Glucosylceramide Changes Bacterial Metabolism and Increases Gram-Positive Bacteria through Tolerance to Secondary Bile Acids In Vitro.
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ABSTRACT:
SUBMITTER: Dai H
PROVIDER: S-EPMC9141989 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity--the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid--against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. D-sphingosine (MBC range, 0.3 to 19.6 μg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 μg/ml), and phytosphingosine (MBC range, 3.3 to 62.5 μg/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.
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Project description:The spread of microorganisms causing health-care associated infection (HAI) is contributed to by their intrinsic tolerance to a variety of biocides, used as antiseptics or disinfectants. The natural monomeric stilbenoid resveratrol (RV) is able to modulate the susceptibility to the chlorhexidine digluconate (CHX) biocide in Acinetobacter baumannii. In this study, a panel of reference strains and clinical isolates of Gram-negative bacteria, Gram-positive bacteria and yeasts were analyzed for susceptibility to CHX and benzalkonium chloride (BZK) and found to be tolerant to one or both biocides. The carbonyl cyanide m-chlorophenylhydrazine protonophore (CCCP) efflux pump inhibitor reduced the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CHX and BZK in the majority of strains. RV reduced dose-dependently MIC and MBC of CHX and BZK biocides when used as single agents or in combination in all analyzed strains, but not CHX MIC and MBC in Pseudomonas aeruginosa, Candida albicans, Klebsiella pneumoniae, Stenotrophomonas maltophilia and Burkholderia spp. strains. In conclusion, RV reverts tolerance and restores susceptibility to CHX and BZK in the majority of microorganisms responsible for HAI. These results indicates that the combination of RV, CHX and BZK may represent a useful strategy to maintain susceptibility to biocides in several nosocomial pathogens.
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Project description:Lipoteichoic acids (LTA) are polymers of alternating units of a polyhydroxy alkane, including glycerol and ribitol, and phosphoric acid, joined to form phosphodiester units that are found in the envelope of Gram-positive bacteria. Here we review four different types of LTA that can be distinguished on the basis of their chemical structure and describe recent advances in the biosynthesis pathway for type I LTA, d-alanylated polyglycerol-phosphate linked to di-glucosyl-diacylglycerol. The physiological functions of type I LTA are discussed in the context of inhibitors that block their synthesis and of mutants with discrete synthesis defects. Research on LTA structure and function represents a large frontier that has been investigated in only few Gram-positive bacteria.
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Project description:BackgroundThe histidine metabolism and transport (his) genes are controlled by a variety of RNA-dependent regulatory systems among diverse taxonomic groups of bacteria including T-box riboswitches in Firmicutes and Actinobacteria and RNA attenuators in Proteobacteria. Using a comparative genomic approach, we previously identified a novel DNA-binding transcription factor (named HisR) that controls the histidine metabolism genes in diverse Gram-positive bacteria from the Firmicutes phylum.ResultsHere we report the identification of HisR-binding sites within the regulatory regions of the histidine metabolism and transport genes in 395 genomes representing the Bacilli, Clostridia, Negativicutes, and Tissierellia classes of Firmicutes, as well as in 97 other HisR-encoding genomes from the Actinobacteria, Proteobacteria, and Synergistetes phyla. HisR belongs to the TrpR family of transcription factors, and their predicted DNA binding motifs have a similar 20-bp palindromic structure but distinct lineage-specific consensus sequences. The predicted HisR-binding motif was validated in vitro using DNA binding assays with purified protein from the human gut bacterium Ruminococcus gnavus. To fill a knowledge gap in the regulation of histidine metabolism genes in Firmicutes genomes that lack a hisR repressor gene, we systematically searched their upstream regions for potential RNA regulatory elements. As result, we identified 158 T-box riboswitches preceding the histidine biosynthesis and/or transport genes in 129 Firmicutes genomes. Finally, novel candidate RNA attenuators were identified upstream of the histidine biosynthesis operons in six species from the Bacillus cereus group, as well as in five Eubacteriales and six Erysipelotrichales species.ConclusionsThe obtained distribution of the HisR transcription factor and two RNA-mediated regulatory mechanisms for histidine metabolism genes across over 600 species of Firmicutes is discussed from functional and evolutionary points of view.
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Project description:Clostridium scindens biotransforms primary bile acids into secondary bile acids, and is correlated with inhibition of Clostridium difficile growth in vivo. The aim of the current study was to determine how C. scindens regulates C. difficile growth in vitro and if these interactions might relate to the regulation of gut microbiome structure in vivo. The bile acid 7?-dehydroxylating gut bacteria, C. scindens and C. sordellii, were found to secrete the tryptophan-derived antibiotics, 1-acetyl-?-carboline and turbomycin A, respectively. Both antibiotics inhibited growth of C. difficile and other gut bacteria. The secondary bile acids, deoxycholic acid and lithocholic acid, but not cholic acid, enhanced the inhibitory activity of these antibiotics. These antibiotics appear to inhibit cell division of C. difficile. The results help explain how endogenously synthesized antibiotics and secondary bile acids may regulate C. difficile growth and the structure of the gut microbiome in health and disease.
