radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology.

The bacterium responsible for Lyme disease, , accumulates high levels of manganese without iron and possesses a polyploid genome, characteristics suggesting potential extreme resistance to radiation. Contrary to expectations, we report that wild-type B31 cells are radiosensitive, with a gamma-radiation survival limit for 10 wild-type cells of <1 kGy. Thus, we explored radiosensitivity through electron paramagnetic resonance (EPR) spectroscopy by quantitating the fraction of Mn present as antioxidant Mn metabolite complexes (H-Mn).

Irradiated whole cell Chlamydia vaccine confers significant protection in a murine genital tract challenge model.

Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm).

Effects of Desiccation and Freezing on Microbial Ionizing Radiation Survivability: Considerations for Mars Sample Return.

Increasingly, national space agencies are expanding their goals to include Mars exploration with sample return. To better protect Earth and its biosphere from potential extraterrestrial sources of contamination, as set forth in the Outer Space Treaty of 1967, international efforts to develop planetary protection measures strive to understand the danger of cross-contamination processes in Mars sample return missions. We aim to better understand the impact of the martian surface on microbial dormancy and survivability.

Small-Molecule Mn Antioxidants in Caenorhabditis elegans and Deinococcus radiodurans Supplant MnSOD Enzymes during Aging and Irradiation.

Denham Harman's oxidative damage theory identifies superoxide (O) radicals as central agents of aging and radiation injury, with Mn-dependent superoxide dismutase (MnSOD) as the principal O-scavenger. However, in the radiation-resistant nematode Caenorhabditis elegans, the mitochondrial antioxidant enzyme MnSOD is dispensable for longevity, and in the model bacterium Deinococcus radiodurans, it is dispensable for radiation resistance. Many radiation-resistant organisms accumulate small-molecule Mn-antioxidant complexes well-known for their catalytic ability to scavenge O, along with MnSOD, as exemplified by D.

Radiation-Inactivated Vaccine Candidates.

is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved.

A novel gamma radiation-inactivated sabin-based polio vaccine.

A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts.

Prospects for Fungal Bioremediation of Acidic Radioactive Waste Sites: Characterization and Genome Sequence of MD1149.

Highly concentrated radionuclide waste produced during the Cold War era is stored at US Department of Energy (DOE) production sites. This radioactive waste was often highly acidic and mixed with heavy metals, and has been leaking into the environment since the 1950s. Because of the danger and expense of cleanup of such radioactive sites by physicochemical processes, bioremediation methods are being developed for cleanup of contaminated ground and groundwater.

Microbial cells can cooperate to resist high-level chronic ionizing radiation.

Understanding chronic ionizing radiation (CIR) effects is of utmost importance to protecting human health and the environment. Diverse bacteria and fungi inhabiting extremely radioactive waste and disaster sites (e.g.

MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation.

The radioprotective capacity of a rationally-designed Mn2+-decapeptide complex (MDP), based on Mn antioxidants in the bacterium Deinococcus radiodurans, was investigated in a mouse model of radiation injury. MDP was previously reported to be extraordinarily radioprotective of proteins in the setting of vaccine development. The peptide-component (DEHGTAVMLK) of MDP applied here was selected from a group of synthetic peptides screened in vitro for their ability to protect cultured human cells and purified enzymes from extreme damage caused by ionizing radiation (IR).

Responses of Mn2+ speciation in Deinococcus radiodurans and Escherichia coli to γ-radiation by advanced paramagnetic resonance methods.

The remarkable ability of bacterium Deinococcus radiodurans to survive extreme doses of γ-rays (12,000 Gy), 20 times greater than Escherichia coli, is undiminished by loss of Mn-dependent superoxide dismutase (SodA). D. radiodurans radiation resistance is attributed to the accumulation of low-molecular-weight (LMW) "antioxidant" Mn(2+)-metabolite complexes that protect essential enzymes from oxidative damage.

Effects of Mn and Fe levels on Bacillus subtilis spore resistance and effects of Mn2+, other divalent cations, orthophosphate, and dipicolinic acid on protein resistance to ionizing radiation.

Spores of Bacillus subtilis strains with (wild type) or without (α(-)β(-)) most DNA-binding α/β-type small, acid-soluble proteins (SASP) were prepared in medium with additional MnCl(2) concentrations of 0.3 μM to 1 mM. These haploid spores had Mn levels that varied up to 180-fold and Mn/Fe ratios that varied up to 300-fold.

