Iodine from bacterial iodide oxidization by Roseovarius spp. inhibits the growth of other bacteria

Microbial activities in brine, seawater, or estuarine mud are involved in iodine cycle. To investigate the effects of the microbiologically induced iodine on other bacteria in the environment, a total of 13 bacteria that potentially participated in the iodide-oxidizing process were isolated from water or biofilm at a location containing 131 μg ml^?1 iodide. Three distinct strains were further identified as Roseovarius spp. based on 16 S rRNA gene sequences after being distinguished by restriction fragment length polymorphism analysis. Morphological characteristics of these three Roseovarius spp. varied considerably across and within strains. Iodine production increased with Roseovarius spp. growth when cultured in Marine Broth with 200 μg ml^?1 iodide (I^?). When 10⁶ CFU/ml Escherichia coli, Pseudomonas aeruginosa, and Bacillus pumilus were exposed to various concentrations of molecular iodine (I₂), the minimum inhibitory concentrations (MICs) were 0.5, 1.0, and 1.0 μg ml^?1, respectively. However, fivefold increases in the MICs for Roseovarius spp. were obtained. In co-cultured Roseovarius sp. IOB-7 and E. coli in Marine Broth containing iodide (I^?), the molecular iodine concentration was estimated to be 0.76 μg ml^?1 after 24 h and less than 50 % of E. coli was viable compared to that co-cultured without iodide. The growth inhibition of E. coli was also observed in co-cultures with the two other Roseovarius spp. strains when the molecular iodine concentration was assumed to be 0.52 μg ml^?1.     

Physicochemical studies of amylose and its derivatives in aqueous solutions: Thermodynamics of the iodine–triiodide complex

Thermodynamic properties of the amylose–iodine–triiodide complex have been studied by spectrophotometry and by calorimetry using previously studied samples of amylose ionic derivatives, carboxymethylamylose and diethylaminoethylamylose. The ratio of triiodide to total molecular iodine ([I₃]_b/[I]_b + [I₂]_b) in the complex is ca. 0.3 over a range of iodide concentration from 10^?5 to 10^?4M, and there is no evidence for an increasing charge at slightly higher iodide concentration. Direct calorimetric experiments have been carried out in different conditions of polymer, iodine, and iodide concentration in order to study the dependence of the heat of the complexation as a function of the above parameters. It is shown that the dependence of the measured ΔH on the iodide concentration simply derives from the rearrangement of the triiodide equilibrium because of the uptake of a fixed ratio of iodine and triiodide molecules in the complex.     

Effect of iron and phagocytosis on murine macrophage activation in vitro

Iron-exposed murine macrophages have a modified bactericidal activity as shown by previous observations. In order to assess the role of iron in macrophage activation, as measured by free radical production and by intracellular bacterial killing, murine peritoneal macrophages were cultivated in the presence of various sources of iron, human iron-saturated transferrin and ammonium ferric citrate, or iron chelators, Desferal, and human Apo-transferrin, and were infected with an enteropathogenic strain ofE. coli. The release of nitrite (NO₂ ^?), and the production of superoxide anion (O₂ ^?) and hydrogen peroxide (H₂O₂) by the phagocytes were measured and compared to the production by uninfected macrophages. The synergistic action with murine r.IFN-γ was also studied in the radical production reaction and for the bactericidal activity of macrophages. Our results show that in vitro phagocytosis ofE. coli induced elevated production of NO₂ ^? and H₂O₂ by macrophages, and that oxygen derivatives were released independently of the presence of added iron or chelator. Despite a phagocytosis-related enhancement of NO₂ ^? release, reactive nitrogen intermediates (RNI) are not directly involved in the bactericidal mechanism, as revealed by increased intracellular killing owing to RNI inhibitors. Moreover, bacterial killing may depend on oxygen derivatives, as suggested by the effect of the antioxidant sodium ascorbate leading to both a diminished H₂O₂ production and a decreased bactericidal activity of macrophages.     

