scholarly journals CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Duan ◽  
Huikuan Chu ◽  
Katharina Brandl ◽  
Lu Jiang ◽  
Suling Zeng ◽  
...  
Keyword(s):  
Liver Disease ◽  
Enterococcus Faecalis ◽  
Hepatic Clearance ◽  
Immunoglobulin Superfamily ◽  
Wild Type ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Liver Macrophages ◽  
Related Liver Disease ◽  
Deficient Mice

AbstractComplement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg–Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease.

scholarly journals Characterization of Enterococcus faecalis Alkaline Phosphatase and Use in IdentifyingStreptococcus agalactiae Secreted Proteins

1999 ◽  
Vol 181 (18) ◽  
pp. 5790-5799 ◽  
Author(s):  
Martin H. Lee ◽  
Aphakorn Nittayajarn ◽  
R. Paul Ross ◽  
Cynthia B. Rothschild ◽  
Derek Parsonage ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Membrane Protein ◽  
Enterococcus Faecalis ◽  
Signal Sequence ◽  
Subcellular Location ◽  
Lactose Permease ◽  
Wild Type ◽  
Alkaline Phosphatases ◽  
Gram Positive ◽  
Gram Positive Bacteria

ABSTRACT We have identified and characterized an Enterococcus faecalis alkaline phosphatase (AP, encoded by phoZ). The predicted gene product shows homology with alkaline phosphatases from a variety of species; it has especially high similarity with two alkaline phosphatases from Bacillus subtilis. Expression ofphoZ in Escherichia coli, E. faecalis, Streptococcus agalactiae (group B streptococcus [GBS]), or Streptococcus pyogenes (group A streptococcus [GAS]) produces a blue-colony phenotype on plates containing a chromogenic substrate, 5-bromo-4-chloro-3-indolylphosphate (XP or BCIP). Two tests were made to determine if the activity of the enzyme is dependent upon the enzyme’s subcellular location. First, elimination of the signal sequence reduced AP activity to 3% of the wild-type activity (or less) in three species of gram-positive bacteria. Restoration of export, using the signal sequence from C5a peptidase, restored AP activity to at least 50% of that of the wild type. Second, we engineered two chimeric proteins in which AP was fused to either a periplasmic domain or a cytoplasmic domain of lactose permease (a membrane protein). In E. coli, the periplasmic fusion had 17-fold-higher AP activity than the cytoplasmic fusion. We concluded that AP activity is export dependent. The signal sequence deletion mutant, phoZΔss, was used to identify random genomic fragments from GBS that encode exported proteins or integral membrane proteins. Included in this set of fragments were genes that exhibited homology with the Rib protein (a cell wall protein from GBS) or with DppB (an integral membrane protein from GAS). AP acts as a reporter enzyme in GBS, GAS, and E. faecalis and is expected to be useful in a variety of gram-positive bacteria.

Influence of the cell wall on ciprofloxacin susceptibility in selected wild-type Gram-negative and Gram-positive bacteria

2004 ◽  
Vol 23 (6) ◽  
pp. 627-630 ◽  
Author(s):  
Mercedes Berlanga ◽  
M.Teresa Montero ◽  
Jordi Hernández-Borrell ◽  
Miquel Viñas
Keyword(s):  
Cell Wall ◽  
Wild Type ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Survival of some non-starter bacteria in naturally ripened and enzyme-accelerated Cheddar cheese

1988 ◽  
Vol 55 (4) ◽  
pp. 597-602 ◽  
Author(s):  
Lydia Bautista ◽  
Rohan G. Kroll
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Enterococcus Faecalis ◽  
Enzyme System ◽  
Cheddar Cheese ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Ripening Period ◽  
Gram Positive Bacteria

SummaryEffects of the addition of a proteinase (Neutrase 1–5S) and a peptidase (aminopeptidase DP-102) as agents for accelerating the ripening of Cheddar cheese on the survival of some non-starter bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coliand aSalmonellasp.) were studied throughout a 4-month ripening period. The enzymes were found to have no significant effect on the survival of the Gram-positive bacteria but some significant effects were observed, at some stages of the ripening period, with the Gram-negative bacteria in that lower levels were recovered from cheeses treated with the enzyme system.

scholarly journals Purification and Characterization of a Novel Bacteriocin Produced by Enterococcus faecalis Strain RJ-11

2003 ◽  
Vol 69 (10) ◽  
pp. 5746-5753 ◽  
Author(s):  
Yukio Yamamoto ◽  
Yoshikazu Togawa ◽  
Makoto Shimosaka ◽  
Mitsuo Okazaki
Keyword(s):  
Enterococcus Faecalis ◽  
Proteolytic Enzymes ◽  
Wide Spectrum ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Culture Fluid ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Heat Stable ◽  
Alkaline Conditions