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Project description:Secondary bacterial pneumonias are a frequent complication of influenza and other respiratory viral infections, but the mechanisms underlying viral-induced susceptibility to bacterial infections are poorly understood. In particular, it is unclear whether the host's response against the viral infection, independent of the injury caused by the virus, results in impairment of antibacterial host defense. Here, we sought to determine whether the induction of an "antiviral" immune state using various viral recognition receptor ligands was sufficient to result in decreased ability to combat common bacterial pathogens of the lung. Using a mouse model, animals were administered polyinosine-polycytidylic acid (poly I:C) or Toll-like 7 ligand (imiquimod or gardiquimod) intranasally, followed by intratracheal challenge with Streptococcus pneumoniae. We found that animals pre-exposed to poly I:C displayed impaired bacterial clearance and increased mortality. Poly I:C-exposed animals also had decreased ability to clear methicillin-resistant Staphylococcus aureus. Furthermore, we showed that activation of Toll-like receptor (TLR)3 and Retinoic acid inducible gene (RIG-I)/Cardif pathways, which recognize viral nucleic acids in the form of dsRNA, both contribute to poly I:C mediated impairment of bacterial clearance. Finally, we determined that poly I:C administration resulted in significant induction of type I interferons (IFNs), whereas the elimination of type I IFN signaling improved clearance and survival following secondary bacterial pneumonia. Collectively, these results indicate that in the lung, poly I:C administration is sufficient to impair pulmonary host defense against clinically important gram-positive bacterial pathogens, which appears to be mediated by type I IFNs.
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Project description:We have conjugated dodecyl and octadecyl fatty acids to the N-terminus of SC4, a potently bactericidal, helix-forming peptide 12-mer (KLFKRHLKWKII), and examined the bactericidal activities of the resultant SC4 'peptide-amphiphile' molecules. SC4 peptide-amphiphiles showed up to a 30-fold increase in bactericidal activity against Gram-positive strains (Staphylococcus aureus, Streptococcus pyogenes and Bacillus anthracis), including S. aureus strains resistant to conventional antibiotics, but little or no increase in bactericidal activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fatty acid conjugation improved endotoxin (lipopolysaccharide) neutralization by 3- to 6-fold. Although acylation somewhat increased lysis of human erythrocytes, it did not increase lysis of endothelial cells, and the haemolytic effects occurred at concentrations 10- to 100-fold higher than those required for bacterial cell lysis. For insight into the mechanism of action of SC4 peptide-amphiphiles, CD, NMR and fluorescence spectroscopy studies were performed in micelle and liposome models of eukaryotic and bacterial cell membranes. CD indicated that SC4 peptide-amphiphiles had the strongest helical tendencies in liposomes mimicking bacterial membranes, and strong membrane integration of the SC4 peptide-amphiphiles was observed using tryptophan fluorescence spectroscopy under these conditions; results that correlated with the increased bactericidal activities of SC4 peptide-amphiphiles. NMR structural analysis in micelles demonstrated that the two-thirds of the peptide closest to the fatty acid tail exhibited a helical conformation, with the positively-charged side of the amphipathic helix interacting more with the model membrane surface. These results indicate that conjugation of a fatty acid chain to the SC4 peptide enhances membrane interactions, stabilizes helical structure in the membrane-bound state and increases bactericidal potency.
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Project description:Signal intensities of BC-GP array for 105 speimens The Verigene Gram-Positive Blood Culture (BC-GP) nucleic acid assay is an automated microarray-based test, which can detect 12 Gram-positive bacterial genes and 3 resistance determinants using blood culture broths. We investigated signal intensities of microarray spots, and reclassified undetermined results where the automated system failed and various errors were called in blood culture specimens and spiked samples.
2014-05-30 | GSE57245 | GEO
Project description:In Gram-positive bacteria proteins are displayed on the cell surface using sortase enzymes. These cysteine transpeptidases join proteins bearing an appropriate sorting signal to strategically positioned amino groups on the cell surface. Working alone, or in concert with other enzymes, sortases either attach proteins to the cross-bridge peptide of the cell wall or they link proteins together to form pili. Because surface proteins play a fundamental role in microbial physiology and are frequently virulence factors, sortase enzymes have been intensely studied since their discovery a little more than a decade ago. Based on their primary sequences and functions sortases can be partitioned into distinct families called class A to F enzymes. Most bacteria elaborate their surfaces using more than one type of sortase that function non-redundantly by recognizing unique sorting signals within their protein substrates. Here we review what is known about the functions of these enzymes and the molecular basis of catalysis. Particular emphasis is placed on 'pilin' specific class C sortases that construct structurally complex pili. Exciting new data have revealed that these enzymes are amazingly promiscuous in the substrates that they can employ and that there is a startling degree of diversity in their mechanism of action. We also review recent data that suggest that sortases are targeted to specific sites on the cell surface where they work with other sortases and accessory factors to properly function.
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Project description:Signal intensities of BC-GP array for 105 speimens The Verigene Gram-Positive Blood Culture (BC-GP) nucleic acid assay is an automated microarray-based test, which can detect 12 Gram-positive bacterial genes and 3 resistance determinants using blood culture broths. We investigated signal intensities of microarray spots, and reclassified undetermined results where the automated system failed and various errors were called in blood culture specimens and spiked samples. Signal intensity analysis of BC-GP assay. SAMPLE_077 [Blood culture, Escherichia coli, Gram-negative, BacTALERT, Supernatant, Peripheral blood] had no signal data in the array raw data. Thus, SAMPLE_077 is not represented in this Series.
2014-05-30 | E-GEOD-57245 | biostudies-arrayexpress