A new role for heat shock factor 27 in the pathophysiology of Clostridium difficile toxin B.

A new role for heat shock factor 27 in the pathophysiology of Clostridium difficile toxin B. Am J Physiol Gastrointest Liver Physiol. 2019 Nov 11;: Authors: Yanda MK, Guggino WB, Cebotaru L Abstract Clostridium difficile (CD) is a common pathogen that causes severe gastrointestinal inflammatory diarrhea in patients undergoing antibiotic therapy. Its virulence derives from two toxins, toxin CD, A & B (TcdA and TcdB) (10). Among the prime candidates for CD colonization are patients with cystic fibrosis (CF), who are routinely treated with antibiotics and frequently hospitalized. Indeed, ~50% of CF patients are colonized with virulent forms of CD but do not exhibit diarrhea (7, 9, 61). We found that TcdB has global effects on colonic cells, including reducing the steady-state levels of sodium proton exchange regulatory factors (NHERF), reducing the levels of heat shock protein Hsp27, and increasing the fraction of total Hsp27 bound to the cystic fibro-sis transmembrane regulator (CFTR). Also, since some mutations in CFTR seem to be protective, we asked whether CFTR is a target of TcdB. We show here that TcdB increases the maturation of CFTR and transiently increases its function. These combined effects promote increased surface expression of CFTR, resulting in a transient increase in Cl- secretion. This increase is followed by a precipitous decline in both CFTR-dependent Cl- secretion and transepithelial resistance (TER), suggesting...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research