scholarly journals Sialic acid acquisition in bacteria–one substrate, many transporters

2016 ◽  
Vol 44 (3) ◽  
pp. 760-765 ◽  
Author(s):  
Gavin H. Thomas
Keyword(s):  
Sialic Acid ◽  
Immune Evasion ◽  
Sialic Acids ◽  
Major Facilitator Superfamily ◽  
Acid Uptake ◽  
Gram Negative Bacteria ◽  
Acetylneuraminic Acid ◽  
Wide Range ◽  
Major Facilitator

The sialic acids are a family of 9-carbon sugar acids found predominantly on the cell-surface glycans of humans and other animals within the Deuterostomes and are also used in the biology of a wide range of bacteria that often live in association with these animals. For many bacteria sialic acids are simply a convenient source of food, whereas for some pathogens they are also used in immune evasion strategies. Many bacteria that use sialic acids derive them from the environment and so are dependent on sialic acid uptake. In this mini-review I will describe the discovery and characterization of bacterial sialic acids transporters, revealing that they have evolved multiple times across multiple diverse families of transporters, including the ATP-binding cassette (ABC), tripartite ATP-independent periplasmic (TRAP), major facilitator superfamily (MFS) and sodium solute symporter (SSS) transporter families. In addition there is evidence for protein-mediated transport of sialic acids across the outer membrane of Gram negative bacteria, which can be coupled to periplasmic processing of different sialic acids to the most common form, β-D-N-acetylneuraminic acid (Neu5Ac) that is most frequently taken up into the cell.

scholarly journals NontypeableHaemophilus influenzaeHas Evolved Preferential Use ofN-Acetylneuraminic Acid as a Host Adaptation

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Preston S. K. Ng ◽  
Christopher J. Day ◽  
John M. Atack ◽  
Lauren E. Hartley-Tassell ◽  
Linda E. Winter ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antibody Response ◽  
Immune Evasion ◽  
Biofilm Formation ◽  
Culture Media ◽  
Carbon Sources ◽  
Bacterial Pathogen ◽  
Catalytic Efficiency ◽  
Human Antibody ◽  
Acetylneuraminic Acid

ABSTRACTNontypeableHaemophilus influenzae(NTHi) is a Gram-negative bacterial pathogen that is adapted exclusively to human hosts. NTHi utilizes sialic acid from the host as a carbon source and as a terminal sugar on the outer membrane glycolipid lipooligosaccharide (LOS). Sialic acid expressed on LOS is critical in NTHi biofilm formation and immune evasion. There are two major forms of sialic acids in most mammals,N-acetylneuraminic acid (Neu5Ac) andN-glycolylneuraminic acid (Neu5Gc), the latter of which is derived from Neu5Ac. Humans lack the enzyme to convert Neu5Ac to Neu5Gc and do not express Neu5Gc in normal tissues; instead, Neu5Gc is recognized as a foreign antigen. A recent study showed that dietary Neu5Gc can be acquired by NTHi colonizing humans and then presented on LOS, which acts as an antigen for the initial induction of anti-Neu5Gc antibodies. Here we examined Neu5Gc uptake and presentation on NTHi LOS. We show that, although Neu5Gc and Neu5Ac are utilized equally well as sole carbon sources, Neu5Gc is not incorporated efficiently into LOS. When equal amounts of Neu5Gc and Neu5Ac are provided in culture media, there is ∼4-fold more Neu5Ac incorporated into LOS, suggesting a bias in a step of the LOS biosynthetic pathway. CMP-Neu5Ac synthetase (SiaB) was shown to have ∼4,000-fold-higher catalytic efficiency for Neu5Ac than for Neu5Gc. These data suggest that NTHi has adapted preferential utilization of Neu5Ac, thus avoiding presentation of the nonhuman Neu5Gc in the bacterial cell surface. The selective pressure for this adaptation may represent the human antibody response to the Neu5Gc xenoantigen.IMPORTANCEHost-adapted bacterial pathogens such as NTHi cannot survive out of their host environment and have evolved host-specific mechanisms to obtain nutrients and evade the immune response. Relatively few of these host adaptations have been characterized at the molecular level. NTHi utilizes sialic acid as a nutrient and also incorporates this sugar into LOS, which is important in biofilm formation and immune evasion. In the present study, we showed that NTHi has evolved to preferentially utilize the Neu5Ac form of sialic acid. This adaptation is due to the substrate preference of the enzyme CMP-Neu5Ac synthetase, which synthesizes the activated form of Neu5Ac for macromolecule biosynthesis. This adaptation allows NTHi to evade killing by a human antibody response against the nonhuman sialic acid Neu5Gc.

