Effect of catalase on CIR resistance.

<p><b>a</b>: Growth of DR and DR<i>kat</i>^- under 36 Gy/h, or without CIR. Dilutions of DR and DR<i>kat</i>^- are indicated. <b>b</b>: Growth restoration of DR<i>kat</i>^- under 36 Gy/h by catalase, added to the central area of a TGY plate that was pre-inoculated with DR<i>kat</i>^- cells. Dilutions (log₁₀ based) of inoculated DR<i>kat</i>^- are indicated.</p

Comparison of observed and model-predicted growth-inhibitory critical CIR dose rates for microorganisms grown under aerobic conditions.

<p><b>a</b>: Bacteria. <b>b</b>: Fungi. Green diamonds: <i>highest</i> tested dose rate at which <i>any</i> growth was observed. Red squares: <i>lowest</i> tested dose rate at which <i>no</i> growth was observed. Blue curves: best-fit model predictions. Black points: uncertainty range of model predictions. Model-based predictions at cell concentrations higher than those tested had very large uncertainties for EC2 and SC and, therefore, the prediction curves were truncated at cell concentrations slightly above 0 dilution for these organisms.</p

A schematic representation of the effects of cell concentration on microbial resistance to CIR.

<p>A schematic representation of the effects of cell concentration on microbial resistance to CIR.</p

Confidence intervals (95% CIs) for best-fit model parameter values.

<p>Confidence intervals (95% CIs) for best-fit model parameter values.</p

Microbial cooperation under CIR.

<p><b>a</b>: Growth of EC1 in the presence or absence of 36 Gy/h for 2 days, either in pure culture or mixed in 1:1 co-culture with DR. <b>b</b>: As for panel A, but with DR<i>kat</i>^- substituting for DR. The y-axis shows clonogenically viable cell concentrations normalized to 1 ml: the actual numbers of viable cells are 200 times smaller because only 5 μl of each species were used in these experiments. Dashed lines indicate cell concentrations under the assumption of no net proliferation.</p

Aerobic growth of microorganisms under CIR.

<p><b>a:</b> Bacteria. <b>b:</b> Clonogenic survival of bacteria under CIR. For the corresponding CIR study under microaerobic conditions, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189261#pone.0189261.s002" target="_blank">S1 Fig</a>. In this and the following figure, dilutions shown in panels <b>a</b> and <b>c</b> are on a log₁₀ scale and represent order of magnitude changes in initial cell concentration. The bars shown in panel <b>b</b> are based on CFU counts normalized to 1 ml: the actual numbers of viable cells are 200 times smaller because only 5 μl of each species were used in these experiments. At 94 Gy/h, individual colonies could not always be reliably identified, and therefore the bars at this dose rate represent estimates. Abbreviations: No IR = no irradiation; sealed = microaerobic. Red arrows indicate cases where 10-fold reduction in cell concentration completely extinguished growth at a given dose rate. <b>c:</b> Fungi.</p

ORAC of TGY harvested with or without bacterial growth.

<p><b>a</b>: The net AUC (net area under the fluorescence decay curve) is an integrative value of total fluorescence during antioxidant reaction in the presence of the indicated sample. <b>b:</b> Linear regression for log-transformed ratios of net AUC for samples with indicated bacteria to samples without bacteria, vs. log-transformed time. Red lines = regression best fits, blue lines = 95% confidence intervals. Y-axis values >0 suggest that the indicated microorganisms increased the ORAC of the medium; values <0 suggest the opposite—microorganisms decreased the ORAC.</p

Quantification of responses to AIR and CIR for fungi.

<p>Logistic regression intended to predict growth at 36 Gy/h based on log₁₀[D₁₀]. D₁₀ = AIR dose which kills 90% of population. Growth at 36 Gy/h was a binary variable (0 = no growth, 1 = growth). Blue circles indicate raw data; Black squares indicate summary data for log₁₀[D₁₀] quartiles, where x-axis shows median log₁₀[D₁₀] values for each quartile and y-axis shows fractions of fungi which grew under 36 Gy/h; Red curve = best-fit model predictions.</p

MDP: A <i>Deinococcus</i> Mn²⁺-Decapeptide Complex Protects Mice from Ionizing Radiation

<div><p>The radioprotective capacity of a rationally-designed Mn²⁺-decapeptide complex (MDP), based on Mn antioxidants in the bacterium <i>Deinococcus radiodurans</i>, 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 <i>in vitro</i> for their ability to protect cultured human cells and purified enzymes from extreme damage caused by ionizing radiation (IR). We show that the peptides accumulated in Jurkat T-cells and protected them from 100 Gy. MDP preserved the activity of T4 DNA ligase exposed to 60,000 Gy. <i>In vivo</i>, MDP was nontoxic and protected B6D2F1/J (female) mice from acute radiation syndrome. All irradiated mice treated with MDP survived exposure to 9.5 Gy (LD_70/30) in comparison to the untreated mice, which displayed 63% lethality after 30 days. Our results show that MDP provides early protection of white blood cells, and attenuates IR-induced damage to bone marrow and hematopoietic stem cells via G-CSF and GM-CSF modulation. Moreover, MDP mediated the immunomodulation of several cytokine concentrations in serum including G-CSF, GM-CSF, IL-3 and IL-10 during early recovery. Our results present the necessary prelude for future efforts towards clinical application of MDP as a promising IR countermeasure. Further investigation of MDP as a pre-exposure prophylactic and post-exposure therapeutic in radiotherapy and radiation emergencies is warranted.</p></div

MDP administration modulates cytokine response <i>in vivo</i>.

<p>Modulation of cytokines in the serum of irradiated mice on days 3 and 30 was evaluated by Luminex multiplex. (A) G-CSF level. (B) GM-CSF level. (C) IL-3 level. (D) IL-10 levels. IR exposure dose was 9.5 Gy. *<i>p</i> < 0.05 vs. Veh+Sham; ^<i>p</i> < 0.05 vs. Veh+IR. Abbreviation: Veh, vehicle.</p