Total Synthesis of 6-Deoxy-l-talose Containing a Pentasaccharide Repeating Unit of Acinetobacter baumannii K11 Capsular Polysaccharides.

Herein, we report a concise synthetic approach for the first total synthesis of a pentasaccharide repeating unit of Acinetobacter baumannii K11 capsular polysaccharides containing a rare sugar 6-deoxy-l-talose. The pentasaccharide was synthesized in a convergent manner using a [3 + 2] block glycosylation strategy. During this synthetic strive, we used a 2,2,2-trichloroethoxycarbonyl (Troc)-protected monosaccharide unit to achieve a high yield during the glycosylation to synthesize a trisaccharide, and chemoselective deprotection of the Troc group from the trisaccharide was carried out under a mild, pH-neutral condition, keeping the O-glycosidic bond, azido, and acid/base sensitive group intact. A thiotolylglycoside disaccharide donor containing 6-deoxy-l-talose was synthesized for the first time by the armed-disarmed glycosylation method between two thiotolylglycosides.

Structural characterization of a novel fucosylated trisaccharide prepared from bacterial exopolysaccharides and evaluation of its prebiotic activity.

Fucosylated oligosaccharides have promising prospects in various fields. In this study, a fucosylated trisaccharide (GFG) was separated from the acidolysis products of exopolysaccharides from Clavibacter michiganensis M1. Structural characterization demonstrated that GFG consists of glucose, galactose, and fucose, with a molecular weight of 488 Da. Nuclear magnetic resonance analysis showed that it has a different structure than that of 2'-fucosyllactose (2'-FL), even though they have the same monosaccharide composition. In vitro prebiotic experiments were conducted to evaluate the differences in the utilization of three selected carbohydrates by fourteen bacterial strains. In comparison with 2'-FL, GFG could be utilized by more beneficial bacteria, leading to generate more short-chain fatty acids. Moreover, GFG could not promote the proliferation of Escherichia coli. This work describes a novel fucosylated oligosaccharide and its preparation method, and the obtained trisaccharide may serve as a promising candidate for fucosylated human milk oligosaccharides.

Synthetic Zwitterionic Streptococcus pneumoniae Type 1 Oligosaccharides Carrying Labile O-Acetyl Esters.

We herein report the first total synthesis of the Streptococcus pneumoniae serotype 1 (Sp1) oligosaccharide, a unique zwitterionic capsular polysaccharide carrying labile O-acetyl esters. The target oligosaccharides, featuring rare α-2,4-diamino-2,4,6-trideoxy galactose (AAT) and α-galacturonic acids, were assembled up to the 9-mer level, in a highly stereoselective manner using trisaccharide building blocks. The lability of the O-acetyl esters imposed a careful deprotection scheme to prevent migration and hydrolysis. The migration was investigated in detail at various pD values using NMR spectroscopy, to show that migration and hydrolysis of the C-3-O-acetyl esters readily takes place under neutral conditions. Structural investigation showed the oligomers to adopt a right-handed helical structure with the acetyl esters exposed on the periphery of the helix in close proximity of the neighboring AAT residues, thereby imposing conformational restrictions on the AATα1-4GalA(3OAc) glycosidic linkages, supporting the helical shape of the polysaccharide, that has been proposed to be critical for its unique biological activity.

Isomelezitose Overproduction by Alginate-Entrapped Recombinant E. coli Cells and In Vitro Evaluation of Its Potential Prebiotic Effect.

In this work, the trisaccharide isomelezitose was overproduced from sucrose using a biocatalyst based on immobilized Escherichia coli cells harbouring the α-glucosidase from the yeast Metschnikowia reukaufii, the best native producer of this sugar described to date. The overall process for isomelezitose production and purification was performed in three simple steps: (i) oligosaccharides synthesis by alginate-entrapped E. coli; (ii) elimination of monosaccharides (glucose and fructose) using alginate-entrapped Komagataella phaffii cells; and (iii) semi-preparative high performance liquid chromatography under isocratic conditions. As result, approximately 2.15 g of isomelezitose (purity exceeding 95%) was obtained from 15 g of sucrose. The potential prebiotic effect of this sugar on probiotic bacteria (Lactobacillus casei, Lactobacillus rhamnosus and Enterococcus faecium) was analysed using in vitro assays for the first time. The growth of all probiotic bacteria cultures supplemented with isomelezitose was significantly improved and was similar to that of cultures supplemented with a commercial mixture of fructo-oligosaccharides. In addition, when isomelezitose was added to the bacteria cultures, the production of organic acids (mainly butyrate) was significantly promoted. Therefore, these results confirm that isomelezitose is a potential novel prebiotic that could be included in healthier foodstuffs designed for human gastrointestinal balance maintenance.

