scholarly journals Phosphatidylcholine Biosynthesis in Mitis Group Streptococci via Host Metabolite Scavenging

2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Luke R. Joyce ◽  
Ziqiang Guan ◽  
Kelli L. Palmer
Keyword(s):  
Membrane Lipids ◽  
Cellular Membrane ◽  
Human Pathogen ◽  
Content Type ◽  
Membrane Biology ◽  
Host Interactions ◽  
Fundamental Information ◽  
Phosphatidylcholine Biosynthesis ◽  
Health And Disease ◽  
Mechanistic Basis

ABSTRACT The mitis group streptococci include the major human pathogen Streptococcus pneumoniae and the opportunistic pathogens Streptococcus mitis and Streptococcus oralis, which are human oral cavity colonizers and agents of bacteremia and infective endocarditis in immunocompromised patients. Bacterial membrane lipids play crucial roles in microbe-host interactions; for many pathogens, however, the composition of the membrane is poorly understood. In this study, we characterized the lipidomes of selected species of mitis group streptococci and investigated the mechanistic basis for biosynthesis of the phospholipid phosphatidylcholine (PC). PC is a major lipid in eukaryotic cellular membranes, but it is considered to be comparatively rare in bacterial taxa. Using liquid chromatography-mass spectrometry in conjunction with stable isotope tracing, we determined that mitis group streptococci synthesize PC via a rare host-metabolite-scavenging pathway, the glycerophosphocholine (GPC) pathway, which is largely uncharacterized in bacteria. Our work demonstrates that mitis group streptococci, including S. pneumoniae, remodel their membranes in response to the major human metabolites GPC and lysophosphatidylcholine. IMPORTANCE We lack fundamental information about the composition of the cellular membrane even for the best-studied pathogens of critical significance for human health. The mitis group streptococci are closely linked to humans in health and disease, but their membrane biology is poorly understood. Here, we demonstrate that these streptococci scavenge major human metabolites and use them to synthesize the membrane phospholipid PC. Our work is significant because it identifies a mechanism by which the major human pathogen S. pneumoniae and the primary human oral colonizers S. mitis and S. oralis remodel their membranes in response to host metabolites.

scholarly journals Phosphatidylcholine biosynthesis in Mitis group streptococci via host metabolite scavenging

2019 ◽  
Author(s):  
Luke R. Joyce ◽  
Ziqiang Guan ◽  
Kelli L. Palmer
Keyword(s):  
Membrane Lipids ◽  
Cellular Membrane ◽  
Human Pathogen ◽  
Opportunistic Pathogens ◽  
Membrane Biology ◽  
Host Interactions ◽  
Fundamental Information ◽  
Phosphatidylcholine Biosynthesis ◽  
Health And Disease ◽  
Mechanistic Basis

AbstractThe Mitis group streptococci include the major human pathogenStreptococcus pneumoniaeand the opportunistic pathogensS. mitisandS. oraliswhich are human oral cavity colonizers and agents of bacteremia and infective endocarditis in immunocompromised patients. Bacterial membrane lipids play crucial roles in microbe-host interactions, yet for many pathogens, the composition of the membrane is poorly understood. In this study, we characterized the lipidomes of selected species of Mitis group streptococci and investigated the mechanistic basis for biosynthesis of the phospholipid phosphatidylcholine (PC). PC is a major lipid in eukaryotic cellular membranes, but it is considered to be comparatively rare in bacterial taxa. Using liquid chromatography/mass spectrometry (LC/MS) in conjunction with stable isotope tracing, we determined that Mitis group streptococci synthesize PC via the rare host metabolite scavenging pathway, the glycerophosphocholine (GPC) pathway, which is largely uncharacterized in bacteria. Our work demonstrates that Mitis group streptococci includingS. pneumoniaeremodel their membrane in response to the major human metabolites GPC and lysoPC.ImportanceWe lack fundamental information about the composition of the cellular membrane even for the best studied pathogens of critical significance for human health. The Mitis group streptococci are closely linked to humans in health and disease, yet their membrane biology is poorly understood. Here, we demonstrate that these streptococci scavenge major human metabolites and use them to synthesize the membrane phospholipid phosphatidylcholine. Our work is significant because it identifies a mechanism by which the major human pathogenS. pneumoniaeand the primary human oral colonizersS. mitisandS. oralisremodel their membrane in response to host metabolites.