Enzymatic radioiodination of phospholipids catalyzed by lactoperoxidase

Phospholipids were iodinated with iodide by a lactoperoxidase-catalyzed reaction in the presence of controlled amounts of H₂O₂ which were continuously supplied by glucose oxidase + glucose. Different molecular and ionic species of inorganic iodine present in the reaction mixture (i.e., I^?, I₂, I₃^?) were eliminated by thiosulfate reduction to I^? followed by gel filtration on Sephadex LH-20 which separated I^? from the phospholipids completely. Final separation and identification of individual phospholipids were done on a column of silica gel H using a single solvent mixture consisting of CHCl₃:CH₃OH:CH₃COOH:H₂O (25:15:4:2, by volume). Application of phospholipases A₂ and D or transesterification provided evidence to indicate a covalent iodination of the fatty acid moiety of the lipids by the enzymatic process, which apparently is substitution but could also proceed by addition to the double bonds, when present.     

Uptake of iodide in the marine haptophyte Isochrysis sp. (T.ISO) driven by iodide oxidation

Uptake of iodide was studied in the marine microalga Isochrysis sp. (isol. Haines, T.ISO) during short‐term incubations with radioactive iodide (¹²⁵I^?). Typical inhibitors of the sodium/iodide symporter (NIS) did not inhibit iodide uptake, suggesting that iodide is not taken up through this transport protein, as is the case in most vertebrate animals. Oxidation of iodide was found to be an essential step for its uptake by T.ISO and it seemed likely that hypoiodous acid (HOI) was the form of iodine taken up. Uptake of iodide was inhibited by the addition of thiourea and of other reducing agents, like L‐ascorbic acid, L‐glutathione and L‐cysteine and increased after the addition of oxidized forms of the transition metals Fe and Mn. The simultaneous addition of both hydrogen peroxide (H₂O₂) and a known iodide‐oxidizing myeloperoxidase (MPO) significantly increased iodine uptake, but the addition of H₂O₂ or MPO separately, had no effect on uptake. This confirms the observation that iodide is oxidized prior to uptake, but it puts into doubt the involvement of H₂O₂ excretion and membrane‐bound or extracellular haloperoxidase activity of T.ISO. The increase of iodide uptake by T.ISO upon Fe(III) addition suggests the nonenzymatic oxidation of iodide by Fe(III) in a redox reaction and subsequent influx of HOI. This is the first report on the mechanism of iodide uptake in a marine microalga.     

Comparison of oxidative stress induced by ciprofloxacin and pyoverdin in bacteria and in leukocytes to evaluate toxicity

Oxidative stress induced by ciprofloxacin and pyoverdin, a leukotoxic pigment, was studied by comparing their effect in bacteria and leukocytes. Chemiluminescence (CL) assays with lucigenin or luminol were adapted to measure the stimuli of superoxide anion (O₂^?) and other reactive species of oxygen (ROS) in bacteria. Ciprofloxacin principally induced the production of O₂^? in the three species studied: Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. Lucigenin CL assay showed high oxidative stress in S. aureus due to its low superoxide dismutase (SOD) activity, whereas E. coli exhibited important SOD activity, responsible for little production of O₂^? in absence or presence of ciprofloxacin. Reduction of nitroblue of tetrazolium (NBT) was applied. This assay indicated that there was higher oxidative stress in S. aureus and E. faecalis than in E. coli. The comparison of oxidative stress generated in bacteria and leukocytes was used to check the selective toxicity of ciprofloxacin in comparison with pyoverdin. Ciprofloxacin did not generate significant stimuli of O₂^? in neutrophils, while pyoverdin duplicated the production of O₂^?. CL and NBT were useful to study the leukotoxicity of ciprofloxacin. Oxidative stress caused by the antibiotic and the leukotoxic pigment was similar in bacteria. Copyright © 2003 John Wiley & Sons, Ltd.     

