scholarly journals LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.

1998 ◽  
Vol 101 (10) ◽  
pp. 2065-2071 ◽  
Author(s):  
N Lamping ◽  
R Dettmer ◽  
N W Schröder ◽  
D Pfeil ◽  
W Hallatschek ◽  
...  
Keyword(s):  
Septic Shock ◽  
Binding Protein ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Lps Binding

scholarly journals Interaction of Antimicrobial Peptide Temporin L with Lipopolysaccharide In Vitro and in Experimental Rat Models of Septic Shock Caused by Gram-Negative Bacteria

2006 ◽  
Vol 50 (7) ◽  
pp. 2478-2486 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Federico Mocchegiani ◽  
Fiorenza Orlando ◽  
...  
Keyword(s):  
Septic Shock ◽  
Antimicrobial Peptide ◽  
Gram Negative Bacteria ◽  
Amphibian Skin ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Rat Models ◽  
E Coli ◽  
Tnf Α

ABSTRACT Sepsis remains a major cause of morbidity and mortality in hospitalized patients, despite intense efforts to improve survival. The primary lead for septic shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the quest for compounds with antiendotoxin properties is actively pursued. We investigated the efficacy of the amphibian skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro and counteracting its effects in vivo. Temporin L strongly bound to purified E. coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity of temporin L against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide's affinity for endotoxin. Antimicrobial assays showed that temporin L interacted synergistically with the clinically used β-lactam antibiotics piperacillin and imipenem. Therefore, we characterized the activity of temporin L when combined with imipenem and piperacillin in the prevention of lethality in two rat models of septic shock, measuring bacterial growth in blood and intra-abdominal fluid, endotoxin and tumor necrosis factor alpha (TNF-α) concentrations in plasma, and lethality. With respect to controls and single-drug treatments, the simultaneous administration of temporin L and β-lactams produced the highest antimicrobial activities and the strongest reduction in plasma endotoxin and TNF-α levels, resulting in the highest survival rates.

scholarly journals Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Amol T. Kothekar ◽  
Jigeeshu Vasishtha Divatia ◽  
Sheila Nainan Myatra ◽  
Anand Patil ◽  
Manjunath Nookala Krishnamurthy ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Modeling And Simulation ◽  
Empirical Therapy ◽  
Gram Negative Bacteria ◽  
Clinical Pharmacokinetics ◽  
Gram Negative ◽  
Arterial Blood ◽  
Days Of Therapy ◽  
Extended Infusion

Abstract Background Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40). We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock. We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100. Methods Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses. Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data. European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used. Results A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively. Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target. A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40. Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H). Conclusions In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires a bolus of 500 mg followed by EI of 1500 mg Q8H. While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.

Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria

2004 ◽  
Vol 69 (3) ◽  
pp. 778-784 ◽  
Author(s):  
Dusan Hesek ◽  
Maxim Suvorov ◽  
Ken-ichiro Morio ◽  
Mijoon Lee ◽  
Stephen Brown ◽  
...  
Keyword(s):  
Binding Protein ◽  
Gram Negative Bacteria ◽  
Penicillin Binding Protein ◽  
Gram Negative

scholarly journals Critical Role of Lipopolysaccharide-Binding Protein and CD14 in Immune Responses against Gram-Negative Bacteria

2001 ◽  
Vol 167 (5) ◽  
pp. 2759-2765 ◽  
Author(s):  
Didier Le Roy ◽  
Franco Di Padova ◽  
Yoshiyuki Adachi ◽  
Michel Pierre Glauser ◽  
Thierry Calandra ◽  
...  
Keyword(s):  
Immune Responses ◽  
Binding Protein ◽  
Critical Role ◽  
Gram Negative Bacteria ◽  
Lipopolysaccharide Binding Protein ◽  
Gram Negative ◽  
Lipopolysaccharide Binding

scholarly journals Polymyxin B Hemoperfusion in Pneumonic Septic Shock Caused by Gram-Negative Bacteria

2015 ◽  
Vol 30 (3) ◽  
pp. 171-175
Author(s):  
Jung-Wan Yoo ◽  
Su Yeon Park ◽  
Jin Jeon ◽  
Jin Won Huh ◽  
Chae-Man Lim ◽  
...  
Keyword(s):  
Septic Shock ◽  
Polymyxin B ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Polymyxin B Hemoperfusion

scholarly journals Phylogenomic insights into distribution and adaptation of Bdellovibrionota in marine waters

2020 ◽  
Author(s):  
Qing-Mei Li ◽  
Ying-Li Zhou ◽  
Zhan-Fei Wei ◽  
Yong Wang
Keyword(s):  
Comparative Genomics ◽  
Marine Environment ◽  
Deep Sea ◽  
Binding Protein ◽  
Glycerol Metabolism ◽  
Metabolic Reconstruction ◽  
Gram Negative Bacteria ◽  
Phylogenetic Groups ◽  
Gram Negative ◽  
Chitin Binding Protein