scholarly journals The Glycine Lipids ofBacteroides thetaiotaomicronAre Important for Fitness during GrowthIn VivoandIn Vitro

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Alli Lynch ◽  
Seshu R. Tammireddy ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
David J. Clarke
Keyword(s):  
Amino Acid ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Cellular Membrane ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Acyltransferase Activity ◽  
Content Type ◽  
Health And Disease ◽  
And Function

ABSTRACTAcylated amino acids function as important components of the cellular membrane in some bacteria. Biosynthesis is initiated by theN-acylation of the amino acid, and this is followed by subsequentO-acylation of the acylated molecule, resulting in the production of the mature diacylated amino acid lipid. In this study, we use both genetics and liquid chromatography-mass spectrometry (LC-MS) to characterize the biosynthesis and function of a diacylated glycine lipid (GL) species produced inBacteroides thetaiotaomicron. We, and others, have previously reported the identification of a gene, namedglsBin this study, that encodes anN-acyltransferase activity responsible for the production of a monoacylated glycine calledN-acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of theBacteroidalesgenomes sequenced so far, theglsBgene is located immediately downstream from a gene, namedglsA, that is also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that the coexpression ofglsBandglsAresults in the production of GL inEscherichia coli. We constructed a deletion mutant of theglsBgene inB. thetaiotaomicron, and we confirm thatglsBis required for the production of GL inB. thetaiotaomicron. Moreover, we show thatglsBis important for the ability ofB. thetaiotaomicronto adapt to stress and colonize the mammalian gut. Therefore, this report describes the genetic requirements for the biosynthesis of GL, a diacylated amino acid species that contributes to fitness in the human gut bacteriumB. thetaiotaomicron.IMPORTANCEThe gut microbiome has an important role in both health and disease of the host. The mammalian gut microbiome is often dominated by bacteria from theBacteroidales, an order that includesBacteroidesandPrevotella. In this study, we have identified an acylated amino acid, called glycine lipid, produced byBacteroides thetaiotaomicron, a beneficial bacterium originally isolated from the human gut. In addition to identifying the genes required for the production of glycine lipids, we show that glycine lipids have an important role during the adaptation ofB. thetaiotaomicronto a number of environmental stresses, including exposure to either bile or air. We also show that glycine lipids are important for the normal colonization of the murine gut byB. thetaiotaomicron. This work identifies glycine lipids as an important fitness determinant inB. thetaiotaomicronand therefore increases our understanding of the molecular mechanisms underpinning colonization of the mammalian gut by beneficial bacteria.

The organization of cell surface membrane domains

1989 ◽  
Vol 47 ◽  
pp. 804-805
Author(s):  
Michael Edidin
Keyword(s):  
Cell Surface ◽  
Membrane Lipids ◽  
Surface Membrane ◽  
Lateral Diffusion ◽  
Cell Types ◽  
Membrane Domains ◽  
Membrane Biology ◽  
Morphological Polarity ◽  
Discrete Domains ◽  
Membrane Components

Cell surface membranes are based on a fluid lipid bilayer and models of the membranes' organization have emphasised the possibilities for lateral motion of membrane lipids and proteins within the bilayer. Two recent trends in cell and membrane biology make us consider ways in which membrane organization works against its inherent fluidity, localizing both lipids and proteins into discrete domains. There is evidence for such domains, even in cells without obvious morphological polarity and organization [Table 1]. Cells that are morphologically polarised, for example epithelial cells, raise the issue of membrane domains in an accute form.The technique of fluorescence photobleaching and recovery, FPR, was developed to measure lateral diffusion of membrane components. It has also proven to be a powerful tool for the analysis of constraints to lateral mobility. FPR resolves several sorts of membrane domains, all on the micrometer scale, in several different cell types.