The interaction of carboxymethylamylose and diethylaminoethylamylose with iodine

Spectrophotometric titrations of slightly substituted carboxymethylamylose (CM-Amy) and diethylaminoethylamylose (DEAE-Amy) with iodine in the presence of iodide (I₂/I^?) were carried out as a function of iodide concentration, temperature, and polymeric charge. Binding isotherms for the polymer-I₂/I^? complex are reported in terms of an apparent binding constant (K_a) plotted versus degree of saturation of the complex (θ). The dependence of K_a upon polymeric charge is interpreted as evidence for the negatively charged character of the bound species. The cooperative nature of the binding process is evident in the positive slope of K_a vs (θ). Whereas the apparent binding constants and binding cooperativities for the derivatives are smaller than for the amylose-I₂/I^? complex, the binding enthalpies deduced from the temperature dependence of K_a at θ = 0.5 appear to be the same for amylose and CM-Amy. A viscometric titration of fully charged CM-Amy with I₂/I^?, conducted at dialysis equilibrium between the CM-Amy-I₂/I^? solution and the polymer-free solvent phase, disclosed a maximum in the plot of intrinsic viscosity ([η]) vs θ. The increase in [η] at small θ was interpreted as a reflection of polyelectrolyte expansion provoked by absorption of the negatively charged bound species; the subsequent decline in [η] is attributed to stabilization by I₂/I^? of compact helical sequences or to the formation at higher θ of intermolecular aggregates.     

Reactive oxygen and nitrogen species’ effect on <Emphasis Type="Italic">lux</Emphasis>-biosensors based on <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Salmonella typhimurium</Emphasis>

The effect of reactive oxygen and nitrogen species on lux-biosensors based on the Escherichia coli K12 MG1655 and Salmonella typhimurium LT2 host strains was investigated. The bioactivity of exogenous free radicals to the constitutively luminescent E. coli strain with plasmid pXen7 decreased in the order H₂O₂ > OCl^– > NO^? > RОO^? > ONOO^–> O₂^?- while the bioluminescence of S. typhimurium strain transformed with this plasmid decreased in the order NO^? > H₂O₂ > ONOO^– > RОO^? > OCl^– > O₂^?- The cross-reactivity of induced lux-biosensors to reactive oxygen and nitrogen species, the threshold sensitivity and the luminescence amplitude dependences from the plasmid specificity and the host strain were indicated. The biosensors with plasmid pSoxS′::lux possessed a wider range of sensitivity, including H₂O₂ and OCl^–, along with O₂^?- and NO^?. Among the used reactive oxygen and nitrogen species, H₂O₂ showed the highest induction activity concerning to the plasmids pKatG′::lux, pSoxS′::lux and pRecA′::lux. The inducible lux-biosensors based on S. typhimurium host strain possessed a higher sensitivity to the reactive oxygen and nitrogen species in comparison with the E. coli lux-biosensors.     

The Contribution of Superoxide Radical to Cadmium Toxicity in E. coli

Numerous reports suggest the involvement of oxidative stress in cadmium toxicity, but the nature of the reactive species and the mechanism of Cd-induced oxidative damage are not clear. In this study, E. coli mutants were used to investigate mechanisms of Cd toxicity. Effects of Cd on metabolic activity, production of superoxide radical by the respiratory chain, and induction of enzymes controlled by the soxRS regulon were investigated. In E. coli, the soxRS regulon controls defense against O₂·⁻and univalent oxidants. Suppression of metabolic activity, inability of E. coli to adapt to new environment, and slow cell division were among the manifestations of Cd toxicity. Cd increased production of O₂·⁻ by the electron transport chain and prevented the induction of soxRS-controlled protective enzymes, even when the regulon was induced by the redox-cycling agent, paraquat. The effect was not limited to soxRS-dependent proteins and can be attributed to previously reported suppression of protein synthesis by Cd. Increased production of superoxide, combined with inability to express protective enzymes and to replace damaged proteins by de novo protein synthesis, seems to be the main reason for growth stasis and cell death in Cd poisoning.

