The Protective Role of Albumin in <i>Clostridium difficile</i> Infection: A Step Toward Solving the Puzzle

Bella, Stefano Di; Masi, Alessandra di; Turla, Simona; Ascenzi, Paolo; Gouliouris, Theodore; Petrosillo, Nicola

doi:10.1017/ice.2015.221

Cited by 17 publications

(18 citation statements)

References 9 publications

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“…Of note, several variables associated with the development of severe CDI (i.e. prior acid suppression, baseline serum albumin 42•5 g/dl) have already been described by other authors, and testify to the role of concomitant medications and nutritional status in influencing the course of the disease, as well as to the possible protective effect exerted by albumin [24,25]. On the other hand, diabetes was apparently protective against severe CDI in our cohort.…”

Section: Discussionsupporting

confidence: 81%

Increasing incidence of Clostridium difficile infections: results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population

et al. 2016

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Limited information is available on the incidence of Clostridium difficile infections (CDIs) in Italian hospitals. In this study, we assessed the changes in the incidence of CDI over a 5-year period in a teaching hospital in Liguria, the Italian region with the oldest population. Secondary endpoints were the development of severe CDI and 30-day mortality. The annual incidence of CDI/10000 patient-days significantly increased from 0·54 in 2010 to 3·04 in 2014 (χ 2 for trend, P < 0·001). The median age of patients with CDI was 81 years. As many as 81% and 89% of these patients had comorbid conditions and previous exposure to antibiotics, respectively. In the multivariate analysis of risk factors for severe CDI, previous therapy with histamine 2 blockers and low serum albumin were associated with severe CDI, while diabetes appeared to be protective. In the multivariate model of risk factors for 30-day mortality, high leukocyte count, low serum albumin, and increased serum creatinine were unfavourably associated with outcome. Strict adherence to infection control measures was of utmost importance to counteract the increasing incidence of CDI in our hospital, particularly because of the advanced age of the patients and their very high frequency of chronic conditions and use of antibiotics, which readily predispose them to the development of CDI.

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Section: Discussionsupporting

confidence: 81%

Increasing incidence of Clostridium difficile infections: results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population

et al. 2016

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“…toward C. difficile TcdA and TcdB (25,26) and S. pyogenes SLO toxins (data here reported), binding of HSA to the GA module of F. magna could provide growing bacteria with FAs and, possibly, other nutrients transported by HSA (52,53). Overall, the selective recognition of bacteria proteins and toxins through domain II of HSA represents a clear example of host-microbe adaptation at the molecular level.…”

supporting

confidence: 51%

“…This event prevents toxins internalization and the consequent cytotoxic and cytopathic effects, both in vitro and in vivo . This provides an explanation for the clinical correlation between CDI severity and hypoalbuminemia ( 25 , 26 ).…”

Section: Introductionmentioning

confidence: 82%

“…In the last years, the hypothesis that HSA is a player in the innate immunity “orchestra” has emerged ( 25 , 26 , 40 ). Previously, we demonstrated that HSA binds C. difficile TcdA and TcdB toxins that reach the bloodstream after being produced in the colon ( 25 , 26 ). Here, we report the in vitro and ex vivo capability of HSA to neutralize the effects of the PFT produced by GAS, i.e., SLO.…”

Section: Discussionmentioning

confidence: 99%

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Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects

Vita

Leboffe

et al. 2020

Front. Immunol.

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The pathogenicity of group A Streptococcus (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic in vivo. Recent evidence suggests that human serum albumin (HSA), the most abundant protein in plasma, is a player in the innate immunity “orchestra.” We previously demonstrated that HSA acts as a physiological buffer, partially neutralizing Clostridioides difficile toxins that reach the bloodstream after being produced in the colon. Here, we report the in vitro and ex vivo capability of HSA to neutralize the cytotoxic and hemolytic effects of SLO. HSA binds SLO with high affinity at a non-conventional site located in domain II, which was previously reported to interact also with C. difficile toxins. HSA:SLO recognition protects HEp-2 and A549 cells from cytotoxic effects and cell membrane permeabilization induced by SLO. Moreover, HSA inhibits the SLO-dependent hemolytic effect in red blood cells isolated from healthy human donors. The recognition of SLO by HSA may have a significant protective role in human serum and sustains the emerging hypothesis that HSA is an important constituent of the innate immunity system.

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“…Our group tested the effect of human serum albumin (1 × 10 −4 M) on CaCo-2 cell line exposed to 16 µg/mL of TcdA or TcdB. The results demonstrated that human serum albumin was capable of reducing cell death in the group exposed to TcdB [ 156 ]. This effect seems to be attributable to the binding between albumin and C. difficile toxins (unpublished data) [ 157 ], and an in vivo application will soon be attempted.…”

Section: Can Toxin-binding Agents Have a Role In Reducing Pathogenmentioning

confidence: 99%

Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects

Bella

Ascenzi

Siarakas

et al. 2016

Toxins

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203

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Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies.

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The Protective Role of Albumin in Clostridium difficile Infection: A Step Toward Solving the Puzzle

Cited by 17 publications

References 9 publications

Increasing incidence of Clostridium difficile infections: results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population

Increasing incidence of Clostridium difficile infections: results from a 5-year retrospective study in a large teaching hospital in the Italian region with the oldest population

Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects

Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects

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