source. We found that exogenous MG increases Mrr1-dependent expression of MGD1 and MGD2 in C. lusitaniae suggesting that Mrr1 is part of the natural response to MG. MG also induced expression of MDR1, which encodes a major facilitator protein involved in fluconazole resistance, in a partially Mrr1-dependent manner. MG significantly improved growth of C. lusitaniae in the presence of fluconazole and strains with hyperactive Mrr1 variants showed greater increases in growth in the presence of fluconazole by MG. In addition to the effects of exogenous MG, we found knocking out GLO1, which encodes another MG detoxification enzyme, led to increased fluconazole resistance in C. lusitaniae. Analysis of isolates other Candida species found heterogeneity in MG resistance and MG stimulation of growth in the presence of fluconazole. Given the frequent presence of MG in human disease, we propose that induction of MDR1 in response to MG is a novel contributor to in vivo resistance of azole antifungals in multiple Candida species.Author SummaryIn Candida species, constitutively active variants of the transcription factor Mrr1 confer resistance to fluconazole, a commonly used antifungal agent. However, the natural role of Mrr1 as well as how its activity is modulated in vivo remain poorly understood. Here, we have shown that, in the opportunistic pathogen Candida lusitaniae, Mrr1 regulates expression and induction of two enzymes that detoxify methylglyoxal, a toxic metabolic byproduct. Importantly, serum methylglyoxal is elevated in conditions that are also associated with increased risk of colonization and infection by Candida species, such as diabetes and kidney failure. We discovered that methylglyoxal causes increased expression of these two Mrr1-regulated detoxification enzymes as well as an efflux pump that causes fluconazole resistance. Likewise, methylglyoxal increased the ability of multiple C. lusitaniae strains to grow in the presence of fluconazole. Several other Candida strains that we tested also exhibited stimulation of growth on fluconazole by methylglyoxal. Given the physiological relevance of methylglyoxal in human disease, we posit that the induction of fluconazole resistance in response to methylglyoxal may contribute to treatment failure.

Structure of the novel monomeric glyoxalase I fromZea mays

The glyoxalase system is ubiquitous among all forms of life owing to its central role in relieving the cell from the accumulation of methylglyoxal, a toxic metabolic byproduct. In higher plants, this system is upregulated under diverse metabolic stress conditions, such as in the defence response to infection by pathogenic microorganisms. Despite their proven fundamental role in metabolic stresses, plant glyoxalases have been poorly studied. In this work, glyoxalase I fromZea mayshas been characterized both biochemically and structurally, thus reporting the first atomic model of a glyoxalase I available from plants. The results indicate that this enzyme comprises a single polypeptide with two structurally similar domains, giving rise to two lateral concavities, one of which harbours a functional nickel(II)-binding active site. The putative function of the remaining cryptic active site remains to be determined.

Methanogens in the Environment: An Insight of Methane Yield and Impact on Global Climate Change

Methane is a most important greenhouse gas for planetary heating and it’s produced by methanogenic microorganisms as a metabolic byproduct and creates climate change. Methanogens are ancient organisms on earth found in anaerobic environments and methane is a key greenhouse gas concerned with methanogens. Therefore here is intense interest to writing this paper. A number of experiments have already conducted to study the methanogens in various environments such as rumen and intestinal system of animals, fresh water and marine sediments, swamps and marshes, hot springs, sludge digesters, and within anaerobic protozoa which utilize carbon dioxide in the presence of hydrogen and produce methane. The diversity of methanogens, belong to the domain Archaea and get involved in biological production of methane that catalyzes the degradation of organic compound as a part of global carbon cycle called methanogenesis. Majorly in this article we summaries the diversity of methanogens and their impact on global warming.