     

Non-enzymatic formation of sulfenyl iodide by solubilized thyroid particulate protein with peroxidase activity

Thyroidal particulate protein with peroxidase activity has been studied to determined wetherr it could be induced to form a sulfenyl iodide, postulated as a reactive intermediate in the iodination of tyrosine. The protein was solubilized with digitonin and purified by tryptic digestion and filtration through Sephadex G-200. When supplemented with H₂O₂ it catalyzed the oxidation of guaiacol iodide or thiourea at 37°C. With iodide as substrate the product was an iodoprotein. In the absence of H₂O₂ the protein did not bind ¹³¹I^? or thio[¹⁴C] urea unless it first had been dialyzed against [³⁶Cl] chlorinated buffer. During dialysis a portion of the ³⁶Cl from the dialysis medium was bound by protein. Subsequent binding of iodide or thiourea was accompanied by loss of protein-bound ³⁶Cl.Addition of iodide to dialyzed protein at 4°C resulted in formation of a yellow compound with maximum absorbance at 355 nm. It was postulated to be a sulfenyl periodide on the basis of its absorption spectrum and its behavior with thio[¹⁴C] urea and 2-mercaptoethanol. The stability of the colored species was dependent on temperature and concentration of iodide. Disappearance of color as the solution was warmed was accompanied by formation of iodo-protein. Predialysis of the protein against p-chloromercuribenzoate, but not 2-mercaptoethanol or bisulfite, prevented the formation of the yellow proteiniodide species, indicating that a reactive sulfhydryl group was involved in the reaction. It was concluded that a particulate protein closely asscociated with thyroid peroxidase could be induced by non-enzymatic means to form a species which has properties consistent with those of a sulfenyl iodide. Further investigation will be required to determine whether the same protein-iodine species can be identified during the peroxidase-catalyzed oxidation of iodide.     

Availability of iodide and iodate to spinach (Spinacia oleracea L.) in relation to total iodine in soil solution

A greenhouse pot experiment was carried out to investigate the availability of iodide and iodate to soil-grown spinach (Spinacia oleracea L.) in relation to total iodine concentration in soil solution. Four iodine concentrations (0, 0.5, 1, 2 mg kg⁻¹) for iodide (I⁻) and iodate (IO₃⁻) were used. Results showed that the biomass productions of spinach were not significantly affected by the addition of iodate and iodide to the soil, and that iodine concentrations in spinach plants on the basis of fresh weights increased with increasing addition of iodine. Iodine concentrations in tissues were much greater for plants grown with iodate than with iodide. In contrast to the iodide treatments, in iodate treatment leaves accounted for a larger fraction of the total plant iodine. The soil-to-leaf transfer factors (TF_leaf) for plants grown with iodate were about tenfold higher than those grown with iodide. Iodine concentrations in soil solution increased with increasing iodine additions to the soil irrespective of iodine species. However, total iodine in soil solution was generally higher for iodate treatments than iodide both in pots with and without spinach. According to these results, iodate can be considered as potential iodine fertilizer to increase iodine content in vegetables.     

Bactericidal Activity of Catecholamine Copper Complexes

Washed or growing E. coli cells are killed by epinephrine, norepinephrine or dopamine in the presence of non lethal concentrations of Cu(II). Killing is enhanced by anoxia and by sublethal Concentrations of H₂O₁. The rate of killing is proportional to the rate of catecholamine oxidation. The copper epinephrine complex binds to E. coli cells, induces membrane damage and depletion of the cellular ATP pool. The cells may be partially protected by SOD or catalase but not by OH radical scavengers. Addition of H²O₂ to cells which were sensitized by preincubation with the epinephrine-copper complex, causes rapid killing and DNA degradation. Sensitized cells are not protected by BSA.     

