MazEF Toxin-Antitoxin systems: their role in Mycobacterium tuberculosis stress response and drug resistance
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Clostridium perfringens
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Clostridium perfringens
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Toxin/antitoxin (TA) systems are used primarily to inhibit phage, reduce metabolic activity during stress, and maintain genetic elements. Given the extreme toxicity of some of the toxins of these TA systems, we were curious how the cell silences toxins, if the antitoxin is inactivated or when toxins are obtained without antitoxins via horizontal gene transfer. Here we find that the RalR (type I), MqsR (type II), GhoT (type V), and Hha (type VII) toxins are inactivated primarily by a mutation that inactivates the toxin promoter or via the chromosomal mutations iraM and mhpR.
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Horizontal Gene Transfer
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Summary Live cultures, whole killed cultures, washed killed cultures, washings of live cultures, washings of killed cultures and toxin (meningococcus bouillon filtrate) have more or less of a similar effect when injected intracisternally in 250-gram guinea pigs. Experimental meningococcus antitoxin has a neutralizing effect against meningococcus toxin, the washings of killed cultures and to some degree against washed cultures, when mixed with these substances before injection, but shows no evidence of neutralizing live cultures or killed cultures when the mixtures are injected intracisternally. Antimeningococcic serum has evidenced some neutralizing effect against meningococcus toxin when the mixture of toxin and serum was injected intracisternally. Exposure for two hours at incubator temperature has no appreciable deleterious effect on the toxin or mixtures of toxin and antitoxin.
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The development of antitoxin in the bodies of animals injected with diphtheria toxin is one of the best established of facts. Since von Behring and Roux announced the results of their investigations, large numbers of horses have been injected with toxin and have developed abundant antitoxin. Unaltered diphtheria toxin has been used also as a stimulating injection in man, but it has to be used in very small and repeated doses; otherwise it would produce annoying local reactions and possibly even paralysis. It was early realized that if we ever attempted actively to immunize children, the advantage would be great if we could replace pure toxin with an altered toxin which would be equally effective and without danger.
USE OF TOXIN MODIFIED BY ANTITOXIN FOR ACTIVE IMMUNIZATION IN ANIMALS
The earliest knowledge that injections of toxin almost neutralized by antitoxin are capable of stimulating in animals the production of antitoxinAntitoxin
Diphtheria Toxin
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Summary Live cultures, whole killed cultures, washed killed cultures, washings of live cultures, washings of killed cultures and toxin (meningococcus bouillon filtrate) have more or less of a similar effect when injected intracisternally in 250-gram guinea pigs. Experimental meningococcus antitoxin has a neutralizing effect against meningococcus toxin, the washings of killed cultures and to some degree against washed cultures, when mixed with these substances before injection, but shows no evidence of neutralizing live cultures or killed cultures when the mixtures are injected intracisternally. Antimeningococcic serum has evidenced some neutralizing effect against meningococcus toxin when the mixture of toxin and serum was injected intracisternally. Exposure for two hours at incubator temperature has no appreciable deleterious effect on the toxin or mixtures of toxin and antitoxin.
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Diphtheria and tetanus toxins can be adsorbed upon collodion particles and can then be neutralized by the adsorption of their antitoxins., When, however, the particles were treated first with tetanus antitoxin and then with tetanus toxin a phenomenon, at first sight paradoxical, appeared, which may be interpreted as the combination of toxin with antitoxin without neutralization. Further observations are presented here. Collodion particles prepared according to Loeb and unconcentrated antitoxic horse serums were used in 3 types of experiment: A—first treatment with the antitoxin, second treatment with the toxin; B—first treatment with normal serum or a non-corresponding antitoxin, second treatment with the toxin; C—treatment with the toxin alone. Tetanus toxin. With antitoxin dilution 1:1 and toxin 1:1 or 1:10, and with antitoxin 1:10 and toxin 1:1 or 1:10, the mice in experiment B showed no symptoms at all; in experiments A and C they either died or had severe symptoms of tetanus. When antitoxin was used in dilution 1:10 and toxin 1:100, the mice in experiments A and B had no symptoms and in experiment C they showed symptoms of tetanus. Diphtheria toxin. Collodion particles treated with diphtheria toxin alone produce a nodule in the skin of guinea pigs, and the skin over the nodule becomes red and scaley 2 or 3 days after the injection. Toxin + antitoxin produces a nodule over which the skin shows no signs of inflammation. With toxin + normal serum the reaction is the same as with toxin alone. If, however, the order of treatment is reversed, that is, if the particles are first treated with anitoxin and then with toxin, the skin in experiment A shows severe inflammation, and in experiment B no inflammation.
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Corynebacterium diphtheriae
Diphtheria Toxin
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ABSTRACT The long-term persistence of Mycobacterium tuberculosis in communities with high tuberculosis prevalence is a serious problem aggravated by the presence of drug-resistant tuberculosis strains. Drug resistance in an individual patient is often discovered only after a long delay, particularly if the diagnosis is based on current culture-based drug sensitivity testing methods. During such delays, the patient may transmit tuberculosis to his or her contacts. Rapid diagnosis of drug resistance would be expected to reduce this transmission and hence to decrease the prevalence of drug-resistant strains. To investigate this quantitatively, a mathematical model was constructed, assuming a homogeneous population structure typical of communities in South Africa where tuberculosis incidence is high. Computer simulations performed with this model showed that current control strategies will not halt the spread of multidrug-resistant tuberculosis in such communities. The simulations showed that the rapid diagnosis of drug resistance can be expected to reduce the incidence of drug-resistant cases provided the additional measure of screening within the community is implemented.
Extensively drug-resistant tuberculosis
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An atypical toxin variant of Clostridium botulinum (strain 657) was isolated from the feces of a 6-week-old female infant whose symptoms and clinical history were consistent with infant botulism. Toxin detected in the feces and the toxin produced by isolates from the feces and from two rectal swabs could be neutralized by type B botulinal antitoxin only at very high ratios of of antitoxin to toxin in the neutralization mixture. One international unit of type B antitoxin neutralized only about 10 lethal doses of 657 toxin as compared with approximately 10,000 lethal doses of conventional type B toxin from the Beans strain. Antitoxin prepared against 657 toxin was 10 times more effective against the conventional toxin than against the homologous toxin. Toxoid-antitoxin-binding studies indicate that both 657 toxin and type B toxin are heterogeneous and that both toxins may contain the same molecular variants, but that the proportions of the variants are different in each.
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Botulism
Clostridium botulinum
Toxoid
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