ABSTRACT Lactic acid bacteria exhibiting activity against the gram-positive bacterium Bacillus subtilis were isolated from rice bran. One of the isolates, identified as Enterococcus faecalis RJ-11, exhibited a wide spectrum of growth inhibition with various gram-positive bacteria. A bacteriocin purified from culture fluid, designated enterocin RJ-11, was heat stable and was not sensitive to acid and alkaline conditions, but it was sensitive to several proteolytic enzymes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that enterocin RJ-11 had a molecular weight of 5,000 in its monomeric form. The amino acid sequence determined for purified enterocin RJ-11 exhibited high levels of similarity to the sequences of enterocins produced by Enterococcus faecium.

scholarly journals Inhibition of Methionyl-tRNA Synthetase by REP8839 and Effects of Resistance Mutations on Enzyme Activity

2008 ◽  
Vol 53 (1) ◽  
pp. 86-94 ◽  
Author(s):  
Louis S. Green ◽  
James M. Bullard ◽  
Wendy Ribble ◽  
Frank Dean ◽  
David F. Ayers ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanistic Explanation ◽  
Trna Synthetase ◽  
Turnover Rates ◽  
Wild Type ◽  
Resistance Mutations ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Human Orthologs ◽  
Methionyl Trna Synthetase

ABSTRACT REP8839 is a selective inhibitor of methionyl-tRNA synthetase (MetRS) with antibacterial activity against a variety of gram-positive organisms. We determined REP8839 potency against Staphylococcus aureus MetRS and assessed its selectivity for bacterial versus human orthologs of MetRS. The inhibition constant (Ki ) of REP8839 was 10 pM for Staphylococcus aureus MetRS. Inhibition of MetRS by REP8839 was competitive with methionine and uncompetitive with ATP. Thus, high physiological ATP levels would actually facilitate optimal binding of the inhibitor. While many gram-positive bacteria, such as Staphylococcus aureus, express exclusively the MetRS1 subtype, many gram-negative bacteria express an alternative homolog called MetRS2. Some gram-positive bacteria, such as Streptococcus pneumoniae and Bacillus anthracis, express both MetRS1 and MetRS2. MetRS2 orthologs were considerably less susceptible to REP8839 inhibition. REP8839 inhibition of human mitochondrial MetRS was 1,000-fold weaker than inhibition of Staphylococcus aureus MetRS; inhibition of human cytoplasmic MetRS was not detectable, corresponding to >1,000,000-fold selectivity for the bacterial target relative to its cytoplasmic counterpart. Mutations in MetRS that confer reduced susceptibility to REP8839 were examined. The mutant MetRS enzymes generally exhibited substantially impaired catalytic activity, particularly in aminoacylation turnover rates. REP8839 Ki values ranged from 4- to 190,000-fold higher for the mutant enzymes than for wild-type MetRS. These observations provide a potential mechanistic explanation for the reduced growth fitness observed with MetRS mutant strains relative to that with wild-type Staphylococcus aureus.

scholarly journals Enterococcus faecalis and pathogenic streptococciinactivate daptomycin by releasing phospholipids

2017 ◽  
Author(s):  
Elizabeth V. K. Ledger ◽  
Vera Pader ◽  
Andrew M. Edwards
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecalis ◽  
Staphylococcus Epidermidis ◽  
Defence Mechanism ◽  
Membrane Phospholipids ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Group A ◽  
Partial Inactivation ◽  
Lipopeptide Antibiotic

SummaryDaptomycin is a lipopeptide antibiotic with activity against Gram-positive bacteria. We have shown previously thatStaphylococcus aureuscan survive daptomycin exposure by releasing membrane phospholipids that inactivate the antibiotic. To determine whether other pathogens possess this defence mechanism, phospholipid release and daptomycin activity were measured after incubation ofStaphylococcus epidermidis, Group A or B streptococci,Streptococcus gordoniiorEnterococcus faecaliswith the antibiotic. All bacteria released phospholipid in response to daptomycin, which resulted in at least partial inactivation of the antibiotic. However,E. faecalisshowed the highest levels of lipid release and daptomycin inactivation. As shown previously forS. aureus, phospholipid release byE. faecaliswas inhibited by the lipid biosynthesis inhibitor platensimycin. In conclusion, several pathogenic Gram-positive bacteria, includingE. faecalis, inactivate daptomycin by releasing phospholipids, which may contribute to the failure of daptomycin to resolve infections caused by these pathogens.

scholarly journals NMR Hydrophilic Metabolomic Analysis of Bacterial Resistance Pathways using Multivalent Antimicrobials with Challenged and Unchallenged Wild Type and Mutated Gram-Positive Bacteria

2021 ◽  
Vol 22 (24) ◽  
pp. 13606
Author(s):  
Michelle L. Aries ◽  
Mary J. Cloninger
Keyword(s):  
Metabolic Pathways ◽  
Qualitative Method ◽  
Bacterial Resistance ◽  
Proton Nuclear Magnetic Resonance ◽  
Gram Negative Bacteria ◽  
Wild Type ◽  
Gram Positive ◽  
Resistance Development ◽  
Gram Positive Bacteria ◽  
Positively Charged