Peroxidase-catalyzed halide ion oxidation

Abstract

The first complete mechanistic analysis of halide ion oxidation by a peroxidase was that of iodide oxidation by horseradish peroxidase. It was shown conclusively that a two-electron oxidation of iodide by compound I was occurring. This implied that oxygen atom transfer was occurring from compound I to iodide, forming hypoiodous acid, HOI. Searches were conducted for other two-electron oxidations. It was found that sulfite was oxidized by a two-electron mechanism. Nitrite and sulfoxides were not. If a competing substrate reduces some compound I to compound II by the usual one-electron route, then compound II will compete for available halide. Thus compound II oxidizes iodide to an iodine atom, I^·, although at a slower rate than oxidation of I^- by compound I. An early hint that mammalian peroxidases were designed for halide ion oxidation was obtained in the reaction of lactoperoxidase compound II with iodide. The reaction was accelerated by excess iodide, indicating a co-operative effect. Among the heme peroxidases, only chloroperoxidase (for example from Caldariomyces fumago) and mammalian myeloperoxidase are able to oxidize chloride ion. There is not yet a consensus as to whether the chlorinating agent produced in a peroxidase-catalyzed reaction is hypochlorous acid (HOCl), enzyme-bound hypochlorous acid (either Fe–HOCl or X–HOCl where X is an amino acid residue), or molecular chlorine Cl₂. A study of the non-enzymatic iodination of tyrosine showed that the iodinating reagent was either HOI or I₂. It was impossible to tell which species because of the equilibria:

I₂+H₂O=HOI+I^-+H⁺</ p>

I^-+I₂=I₃^-

The same considerations apply to product analysis of an enzyme-catalyzed reaction. Detection of molecular chlorine Cl₂ does not prove it is the chlorinating species. If Cl₂ is in equilibrium with HOCl then one cannot tell which (if either) is the chlorinating reagent. Examples will be shown of evidence that peroxidase-bound hypochlorous acid is the chlorinating agent. Also a recent clarification of the mechanism of reaction of myeloperoxidase with hydrogen peroxide and chloride along with accurate determination of the elementary rate constants will be discussed.     

Myeloperoxidase-mediated oxidation of methionine

The myeloperoxidase-mediated oxidation of methionine was studied using a purified canine myeloperoxidase preparation. The system required the simultaneous presence of myeloperoxidase, H₂O₂, and a halide anion. When 0.1 mM H₂O₂ was used, the system has a pH optimum of approximately pH 5–5.5. Bromide and iodide were much more effective than chloride in the myeloperoxidase-mediated oxidation of methionine. Horseradish peroxidase was unable to oxidize methionine whether chloride or iodide was used. In contrast, lactoperoxidase oxidized methionine in the presence of iodide but not chloride. Based on studies of (1) the effect of various inhibitors and singlet oxygen quenchers, as well as (2) the effect of D₂O on the oxidation of methionine, by the myeloperoxidase system, OCl^?, or methylene blue, it was shown that the oxidation of methionine by the myeloperoxidase system was not mediated by OCl^? or ¹O₂. The mechanism of the myeloperoxidase-mediated oxidation of methionine remains unclear. However, it may be one mechanism by which the myeloperoxidase system damage microorganisms.     

Oxidative epithelial host defense is regulated by infectious and inflammatory stimuli

Epithelia express oxidative antimicrobial protection that uses lactoperoxidase (LPO), hydrogen peroxide (H₂O₂), and thiocyanate to generate the reactive hypothiocyanite. Duox1 and Duox2, found in epithelia, are hypothesized to provide H₂O₂ for use by LPO. To investigate the regulation of oxidative LPO-mediated host defense by bacterial and inflammatory stimuli, LPO and Duox mRNA were followed in differentiated primary human airway epithelial cells challenged with Pseudomonas aeruginosa flagellin or IFN-γ. Flagellin upregulated Duox2 mRNA 20-fold, but upregulated LPO mRNA only 2.5-fold. IFN-γ increased Duox2 mRNA 127-fold and upregulated LPO mRNA 10-fold. DuoxA2, needed for Duox2 activity, was also upregulated by flagellin and IFN-γ. Both stimuli increased H₂O₂ synthesis and LPO-dependent killing of P. aeruginosa. Reduction of Duox1 by siRNA showed little effect on basal H₂O₂ production, whereas Duox2 siRNA markedly reduced basal H₂O₂ production and resulted in an 8-fold increase in Nox4 mRNA. In conclusion, large increases in Duox2-mediated H₂O₂ production seem to be coordinated with increases in LPO mRNA and, without increased LPO, H₂O₂ levels in airway secretion are expected to increase substantially. The data suggest that Duox2 is the major contributor to basal H₂O₂ synthesis despite the presence of greater amounts of Duox1.     

