Evidence for lipopolysaccharide as the predominant proinflammatory mediator in supernatants of antibiotic-treated bacteria

Leeson, Michael C.; Fujihara, Yoshihito; Morrison, David C.

doi:10.1128/iai.62.11.4975-4980.1994

Cited by 31 publications

(16 citation statements)

References 27 publications

(28 reference statements)

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“…However, they disregarded the effects of a mixed culture induced in the gut microbiota ecosystem. Soluble components, predominantly LPS, released from bacterial cells into the gut environment are responsible for the majority of inflammatory cytokines secreted [4,11,14,26]. Lamina propria-resident macrophages have been shown to suppress or have anergic responses to LPS stimuli [42,44].…”

Section: Discussionmentioning

confidence: 99%

Effect of Probiotics Lactobacillus and Bifidobacterium on Gut-Derived Lipopolysaccharides and Inflammatory Cytokines: An In Vitro Study Using a Human Colonic Microbiota Model

Rodes

Khan²,

Paul³

et al. 2013

J. Microbiol. Biotechnol.

136

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Gut-derived lipopolysaccharides (LPS) are critical to the development and progression of chronic low-grade inflammation and metabolic diseases. In this study, the effects of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharide and inflammatory cytokine concentrations were evaluated using a human colonic microbiota model. Lactobacillus reuteri, L. rhamnosus, L. plantarum, Bifidobacterium animalis, B. bifidum, B. longum, and B. longum subsp. infantis were identified from the literature for their anti-inflammatory potential. Each bacterial culture was administered daily to a human colonic microbiota model during 14 days. Colonic lipopolysaccharides, and Gram-positive and negative bacteria were quantified. RAW 264.7 macrophage cells were stimulated with supernatant from the human colonic microbiota model. Concentrations of TNF-alpha, IL-1beta, and IL-4 cytokines were measured. Lipopolysaccharide concentrations were significantly reduced with the administration of B. bifidum (-46.45 +/- 5.65%), L. rhamnosus (-30.40 +/- 5.08%), B. longum (-42.50 +/- 1.28%), and B. longum subsp. infantis (-68.85 +/- 5.32%) (p < 0.05). Cell counts of Gram-negative and positive bacteria were distinctly affected by the probiotic administered. There was a probiotic strain-specific effect on immunomodulatory responses of RAW 264.7 macrophage cells. B. longum subsp. infantis demonstrated higher capacities to reduce TNF-alpha concentrations (-69.41 +/- 2.78%; p < 0.05) and to increase IL-4 concentrations (+16.50 +/- 0.59%; p < 0.05). Colonic lipopolysaccharides were significantly correlated with TNF-alpha and IL-1beta concentrations (p < 0.05). These findings suggest that specific probiotic bacteria, such as B. longum subsp. infantis, might decrease colonic lipopolysaccharide concentrations, which might reduce the proinflammatory tone. This study has noteworthy applications in the field of biotherapeutics for the prevention and/or treatment of inflammatory and metabolic diseases.

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Section: Discussionmentioning

confidence: 99%

Effect of Probiotics Lactobacillus and Bifidobacterium on Gut-Derived Lipopolysaccharides and Inflammatory Cytokines: An In Vitro Study Using a Human Colonic Microbiota Model

Rodes

Khan²,

Paul³

et al. 2013

J. Microbiol. Biotechnol.

136

View full text Add to dashboard Cite

show abstract

“…Endotoxin, or lipopolysaccharide, released from the bacterial cell wall is the most important mediator in the pathogenesis of Gram‐negative sepsis [1–10]. Endotoxin release initiates a complex cascade involving production of endogenous mediators by the immune system of the host.…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology of in-vitro induced filaments, spheroplasts and rod-shaped bacteria in neutropenic mice