Sialic Acid (N-Acetylneuraminic Acid) in Human Serum

1964 ◽  
Vol 10 (11) ◽  
pp. 986-990 ◽  
Author(s):  
J A Cabezas ◽  
J Vazquez Porto
Keyword(s):  
Sialic Acid ◽  
Rheumatic Disease ◽  
Human Serum ◽  
Spectrophotometric Method ◽  
Butyl Acetate ◽  
Normal Values ◽  
Sialic Acids ◽  
Old Adults ◽  
Acetylneuraminic Acid ◽  
Severe Burns

Abstract A simple spectrophotometric method is described for the sialic acids which utilizes the reaction with resorcinol and extraction with butyl acetate-n-butanol as a solvent. Normal values for adults, utilizing N-acetylneuraminic acid as a standard, were found to be 60 ± 10.4 mg./100 ml. Values for newborn babies averaged 40.4 ± 5.7. Similar values were found for specimens from 2-month-old infants to 27-year-old adults. Higher values were noted in the case of rickets, severe burns, rheumatic disease, and tuberculosis.

scholarly journals The Varied Role of Efflux Pumps of the MFS Family in the Interplay of Bacteria with Animal and Plant Cells

2019 ◽  
Vol 7 (9) ◽  
pp. 285 ◽  
Author(s):  
Pasqua ◽  
Grossi ◽  
Zennaro ◽  
Fanelli ◽  
Micheli ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Host Cells ◽  
Multidrug Efflux ◽  
Animal Cells ◽  
Multidrug Efflux Pumps ◽  
Wide Range ◽  
Major Facilitator

Efflux pumps represent an important and large group of transporter proteins found in all organisms. The importance of efflux pumps resides in their ability to extrude a wide range of antibiotics, resulting in the emergence of multidrug resistance in many bacteria. Besides antibiotics, multidrug efflux pumps can also extrude a large variety of compounds: Bacterial metabolites, plant-produced compounds, quorum-sensing molecules, and virulence factors. This versatility makes efflux pumps relevant players in interactions not only with other bacteria, but also with plant or animal cells. The multidrug efflux pumps belonging to the major facilitator superfamily (MFS) are widely distributed in microbial genomes and exhibit a large spectrum of substrate specificities. Multidrug MFS efflux pumps are present either as single-component transporters or as tripartite complexes. In this review, we will summarize how the multidrug MFS efflux pumps contribute to the interplay between bacteria and targeted host cells, with emphasis on their role in bacterial virulence, in the colonization of plant and animal host cells and in biofilm formation. We will also address the complexity of these interactions in the light of the underlying regulatory networks required for the effective activation of efflux pump genes.

scholarly journals Identification of anN-Acetylglucosamine Transporter That Mediates Hyphal Induction inCandida albicans

2007 ◽  
Vol 18 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Francisco J. Alvarez ◽  
James B. Konopka
Keyword(s):  
Plasma Membrane ◽  
Hyphal Growth ◽  
Nutrient Sensing ◽  
Major Facilitator Superfamily ◽  
Cellular Processes ◽  
Macrophage Phagocytosis ◽  
Wide Range ◽  
High Concentrations ◽  
Hyphal Formation ◽  
Major Facilitator

The sugar N-acetylglucosamine (GlcNAc) plays an important role in nutrient sensing and cellular regulation in a wide range of organisms from bacteria to humans. In the fungal pathogen Candida albicans, GlcNAc induces a morphological transition from budding to hyphal growth. Proteomic comparison of plasma membrane proteins from buds and from hyphae induced by GlcNAc identified a novel hyphal protein (Ngt1) with similarity to the major facilitator superfamily of transporters. An Ngt1-GFP fusion was detected in the plasma membrane after induction with GlcNAc, but not other related sugars. Ngt1-GFP was also induced by macrophage phagocytosis, suggesting a role for the GlcNAc response in signaling entry into phagolysosomes. NGT1 is needed for efficient GlcNAc uptake and for the ability to induce hyphae at low GlcNAc concentrations. High concentrations of GlcNAc could bypass the need for NGT1 to induce hyphae, indicating that elevated intracellular levels of GlcNAc induce hyphal formation. Expression of NGT1 in Saccharomyces cerevisiae promoted GlcNAc uptake, indicating that Ngt1 acts directly as a GlcNAc transporter. Transport mediated by Ngt1 was specific, as other sugars could not compete for the uptake of GlcNAc. Thus, Ngt1 represents the first eukaryotic GlcNAc transporter to be discovered. The presence of NGT1 homologues in the genome sequences of a wide range of eukaryotes from yeast to mammals suggests that they may also function in the cellular processes regulated by GlcNAc, including those that underlie important diseases such as cancer and diabetes.

scholarly journals Characterization of Glucose-Specific Catabolite Repression-Resistant Mutants of Bacillus subtilis: Identification of a Novel Hexose:H+ Symporter

1998 ◽  
Vol 180 (3) ◽  
pp. 498-504 ◽  
Author(s):  
Ian T. Paulsen ◽  
Sylvie Chauvaux ◽  
Peter Choi ◽  
Milton H. Saier
Keyword(s):  
Bacillus Subtilis ◽  
Catabolite Repression ◽  
Genetic Background ◽  
Insertional Mutagenesis ◽  
Sequence Similarity ◽  
Major Facilitator Superfamily ◽  
Phosphotransferase System ◽  
E Coli ◽  
Major Facilitator