AbstractBdellovibrionota is composed of obligate predators that can consume some gram-negative bacteria inhabiting various environments. However, whether genomic traits influence their distribution and marine adaptation remains to be answered. In this study, we performed phylogenomics and comparative genomics studies on 82 Bdellovibrionota genomes along with five metagenome-assembled genomes (MAGs) from deep sea zones. Four phylogenetic groups, Oligoflexia, Bdello-group1, Bdello-group2 and Bacteriovoracia, were revealed by constructing a phylogenetic tree, of which 53.84% of Bdello-group2 and 48.94% of Bacteriovoracia were derived from ocean. Bacteriovoracia was more prevalent in deep sea zones, whereas Bdello-group2 was largely distributed in the epipelagic zone. Metabolic reconstruction indicated that genes involved in chemotaxis, flagellar (mobility), type II secretion system, ABC transporters and penicillin-binding protein were necessary for predatory lifestyle of Bdellovibrionota. Genes involved in glycerol metabolism, hydrogen peroxide (H2O2) degradation, cell wall recycling and peptide utilization were ubiquitously present in Bdellovibrionota genomes. Comparative genomics between marine and non-marine Bdellovibrionota demonstrated that betaine as an osmoprotectant is probably widely used by marine Bdellovibrionota, meanwhile, all the marine genomes have a number of related genes for adapting marine environment. The chitinase and chitin-binding protein encoding genes were identified for the first time in Oligoflexia, which implied that Oligoflexia may prey a wider spectrum of microbes. This study expanded our knowledge on adaption strategies of Bdellovibrionota inhabiting deep sea and their potential usage for biological control.ImportanceBdellovibrionota can prey gram-negative bacteria proposed as biocontrol agent. Available Bdellovibrionota genomes showed that most are from marine environment. However, vertical distribution and adaption of Bdellovibrionota in deep sea has not been reported. Our study of Bdellovibrionota revealed four groups (Oligoflexia, Bdello-group1, Bdello-group2 and Bacteriovoracia) and their distribution pattern in oceans. We also identified the genes for different phases of predation and adaptation in deep-sea environment. Moreover, Oligoflexia genomes contain more genes for carbohydrates utilization and particularly those encoding chitin-binding protein and chitinase. Our analyses of Bdellovibrionota genomes may help understand their special lifestyle and deep-sea adaptation.

scholarly journals Gram-negative trimeric porins have specific LPS binding sites that are essential for porin biogenesis

2016 ◽  
Vol 113 (34) ◽  
pp. E5034-E5043 ◽  
Author(s):  
Wanatchaporn Arunmanee ◽  
Monisha Pathania ◽  
Alexandra S. Solovyova ◽  
Anton P. Le Brun ◽  
Helen Ridley ◽  
...  
Keyword(s):  
Binding Sites ◽  
Calcium Ion ◽  
Gram Negative Bacteria ◽  
Core Oligosaccharide ◽  
Gram Negative ◽  
X Ray ◽  
Cross Links ◽  
Phosphate Groups ◽  
Positively Charged ◽  
Lps Binding

The outer membrane (OM) of gram-negative bacteria is an unusual asymmetric bilayer with an external monolayer of lipopolysaccharide (LPS) and an inner layer of phospholipids. The LPS layer is rigid and stabilized by divalent cation cross-links between phosphate groups on the core oligosaccharide regions. This means that the OM is robust and highly impermeable to toxins and antibiotics. During their biogenesis, OM proteins (OMPs), which function as transporters and receptors, must integrate into this ordered monolayer while preserving its impermeability. Here we reveal the specific interactions between the trimeric porins of Enterobacteriaceae and LPS. Isolated porins form complexes with variable numbers of LPS molecules, which are stabilized by calcium ions. In earlier studies, two high-affinity sites were predicted to contain groups of positively charged side chains. Mutation of these residues led to the loss of LPS binding and, in one site, also prevented trimerization of the porin, explaining the previously observed effect of LPS mutants on porin folding. The high-resolution X-ray crystal structure of a trimeric porin–LPS complex not only helps to explain the mutagenesis results but also reveals more complex, subtle porin–LPS interactions and a bridging calcium ion.

scholarly journals Bactericidal/permeability-increasing protein in the reproductive system of male mice may be involved in the sperm–oocyte fusion

Reproduction ◽  
2013 ◽  
Vol 146 (2) ◽  
pp. 135-144 ◽  
Author(s):  
Kun Li ◽  
Yue Liu ◽  
Xiaoyu Xia ◽  
Li Wang ◽  
Meige Lu ◽  
...  
Keyword(s):  
Transport Proteins ◽  
Seminal Vesicles ◽  
Lipid Transport ◽  
Human Neutrophils ◽  
Gram Negative Bacteria ◽  
Male Mice ◽  
Gram Negative ◽  
Major Function ◽  
The Family ◽  
Lps Binding

Bactericidal/permeability-increasing protein (BPI) is a 455-residue (∼55 kDa) protein found mainly in the primary (azurophilic) granules of human neutrophils. BPI is an endogenous antibiotic protein that belongs to the family of mammalian lipopolysaccharide (LPS)-binding and lipid transport proteins. Its major function is to kill Gram-negative bacteria, thereby protecting the host from infection. In addition, BPI can inhibit angiogenesis, suppress LPS-mediated platelet activation, increase DNA synthesis, and activate ERK/Akt signaling. In this study, we found thatBpiwas expressed in the testis and epididymis but not in the seminal vesicles, prostate, and solidification glands. BPI expression in the epididymis increased upon upregulation of testosterone, caused by injection of GNRH. In orchidectomized mice, BPI expression was significantly reduced, but its expression was restored to 30% of control levels in orchidectomized mice that received supplementary testosterone. The number of sperm fused per egg significantly decreased after incubation with anti-BPI antiserum. These results suggest that BPI may take part in the process of sperm–oocyte fusion and play a unique and significant role in reproduction.

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