Buijs

Dofferhoff

Mouton

et al. 2006

Clinical Microbiology and Infection

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This study compared the in-vitro properties and in-vivo effects of Escherichia coli filaments, spheroplasts and normal cells in a murine thigh infection model. E. coli was exposed to ceftazidime, meropenem or saline to obtain filaments, spheroplasts or normal bacilli, which were then injected into neutropenic mice. After 24 h, morphology, CFUs, local and circulating endotoxin levels, cytokine levels and mortality were recorded, and correlations between bacterial and host parameters of infection were investigated. Filaments and spheroplasts contained more endotoxin/CFU than controls. Histological studies showed that morphologically altered bacteria changed into rod-shaped cells in the absence of antibiotics. Bacterial spread to the liver was significantly higher in mice challenged with rod-shaped cells, compared with antibiotic-exposed bacteria (p 0.007). Muscle endotoxin levels correlated significantly with circulating interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, and both pro-inflammatory cytokines were correlated significantly (p 0.011). Despite a tendency toward higher local and systemic concentrations of endotoxin in the filament group, inflammatory responses and survival did not differ between groups. It was concluded that morphologically altered bacteria contain more endotoxin and can regain a rod shape after withdrawal of antibiotics, while non-antibiotic-exposed bacteria show greater spread to the liver. There was a clear intra-individual relationship between local endotoxin, systemic endotoxin, TNF-alpha and IL-6 production, but these parameters did not differ among groups.

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“…The mechanism by which the endotoxin content is enhanced is still unclear [4,5]. Endotoxin, or lipopolysaccharide, is known to be a key mediator in Gram-negative bacterial infections [6][7][8][9][10], and the high endotoxin content of filaments means that there is a risk of delayed, but higher, release of endotoxin during ongoing antibiotic treatment of infections [10][11][12][13][14][15][16]. Each b-lactam agent has a specific binding affinity for different PBPs.…”

mentioning

confidence: 99%

Concentration-dependency of β-lactam-induced filament formation in Gram-negative bacteria

Buijs

Dofferhoff

Mouton³

et al. 2008

Clinical Microbiology and Infection

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Ceftazidime and cefotaxime are beta-lactam antibiotics with dose-related affinities for penicillin-binding protein (PBP)-3 and PBP-1. At low concentrations, these antibiotics inhibit PBP-3, leading to filament formation. Filaments are long strands of non-dividing bacteria that contain enhanced quantities of endotoxin molecules. Higher concentrations of ceftazidime or cefotaxime cause inhibition of PBP-1, resulting in rapid bacterial lysis, which is associated with low endotoxin release. In the present study, 37 isolates of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. were studied over a 4-h incubation period in the presence of eight concentrations of ceftazidime or cefotaxime. As resistance of Gram-negative bacteria is an emerging problem in clinical practice, 14 isolates of E. coli and Klebsiella pneumoniae that produced extended-spectrum beta-lactamases (ESBLs) were also investigated. Morphological changes after exposure to the beta-lactam antibiotics revealed recognisable patterns in various bacterial families, genera and isolates. In general, all isolates of Enterobacteriaceae produced filaments within a relatively small concentration range, with similar patterns for E. coli and K. pneumoniae. Pseudomonas and Acinetobacter spp. produced filaments in the presence of clinically-relevant concentrations of both antibiotics as high as 50 mg/L. In all genera, filament-producing capacity was clearly related to the MIC. Ceftazidime induced filament production in more isolates and over wider concentration ranges than did cefotaxime. Interestingly, ESBL-producing isolates were not protected against filament induction. The induction of filament production may lead to additional risks during empirical treatment of severe infections.

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Evidence for lipopolysaccharide as the predominant proinflammatory mediator in supernatants of antibiotic-treated bacteria

Cited by 31 publications

References 27 publications

Effect of Probiotics Lactobacillus and Bifidobacterium on Gut-Derived Lipopolysaccharides and Inflammatory Cytokines: An In Vitro Study Using a Human Colonic Microbiota Model

Effect of Probiotics Lactobacillus and Bifidobacterium on Gut-Derived Lipopolysaccharides and Inflammatory Cytokines: An In Vitro Study Using a Human Colonic Microbiota Model

Pathophysiology of in-vitro induced filaments, spheroplasts and rod-shaped bacteria in neutropenic mice

Concentration-dependency of β-lactam-induced filament formation in Gram-negative bacteria

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