- Host Response to Biomaterials

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced “hypothalamic amenorrhea” in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the “dysregulated host response to infection”. They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value.

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Charged Residues Flanking the Transmembrane Domain of Two Related Toxin–Antitoxin System Toxins Affect Host Response

Toxins ◽

10.3390/toxins13050329 ◽

2021 ◽

Vol 13 (5) ◽

pp. 329

Author(s):

Andrew Holmes ◽

Jessie Sadlon ◽

Keith Weaver

Keyword(s):

Amino Acid ◽

Enterococcus Faecalis ◽

Host Response ◽

Cytoplasmic Membrane ◽

Transmembrane Domain ◽

The Other ◽

Type I ◽

Transcriptomic Response ◽

Specific Amino Acid ◽

Transporter Protein

A majority of toxins produced by type I toxin–antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

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