Microbe Profile: Corynebacterium diphtheriae - an old foe always ready to seize opportunity.

Corynebacterium diphtheriae is a globally important Gram-positive aerobic Actinobacterium capable of causing the toxin-mediated disease, diphtheria. Diphtheria was a major cause of childhood mortality prior to the introduction of the toxoid vaccine, yet it is capable of rapid resurgence following the breakdown of healthcare provision, vaccination or displacement of people. The mechanism and treatment of toxin-mediated disease is well understood, however there are key gaps in our knowledge on the basic biology of C. diphtheriae particularly relating to host colonisation, the nature of asymptomatic carriage, population genomics and host adaptation.

In vivo imaging and noninvasive ablation of pyramidal neurons in adult NEX-CreERT2 mice.

To study the function of individual neurons that are embedded in a complex neural network is difficult in mice. Conditional mutagenesis permits the spatiotemporal control of gene expression including the ablation of cells by toxins. To direct expression of a tamoxifen-inducible variant of Cre recombinase (CreERT2) selectively to cortical neurons, we replaced the coding region of the murine Nex1 gene by CreERT2 cDNA via homologous recombination in embryonic stem cells. When injected with tamoxifen, adult NEX-CreERT2 mice induced reporter gene expression exclusively in projection neurons of the neocortex and hippocampus. By titrating the tamoxifen dosage, we achieved recombination in single cells, which allowed multiphoton imaging of neocortical neurons in live mice. When hippocampal projection neurons were genetically ablated by induced expression of diphteria toxin, within 20 days the inflammatory response included the infiltration of CD3+ T cells. This marks a striking difference from similar studies, in which dying oligodendrocytes failed to recruit cells of the adaptive immune system.

[Changes in myocardial ultrastructure in diphtheria intoxication]. / Dinamika ul'trastruktur miokarda pri difteriinoi intoksikatsii.

A drastic discoordination in the left and right ventricular ultrastructures was observed 72 hours after diphtheria toxin given to rabbits with experimental diphtheria intoxication. This may cause cardiac death in diphtheria intoxication.

Difteria en niños: prevención de miocarditis con carnitina oral asociado al tratamiento estandar / Children diphtheria: prevention of myocarditis using oral carnitine associated to the standard treatment

Para evaluar la eficacia preventiva de la DL-carnitina en el miocardio, se estudiaron 40 niños con difteria, internados en el Servicio de Infecto-contagiosas del Departamento de Pediatría, Hospital Belén, Trujillo-Perú entre 1986 a 1989. Veinte niños recibieron tratamiento estandar (grupo control) y los otros 20 tratamiento estandar + carnitina: 100 mg/k/d, dos dosis por día y por 4 días consecutivos. El compromiso miocárdico se determinó por la clínica, ECG, niveles de TSGO > 60 UK/ml (29 UI) y el promedio en días de estancia hospitalaria. Miocarditis se presentó en 75 por ciento del grupo control (sin carnitina) y en 30 por ciento del grupo experimental (con carnitina), p < 0.01; la estancia hospitalaria fue de 17.5 días en el primero y 10.8 en el segundo, p < 0.005; mientras por gravedad de miocarditis no fue significativo en ambos grupos. Se concluye, que la DL-carnitina oral asociado al tratamiento estandar de la difteria en niños, tiene efecto preventivo de miocarditis

Exacerbation of bacterial toxicity to infant ferrets by influenza virus: possible role in sudden infant death syndrome.

Of several toxins examined, only staphylococcal alpha and gamma toxin, endotoxin, and diphtheria toxins were lethal for 5-day-old ferrets. Their toxicities were enhanced in animals infected at 1 day old with influenza virus, from 3-fold with staphylococcal gamma toxin through 14-fold for staphylococcal alpha toxin, 84-fold for endotoxin, and 219-fold for diphtheria toxin. No increased viral replication occurred in any tissue; thus the effects of the toxins were exacerbated by the infection, not vice versa. Neonates died suddenly without clinical symptoms as in human babies dying from the sudden infant death syndrome (SIDS). Pathologic examination showed inflammation in the upper respiratory tract, lung edema and collapse, and early bronchopneumonia in the toxin- and influenza virus-treated animals but not in those treated with toxin or virus alone. Thus, bacterial toxins could play a role in SIDS, this being more likely with a concomitant influenza virus infection.

[Changes in the activity of lysosomal enzymes and in the indices of cardiac contractile function in experimental diphtheria poisoning in rabbits]. / Izmenenie aktivnosti fermentov lizosom i nekotorykh pokazatelei sokratitel'noi funktsii serdtsa pri éksperimental'noi difteriinoi intoksikatsii u krolikov.

Contractility of the heart ventricles and the activity of N-acetyl-beta-D-galactosaminiidase in fraction of lysosomes of this part of the heart were studied in rabbits with experimental diphtheritic intoxication. Three days after the onset of the process changes in the activity of the enzyme reached maximum and were expressed in increase of values indicating increased transfer of enzymes from the particles into the cytosol. At the same time, values which were evidence of fixation of the enzyme in the lysosomes reduced. Correlation analysis showed that intensified escape of enzymes into the cytoplasm led to weakening of heart contractile function.

[Effect of different doses of diphtheria exotoxin on the properties of L929 and HeLa cells]. / Deistvie razlichnykh doz difteriinogo ekzotoksina na svoistva kletok L929 i HeLa.

Various forms of interaction between diphtheria exotoxin and the continuous L and HeLa cell lines were revealed, depending on its doses: toxic, subtoxic and small (following the subtoxic dose). Cells of the same origin, treated with these doses, develop similar changes in some of their properties, differing only in their "survival" time, the period of adaptation and the time of entering the phase of active proliferation. the systems of cells, having simultaneously low susceptibility to infection with some RNA-containing viruses (L cells with low susceptibility to vesicular stomatitis virus and HeLa cells with low susceptibility to Coxsackie B5 virus) and high susceptibility to repeated treatment with diphtheria exotoxin, have been obtained.

[Several features of cardiac lipid metabolism under conditions of diphteritic intoxication]. / O nekotorykh osobennostiakh metabolizma lipidov serdtsa v usloviiakh difterinoi intoksikatsii

Basing on the collation of data of histochemical and electron-microscopic investigations of the myocardium of rabbits under conditions of diphtherial intoxication and in blocade of the lipolysis processes in the intact and damaged heart, the authors singled out three ways of utilization of lipids by the cardiac muscle. The first way is associated with adsorption of fatty acids from the circulating blood. This way depends on catecholamines and is blocked with nicotinic acid. The second way is determined by splitting of myocardial triacylglycerols. It does not depend on concentrations of catecholamines and can be blocked only following prolonged exposure to nicotinic acid. The third way is associated with intensity of functioning of mitochondria; destruction of the latter brings about liberation of membrane phospholipids which later are transformed into nonesterified fatty acids. This way does not depend on catecholamines and can be inhibited by acid lipids accumulating in the myocardium as a result of impairment of utilization of these lipids.