Small-molecule antioxidant proteome-shields in Deinococcus radiodurans.

For Deinococcus radiodurans and other bacteria which are extremely resistant to ionizing radiation, ultraviolet radiation, and desiccation, a mechanistic link exists between resistance, manganese accumulation, and protein protection. We show that ultrafiltered, protein-free preparations of D. radiodurans cell extracts prevent protein oxidation at massive doses of ionizing radiation.

Protein oxidation: key to bacterial desiccation resistance?

For extremely ionizing radiation-resistant bacteria, survival has been attributed to protection of proteins from oxidative damage during irradiation, with the result that repair systems survive and function with far greater efficiency during recovery than in sensitive bacteria. Here we examined the relationship between survival of dry-climate soil bacteria and the level of cellular protein oxidation induced by desiccation. Bacteria were isolated from surface soils of the shrub-steppe of the US Department of Energy's Hanford Site in Washington State.

Deinococcus geothermalis: the pool of extreme radiation resistance genes shrinks.

Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D.

Protein oxidation implicated as the primary determinant of bacterial radioresistance.

In the hierarchy of cellular targets damaged by ionizing radiation (IR), classical models of radiation toxicity place DNA at the top. Yet, many prokaryotes are killed by doses of IR that cause little DNA damage. Here we have probed the nature of Mn-facilitated IR resistance in Deinococcus radiodurans, which together with other extremely IR-resistant bacteria have high intracellular Mn/Fe concentration ratios compared to IR-sensitive bacteria.

Comparative genomics of Thermus thermophilus and Deinococcus radiodurans: divergent routes of adaptation to thermophily and radiation resistance.

Background: Thermus thermophilus and Deinococcus radiodurans belong to a distinct bacterial clade but have remarkably different phenotypes. T. thermophilus is a thermophile, which is relatively sensitive to ionizing radiation and desiccation, whereas D.

How radiation kills cells: survival of Deinococcus radiodurans and Shewanella oneidensis under oxidative stress.

We have recently shown that Deinococcus radiodurans and other radiation resistant bacteria accumulate exceptionally high intracellular manganese and low iron levels. In comparison, the dissimilatory metal-reducing bacterium Shewanella oneidensis accumulates Fe but not Mn and is extremely sensitive to radiation. We have proposed that for Fe-rich, Mn-poor cells killed at radiation doses which cause very little DNA damage, cell death might be induced by the release of Fe(II) from proteins during irradiation, leading to additional cellular damage by Fe(II)-dependent oxidative stress.

Hyaluronic acid facilitates the recovery of hematopoiesis following 5-fluorouracil administration.

The fate of hematopoietic stem cells (HSCs) is determined by microenvironmental niches, but the molecular structure of these local networks is not yet completely characterized. Our recent observation that glycosaminoglycan hyaluronic acid (HA), a major component of the bone marrow extracellular matrix, is required for in vitro hematopoiesis led us to suggest a role for HA in structuring the hematopoietic niche. Accordingly, HA deprivation induced by various treatments might lead to an imbalance of normal HSC homeostasis.

Expression of Birt-Hogg-Dubé gene mRNA in normal and neoplastic human tissues.

Birt-Hogg-Dubé (BHD) syndrome is an inherited autosomal genodermatosis characterized by hamartomas of the hair follicle called fibrofolliculomas and an increased risk for developing spontaneous pneumothorax, lung cysts and renal neoplasia. BHD was localized to chromosome 17p11.2 by linkage analysis in BHD families, and germline insertion/deletion and nonsense mutations in a novel gene were identified which were predicted to prematurely truncate the BHD protein, folliculin.

A Role of Endogenous Retroviral MCF env Gene in Proliferation of Pluripotent Hemopoietic Progenitors in Mice.

We have investigated the role of endogenous retroviral mink cell focus-forming (MCF) genes in the regulation of mouse bone marrow hemopoietic progenitor cell proliferation. The p15E protein coded by the MCF env gene is expressed by early hemopoietic progenitors, mostly on spleen colony forming units (CFUs-12) and on erythropoietin-independent erythroid progenitors. Stimulation of cell proliferation in hemopoietic precursors by steroid hormone (testosterone propionate) treatment resulted in upregulation of the expression of the endogenous p15E protein on bone marrow cells.