scholarly journals Melanization in Cryptococcus neoformans Requires Complex Regulation

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Radames J. B. Cordero ◽  
Emma Camacho ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Defense Mechanisms ◽  
Environmental Stressors ◽  
Antimicrobial Compounds ◽  
Human Pathogen ◽  
Content Type ◽  
Signaling Mechanisms ◽  
Complex Regulation ◽  
Multiple Levels ◽  
Melanin Binding

ABSTRACT The fungal human pathogen Cryptococcus neoformans undergoes melanization in response to nutrient starvation and exposure to exogenous melanin precursors. Melanization protects the fungus against host defense mechanisms such as oxidative damage and other environmental stressors (e.g., heat/cold stress, antimicrobial compounds, ionizing radiation). Conversely, the melanization process generates cytotoxic intermediates, and melanized cells are potentially susceptible to overheating and to certain melanin-binding drugs. Despite the importance of melanin in C. neoformans biology, the signaling mechanisms regulating its synthesis are poorly understood. The recent report by D. Lee, E.-H. Jang, M. Lee, S.-W. Kim, et al. [mBio 10(5):e02267-19, 2019, https://doi.org/10.1128/mBio.02267-19] provides new insights into how C. neoformans regulates melanization. The authors identified a core melanin regulatory network consisting of transcription factors and kinases required for melanization under low-nutrient conditions. The redundant and epistatic connections of this melanin-regulating network demonstrate that C. neoformans melanization is complex and carefully regulated at multiple levels. Such complex regulation reflects the multiple functions of melanin in C. neoformans biology.

scholarly journals Complete Genome Sequence of Stenotrophomonas Phage Mendera

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Kameron D. Garza ◽  
Heather Newkirk ◽  
Russell Moreland ◽  
Carlos F. Gonzalez ◽  
Mei Liu ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Stenotrophomonas Maltophilia ◽  
Human Pathogen ◽  
Base Pairs ◽  
Content Type ◽  
Genomic Annotation ◽  
Opportunistic Human Pathogen

Stenotrophomonas maltophilia is an emerging opportunistic human pathogen. In this report, we describe the isolation and genomic annotation of the S. maltophilia-infecting bacteriophage Mendera. A myophage of 159,961 base pairs, Mendera is T4-like and related most closely to Stenotrophomonas phage IME-SM1.

scholarly journals Masking of β(1-3)-Glucan in the Cell Wall of Candida albicans from Detection by Innate Immune Cells Depends on Phosphatidylserine

2014 ◽  
Vol 82 (10) ◽  
pp. 4405-4413 ◽  
Author(s):  
Sarah E. Davis ◽  
Alex Hopke ◽  
Steven C. Minkin ◽  
Anthony E. Montedonico ◽  
Robert T. Wheeler ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
De Novo ◽  
Invasive Disease ◽  
Innate Immune ◽  
Dependent Manner ◽  
Content Type ◽  
Immune Effector ◽  
Host Interactions ◽  
Innate Immune Effector

ABSTRACTThe virulence ofCandida albicansin a mouse model of invasive candidiasis is dependent on the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE). Disruption of the PS synthase geneCHO1(i.e.,cho1Δ/Δ) eliminates PS and blocks thede novopathway for PE biosynthesis. In addition, thecho1Δ/Δ mutant's ability to cause invasive disease is severely compromised. Thecho1Δ/Δ mutant also exhibits cell wall defects, and in this study, it was determined that loss of PS results in decreased masking of cell wall β(1-3)-glucan from the immune system. In wild-typeC. albicans, the outer mannan layer of the wall masks the inner layer of β(1-3)-glucan from exposure and detection by innate immune effector molecules like the C-type signaling lectin Dectin-1, which is found on macrophages, neutrophils, and dendritic cells. Thecho1Δ/Δ mutant exhibits increases in exposure of β(1-3)-glucan, which leads to greater binding by Dectin-1 in both yeast and hyphal forms. The unmasking of β(1-3)-glucan also results in increased elicitation of TNF-α from macrophages in a Dectin-1-dependent manner. The role of phospholipids in fungal pathogenesis is an emerging field, and this is the first study showing that loss of PS inC. albicansresults in decreased masking of β(1-3)-glucan, which may contribute to our understanding of fungus-host interactions.