Superoxide Production by a Manganese-Oxidizing Bacterium Facilitates Iodide Oxidation

The release of radioactive iodine (i.e., iodine-129 and iodine-131) from nuclear reprocessing facilities is a potential threat to human health. The fate and transport of iodine are determined primarily by its redox status, but processes that affect iodine oxidation states in the environment are poorly characterized. Given the difficulty in removing electrons from iodide (I⁻), naturally occurring iodide oxidation processes require strong oxidants, such as Mn oxides or microbial enzymes. In this study, we examine iodide oxidation by a marine bacterium, Roseobacter sp. AzwK-3b, which promotes Mn(II) oxidation by catalyzing the production of extracellular superoxide (O₂⁻). In the absence of Mn²⁺, Roseobacter sp. AzwK-3b cultures oxidized ∼90% of the provided iodide (10 μM) within 6 days, whereas in the presence of Mn(II), iodide oxidation occurred only after Mn(IV) formation ceased. Iodide oxidation was not observed during incubations in spent medium or with whole cells under anaerobic conditions or following heat treatment (boiling). Furthermore, iodide oxidation was significantly inhibited in the presence of superoxide dismutase and diphenylene iodonium (a general inhibitor of NADH oxidoreductases). In contrast, the addition of exogenous NADH enhanced iodide oxidation. Taken together, the results indicate that iodide oxidation was mediated primarily by extracellular superoxide generated by Roseobacter sp. AzwK-3b and not by the Mn oxides formed by this organism. Considering that extracellular superoxide formation is a widespread phenomenon among marine and terrestrial bacteria, this could represent an important pathway for iodide oxidation in some environments.     

Efficiency of KrCl excilamp (222 nm) for inactivation of bacteria in suspension

Aims: To examine the killing efficiency of UV KrCl excilamp against Gram‐positive and Gram‐negative bacteria. Methods and Results: Vegetative cells of Bacillus cereus, Bacillus subtilis, Escherichia coli O157:H7, Staphylococcus aureus and Streptococcus pyogenes at initial populations from 10² to 10⁷ colony‐forming units (CFU) ml^?1 were treated by KrCl excilamp in sterile Ringer’s solution with and without H₂O₂. The number of viable cells was determined using spread plating techniques and nutrient agar method with subsequent incubation at 28°C or 37°C for 24 h. At estimated populations of 10²–10⁵ CFU ml^?1E. coli O157:H7 and Staph. aureus were the most sensitive and showed 100% disinfection within 15 s (29·2 mJ cm^?2). Bacillus subtilis was more sensitive to UV treatment than B. cereus. The UV/H₂O₂ inactivation rate coefficients within this population range were two times higher than those observed for UV treatment alone. No effect of H₂O₂ was observed at 10⁷ CFU ml^?1 for Bacillus sp. and Strep. pyogenes. Conclusions: The narrow‐band UV radiation at 222 nm was effective in the rapid disinfection of bacteria in aqueous suspensions. Significance and Impact of the Study: KrCl excilamps represent UV sources which can be applied for disinfection of drinking water in advanced oxidation processes.     