ABSTRACT Insertional mutagenesis was conducted on Bacillus subtilis cells to screen for mutants resistant to catabolite repression. Three classes of mutants that were resistant to glucose-promoted but not mannitol-promoted catabolite repression were identified. Cloning and sequencing of the mutated genes revealed that the mutations occurred in the structural genes for (i) enzyme II of the phosphoenolpyruvate-glucose phosphotransferase (PtsG), (ii) antiterminator GlcT, which controls PtsG synthesis, and (iii) a previously uncharacterized carrier of the major facilitator superfamily, which we have designated GlcP. The last protein exhibits greatest sequence similarity to the fucose:H+ symporter ofEscherichia coli and the glucose/galactose:H+symporter of Brucella abortus. In a wild-type B. subtilis genetic background, theglcP::Tn10 mutation (i) partially but specifically relieved glucose- and sucrose-promoted catabolite repression, (ii) reduced the growth rate in minimal glucose medium, and (iii) reduced rates of [14C]glucose and [14C]methyl α-glucoside uptake. In a Δptsgenetic background no phenotype was observed, suggesting that expression of the glcP gene required a functional phosphotransferase system. When overproduced in a Δptsmutant of E. coli, GlcP could be shown to specifically transport glucose, mannose, 2-deoxyglucose and methyl α-glucoside with low micromolar affinities. Accumulation of the nonmetabolizable glucose analogs was demonstrated, and inhibitor studies suggested a dependency on the proton motive force. We conclude that B. subtilis possesses at least two distinct routes of glucose entry, both of which contribute to the phenomenon of catabolite repression.

Identification and functional characterization of Penicillium marneffei major facilitator superfamily (MFS) transporters

2020 ◽  
Vol 84 (7) ◽  
pp. 1373-1383
Author(s):  
Setyowati T. Utami ◽  
Carissa I. Indriani ◽  
Anom Bowolaksono ◽  
Takashi Yaguchi ◽  
Xinyue Chen ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Major Facilitator Superfamily ◽  
Penicillium Marneffei ◽  
Major Facilitator ◽  
Mfs Transporters

scholarly journals ThemelREDCAOperon Encodes a Utilization System for the Raffinose Family of Oligosaccharides inBacillus subtilis

2019 ◽  
Vol 201 (15) ◽  
Author(s):  
Kambiz Morabbi Heravi ◽  
Hildegard Watzlawick ◽  
Josef Altenbuchner
Keyword(s):  
Bacillus Subtilis ◽  
Transcriptional Start Site ◽  
Major Facilitator Superfamily ◽  
Atp Binding ◽  
Carbohydrate Utilization ◽  
Content Type ◽  
Storage Organs ◽  
Major Facilitator ◽  
Atp Binding Cassette

ABSTRACTBacillus subtilisis a heterotrophic soil bacterium that hydrolyzes different polysaccharides mainly found in the decomposed plants. These carbohydrates are mainly cellulose, hemicellulose, and the raffinose family of oligosaccharides (RFOs). RFOs are soluble α-galactosides, such as raffinose, stachyose, and verbascose, that rank second only after sucrose in abundance. Genome sequencing and transcriptome analysis ofB. subtilisindicated the presence of a putative α-galactosidase-encoding gene (melA) located in themsmRE-amyDC-melAoperon. Characterization of the MelA protein showed that it is a strictly Mn2+- and NAD+-dependent α-galactosidase able to hydrolyze melibiose, raffinose, and stachyose. Transcription of themsmER-amyDC-melAoperon is under control of a σA-type promoter located upstream ofmsmR(PmsmR), which is negatively regulated by MsmR. The activity of PmsmRwas induced in the presence of melibiose and raffinose. MsmR is a transcriptional repressor that binds to two binding sites at PmsmRlocated upstream of the −35 box and downstream of the transcriptional start site. MsmEX-AmyCD forms an ATP-binding cassette (ABC) transporter that probably transports melibiose into the cell. SincemsmRE-amyDC-melAis a melibiose utilization system, we renamed the operonmelREDCA.IMPORTANCEBacillus subtilisutilizes different polysaccharides produced by plants. These carbohydrates are primarily degraded by extracellular hydrolases, and the resulting oligo-, di-, and monosaccharides are transported into the cytosol via phosphoenolpyruvate-dependent phosphotransferase systems (PTS), major facilitator superfamily, and ATP-binding cassette (ABC) transporters. In this study, a new carbohydrate utilization system ofB. subtilisresponsible for the utilization of α-galactosides of the raffinose family of oligosaccharides (RFOs) was investigated. RFOs are synthesized from sucrose in plants and are mainly found in the storage organs of plant leaves. Our results revealed the modus operandi of a new carbohydrate utilization system inB. subtilis.

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