scholarly journals A Prospective Study of Acinetobacter baumannii Complex Isolates and Colistin Susceptibility Monitoring by Mass Spectrometry of Microbial Membrane Glycolipids

2018 ◽  
Vol 57 (3) ◽  
Author(s):  
Lisa M. Leung ◽  
Christi L. McElheny ◽  
Francesca M. Gardner ◽  
Courtney E. Chandler ◽  
Sarah L. Bowler ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Acinetobacter Baumannii ◽  
Lipid A ◽  
Membrane Lipids ◽  
Clinical Isolates ◽  
Colistin Resistance ◽  
Hospital System ◽  
Content Type ◽  
Acinetobacter Baumannii Complex ◽  
Gram Negative Organisms

ABSTRACT Acinetobacter baumannii is a prevalent nosocomial pathogen with a high incidence of multidrug resistance. Treatment of infections due to this organism with colistin, a last-resort antibiotic of the polymyxin class, can result in the emergence of colistin-resistant strains. Colistin resistance primarily occurs via modifications of the terminal phosphate moieties of lipopolysaccharide-derived lipid A, which reduces overall membrane electronegativity. These modifications are readily identified by mass spectrometry (MS). In this study, we prospectively collected Acinetobacter baumannii complex clinical isolates from a hospital system in Pennsylvania over a 3-year period. All isolates were evaluated for colistin resistance using standard MIC testing by both agar dilution and broth microdilution, as well as genospecies identification and lipid A profiling using MS analyses. Overall, an excellent correlation between colistin susceptibility and resistance, determined by MIC testing, and the presence of a lipid A modification, determined by MS, was observed with a sensitivity of 92.9% and a specificity of 94.0%. Additionally, glycolipid profiling was able to differentiate A. baumannii complex organisms based on their membrane lipids. With the growth of MS use in clinical laboratories, a reliable MS-based glycolipid phenotyping method that identifies colistin resistance in A. baumannii complex clinical isolates, as well as other Gram-negative organisms, represents an alternative or complementary approach to existing diagnostics.

scholarly journals Serum Albumin and Ca2+Are Natural Competence Inducers in the Human Pathogen Acinetobacter baumannii

2016 ◽  
Vol 60 (8) ◽  
pp. 4920-4929 ◽  
Author(s):  
German Matias Traglia ◽  
Brettni Quinn ◽  
Sareda T. J. Schramm ◽  
Alfonso Soler-Bistue ◽  
Maria Soledad Ramirez
Keyword(s):  
Acinetobacter Baumannii ◽  
Natural Transformation ◽  
Hospital Environment ◽  
Human Pathogen ◽  
Nosocomial Pathogen ◽  
Natural Competence ◽  
Exogenous Dna ◽  
Content Type ◽  
Resistance Determinants ◽  
Main Protein

ABSTRACTThe increasing frequency of bacteria showing antimicrobial resistance (AMR) raises the menace of entering into a postantibiotic era. Horizontal gene transfer (HGT) is one of the prime reasons for AMR acquisition.Acinetobacter baumanniiis a nosocomial pathogen with outstanding abilities to survive in the hospital environment and to acquire resistance determinants. Its capacity to incorporate exogenous DNA is a major source of AMR genes; however, few studies have addressed this subject. The transformation machinery as well as the factors that induce natural competence inA. baumanniiare unknown. In this study, we demonstrate that naturally competent strain A118 increases its natural transformation frequency upon the addition of Ca2+or albumin. We show thatcomEAandpilQare involved in this process since their expression levels are increased upon the addition of these compounds. An unspecific protein, like casein, does not reproduce this effect, showing that albumin's effect is specific. Our work describes the first specific inducers of natural competence inA. baumannii. Overall, our results suggest that the main protein in blood enhances HGT inA. baumannii, contributing to the increase of AMR in this threatening human pathogen.