Biogenic Manganese Oxides Facilitate Iodide Oxidation at pH ≤ 5

Radioactive ¹²⁹I, a byproduct of nuclear power generation, can pose risks to human health if released into the environment, where its mobility is highly dependent on speciation. Based on thermodynamic principles, ¹²⁹I should exist primarily as iodide (I^?) in most terrestrial environments; however, organo-¹²⁹I and ¹²⁹iodate are also commonly detected in contaminated soils and groundwater. To investigate the capability of biogenic manganese oxides to influence iodide speciation, 17 manganese-oxidizing bacterial strains, representing six genera, were isolated from soils of the Savannah River Site, South Carolina. The isolates produced between 2.6 and 67.1 nmole Mn oxides (ml^?1 media after 25 days, pH 6.5). Results from inhibitor assays targeting extracellular enzymes and reactive oxygen species indicated that both play a role in microbe-induced Mn(II) oxidation among the strains examined. Iodide oxidation was not observed in cultures of the most active Mn-oxidizing bacteria, Chryseobacterium sp. strain SRS1 and Chromobacterium sp. strain SRS8, or the fungus, Acremonium strictum strain KR21–2. While substantial amounts of Mn(III/IV) oxides were only generated in cultures at ≥pH 6, iodide oxidation was only observed in the presence of Mn(III/IV) oxides when the pH was ≤5. Iodide oxidation was promoted to a greater extent by synthetic Mn(IV)O₂ than biogenic Mn(III/IV) oxides under these low pH conditions (≤pH 5). These results indicate that the influence of biogenic manganese oxides on iodide oxidation and immobilization is primarily limited to low pH environments.     

Hypothiocyanite and host–microbe interactions

The pseudohypohalous acid hypothiocyanite/hypothiocyanous acid (OSCN⁻/HOSCN) has been known to play an antimicrobial role in mammalian immunity for decades. It is a potent oxidant that kills bacteria but is non-toxic to human cells. Produced from thiocyanate (SCN⁻) and hydrogen peroxide (H₂O₂) in a variety of body sites by peroxidase enzymes, HOSCN has been explored as an agent of food preservation, pathogen killing, and even improved toothpaste. However, despite the well-recognized antibacterial role HOSCN plays in host–pathogen interactions, little is known about how bacteria sense and respond to this oxidant. In this work, we will summarize what is known and unknown about HOSCN in innate immunity and recent advances in understanding the responses that both pathogenic and non-pathogenic bacteria mount against this antimicrobial agent, highlighting studies done with three model organisms, Escherichia coli, Streptococcus spp., and Pseudomonas aeruginosa.     

Different Susceptibility of Three Clinically Isolated Strains of Cryptococcus neoformans to the Fungicidal Effects of Reactive Nitrogen and Oxygen Intermediates: Possible Relationships with Virulence

We investigated the susceptibility of three clinically isolated strains of Cryptococcus neoformans with different virulences to reactive nitrogen and oxygen intermediates (RNI and ROI, respectively), representing two important mediators of macrophage microbicidal activity. All mice infected with the highly virulent strain of C. neoformans, YC-11, died within 3 to 6 weeks because of rapid multiplication of the organism in the lungs and dissemination to the brain. In contrast, a weakly virulent strain, YC-13, was almost completely eradicated from the lungs and did not disseminate to the brain, leading to survival of all infected animals during the period of observation (15 weeks). The virulence of the third strain, YC-5, was intermediate between the other two strains. To examine the susceptibility of C. neoformans to the fungicidal effect of nitric oxide (NO) and superoxide anions (O₂-), the organisms were exposed to these oxidants, which were chemically generated in a cell-free system. Interestingly, the number of live YC-13 yeast cells was markedly reduced after exposure to NO and O₂^?. In contrast, YC-11 was almost completely resistant to the killing effect of these oxidants. YC-5 showed an intermediate susceptibility. Our results demonstrate that the resistance of C. neoformans to the fungicidal effects of RNI and ROI is related to virulence, and suggest that the resistance to nitrogen- and oxygen-derived oxidants may be one of the factors to determine the outcome of infection with C. neoformans.