Multivalent membrane disruptors are a relatively new antimicrobial scaffold that are difficult for bacteria to develop resistance to and can act on both Gram-positive and Gram-negative bacteria. Proton Nuclear Magnetic Resonance (1H NMR) metabolomics is an important method for studying resistance development in bacteria, since this is both a quantitative and qualitative method to study and identify phenotypes by changes in metabolic pathways. In this project, the metabolic differences between wild type Bacillus cereus (B. cereus) samples and B. cereus that was mutated through 33 growth cycles in a nonlethal dose of a multivalent antimicrobial agent were identified. For additional comparison, samples for analysis of the wild type and mutated strains of B. cereus were prepared in both challenged and unchallenged conditions. A C16-DABCO (1,4‑diazabicyclo-2,2,2-octane) and mannose functionalized poly(amidoamine) dendrimer (DABCOMD) were used as the multivalent quaternary ammonium antimicrobial for this hydrophilic metabolic analysis. Overall, the study reported here indicates that B. cereus likely change their peptidoglycan layer to protect themselves from the highly positively charged DABCOMD. This membrane fortification most likely leads to the slow growth curve of the mutated, and especially the challenged mutant samples. The association of these sample types with metabolites associated with energy expenditure is attributed to the increased energy required for the membrane fortifications to occur as well as to the decreased diffusion of nutrients across the mutated membrane.

scholarly journals Apparent involvement of a multidrug transporter in the fluoroquinolone resistance of Streptococcus pneumoniae.

1997 ◽  
Vol 41 (6) ◽  
pp. 1396-1398 ◽  
Author(s):  
N N Baranova ◽  
A A Neyfakh
Keyword(s):  
Streptococcus Pneumoniae ◽  
Ethidium Bromide ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Multidrug Transporter ◽  
Wild Type ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Energy Dependent

A Streptococcus pneumoniae strain selected for resistance to ethidium bromide demonstrated enhanced energy-dependent efflux of this toxic dye. Both the ethidium resistance and the ethidium efflux could be inhibited by the plant alkaloid reserpine. The ethidium-selected cells demonstrated cross-resistance to the fluoroquinolones norfloxacin and ciprofloxacin; this resistance could also be completely reversed by reserpine. Furthermore, reserpine potentiated the susceptibility of wild-type S. pneumoniae to fluoroquinolones and ethidium. The most plausible explanation for these results is that S. pneumoniae, like some other gram-positive bacteria, expresses a reserpine-sensitive multidrug transporter, which may play an important role in both intrinsic and acquired resistances of this pathogen to fluoroquinolone therapy.

scholarly journals Alanyl-Phosphatidylglycerol and Lysyl-Phosphatidylglycerol Are Translocated by the Same MprF Flippases and Have Similar Capacities To Protect against the Antibiotic Daptomycin in Staphylococcus aureus

2012 ◽  
Vol 56 (7) ◽  
pp. 3492-3497 ◽  
Author(s):  
Christoph J. Slavetinsky ◽  
Andreas Peschel ◽  
Christoph M. Ernst
Keyword(s):  
Staphylococcus Aureus ◽  
Deletion Mutant ◽  
Wild Type ◽  
Gram Positive ◽  
Content Type ◽  
Wild Type Level ◽  
Bacterial Membranes ◽  
Gram Positive Bacteria ◽  
Cytoplasmic Membranes ◽  
Simultaneous Expression

ABSTRACTThe lysinylation of negatively charged phosphatidylglycerol by MprF proteins reduces the affinity of cationic antimicrobial peptides (CAMPs) for bacterial cytoplasmic membranes and reduces the susceptibility of several Gram-positive bacterial pathogens to CAMPs. MprF ofStaphylococcus aureusencompasses a lysyl-phosphatidylglycerol (Lys-PG) synthase and a Lys-PG flippase domain. In contrast,Clostridium perfringensencodes two MprF homologs which specifically synthesize alanyl-phosphatidylglycerol (Ala-PG) or Lys-PG, while only the Lys-PG synthase is fused to a putative flippase domain. It remains unknown whether cationic Lys-PG and zwitterionic Ala-PG differ in their capacities to be translocated by MprF flippases and if both can reduce CAMP susceptibility in Gram-positive bacteria. By expressing the MprF proteins ofC. perfringensin anS. aureus mprFdeletion mutant, we found that both lipids can be efficiently produced inS. aureus. Simultaneous expression of the Lys-PG and Ala-PG synthases led to the production of both lipids and slightly increased the overall amounts of aminoacyl phospholipids. Ala-PG production by the correspondingC. perfringensenzyme did not affect susceptibility to CAMPs such as nisin and gallidermin or to the CAMP-like antibiotic daptomycin. However, coexpression of the Ala-PG synthase with flippase domains of Lys-PG synthesizing MprF proteins led to a wild-type level of daptomycin susceptibility, indicating that Ala-PG can also protect bacterial membranes against daptomycin and suggesting that Lys-PG flippases can also translocate the related lipid Ala-PG. Thus, bacterial aminoacyl phospholipid flippases exhibit more relaxed substrate specificity and Ala-PG and Lys-PG are more similar in their capacities to modulate membrane functions than anticipated.

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