scholarly journals Bacteriophages LIMElight and LIMEzero of Pantoea agglomerans, Belonging to the “phiKMV-Like Viruses”

2011 ◽  
Vol 77 (10) ◽  
pp. 3443-3450 ◽  
Author(s):  
Evelien M. Adriaenssens ◽  
Pieter-Jan Ceyssens ◽  
Vincent Dunon ◽  
Hans-Wolfgang Ackermann ◽  
Johan Van Vaerenbergh ◽  
...  
Keyword(s):  
Soil Samples ◽  
Pantoea Agglomerans ◽  
Open Reading Frames ◽  
Human Pathogen ◽  
Content Type ◽  
Host Diversity ◽  
Double Stranded Dna ◽  
Opportunistic Human Pathogen ◽  
Reading Frames

ABSTRACTPantoea agglomeransis a common soil bacterium used in the biocontrol of fungi and bacteria but is also an opportunistic human pathogen. It has been described extensively in this context, but knowledge of bacteriophages infecting this species is limited. Bacteriophages LIMEzero and LIMElight ofP. agglomeransare lytic phages, isolated from soil samples, belonging to thePodoviridaeand are the firstPantoeaphages of this family to be described. The double-stranded DNA (dsDNA) genomes (43,032 bp and 44,546 bp, respectively) encode 57 and 55 open reading frames (ORFs). Based on the presence of an RNA polymerase in their genomes and their overall genome architecture, these phages should be classified in the subfamily of theAutographivirinae, within the genus of the “phiKMV-like viruses.” Phylogenetic analysis of all the sequenced members of theAutographivirinaesupports the classification of phages LIMElight and LIMEzero as members of the “phiKMV-like viruses” and corroborates the subdivision into the different genera. These data expand the knowledge ofPantoeaphages and illustrate the wide host diversity of phages within the “phiKMV-like viruses.”

scholarly journals Function of the CRISPR-Cas System of the Human Pathogen Clostridium difficile

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Pierre Boudry ◽  
Ekaterina Semenova ◽  
Marc Monot ◽  
Kirill A. Datsenko ◽  
Anna Lopatina ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Type I ◽  
Human Pathogen ◽  
Range Analysis ◽  
Data Set ◽  
Content Type ◽  
Crispr System ◽  
Nosocomial Diarrhea ◽  
Active Expression ◽  
Foreign Dna

ABSTRACT Clostridium difficile is the cause of most frequently occurring nosocomial diarrhea worldwide. As an enteropathogen, C. difficile must be exposed to multiple exogenous genetic elements in bacteriophage-rich gut communities. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems allow bacteria to adapt to foreign genetic invaders. Our recent data revealed active expression and processing of CRISPR RNAs from multiple type I-B CRISPR arrays in C. difficile reference strain 630. Here, we demonstrate active expression of CRISPR arrays in strain R20291, an epidemic C. difficile strain. Through genome sequencing and host range analysis of several new C. difficile phages and plasmid conjugation experiments, we provide evidence of defensive function of the CRISPR-Cas system in both C. difficile strains. We further demonstrate that C. difficile Cas proteins are capable of interference in a heterologous host, Escherichia coli. These data set the stage for mechanistic and physiological analyses of CRISPR-Cas-mediated interactions of important global human pathogen with its genetic parasites. IMPORTANCE Clostridium difficile is the major cause of nosocomial infections associated with antibiotic therapy worldwide. To survive in bacteriophage-rich gut communities, enteropathogens must develop efficient systems for defense against foreign DNA elements. CRISPR-Cas systems have recently taken center stage among various anti-invader bacterial defense systems. We provide experimental evidence for the function of the C. difficile CRISPR system against plasmid DNA and bacteriophages. These data demonstrate the original features of active C. difficile CRISPR system and bring important insights into the interactions of this major enteropathogen with foreign DNA invaders during its infection cycle.

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