Contribution of TagA-Like Glycosyltransferases to the Assembly of the Secondary Cell Wall Polysaccharide in Bacillus anthracis.

Bacillus anthracis elaborates a secondary cell wall polysaccharide (SCWP) made of 6 to 12 trisaccharide units. Pyruvyl and acetyl substitutions of the distal unit are prerequisites for the noncovalent retention of 22 secreted Bacillus S-layer (Bsl)-associated proteins bearing an S-layer homology (SLH) domain. Surface display of Bsl proteins contributes to cell separation as well as virulence. Earlier work suggested that TagO initiates the synthesis of SCWP while GneY and GneZ, two UDP-GlcNAc 2-epimerases, synthesize ManNAc that is later incorporated in the repeat unit (→4)-ManNAc-(ß1→4)-GlcNAc-(ß1→6)-GlcNAc-(α1→). In organisms that synthesize wall teichoic acid, TagA catalysts have been shown to form the glycosidic bond ManNAc-(ß1→4)-GlcNAc. Here, we show that genes bas2675 and bas5272, predicted to encode glycosyltransferases of the WecB/TagA/CpsF family (PFAM03808; CAZy GT26), are required for B. anthracis SCWP synthesis and S-layer assembly. Similar to tagO or gneY gneZ mutants, B. anthracis strains depleted of tagA1 (bas5272) cannot maintain cell shape, support vegetative growth, or synthesize SCWP. Expression of tagA2 (bas2675), or Staphylococcus aureus tagA on a plasmid, rescues the nonviable tagA1 mutant. We propose that TagA1 and TagA2 fulfill overlapping and key glycosyltransferase functions for the synthesis of repeat units of the SCWP of B. anthracis. IMPORTANCE Glycosyltransferases (GTs) catalyze the transfer of sugar moieties from activated donor molecules to acceptor molecules to form glycosidic bonds using a retaining or inverting mechanism. Based on the structural relatedness of their catalytic and carbohydrate-binding modules, GTs have been grouped into 115 families in the Carbohydrate-Active EnZyme (CAZy) database. For complex products, the functional assignment of GTs remains highly challenging without the knowledge of the chemical structure of the assembled polymer. Here, we propose that two uncharacterized GTs of B. anthracis belonging to the WecB/TagA/CpsF family incorporate ManNAc in repeat units of the secondary cell wall polymer of bacilli species.

Direct Synthesis of 2,6-Dideoxy-ß-glycosides and ß-Rhamnosides with a Stereodirecting 2-(Diphenylphosphinoyl)acetyl Group.

Anomeric stereocontrol is usually one of the major issues in the synthesis of complex carbohydrates, particularly those involving ß-configured 2,6-dideoxyglycoside and d/l-rhamnoside moieties. Herein, we report that 2-(diphenylphosphinoyl)acetyl is highly effective as a remote stereodirecting group in the direct synthesis of these challenging ß-glycosides under mild conditions. A deoxy-trisaccharide as a mimic of the sugar chain of landomycin E was prepared stereospecifically in high yield. The synthetic potential was also highlighted in the synthesis of Citrobacter freundii O-antigens composed of a [→4)-α-d-Manp-(1→3)-ß-d-Rhap(1→4)-ß-d-Rhap-(1→] repeating unit, wherein the convergent assembly up to a nonasaccharide was realized with a strongly ß-directing trisaccharide donor. Variable-temperature NMR studies indicate the presence of intermolecular H-bonding between the donor and the bulky acceptor as direct spectral evidence in support of the concept of hydrogen-bond-mediated aglycone delivery.

Practical non-enzymatic synthesis of propargyl sialyl-α-(2-3')-lactosamine trisaccharide using minimal protecting groups manipulation.

The trisaccharide, prop-2-ynyl 5-acetamido-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonic acid-(2 â†’ 3)-ß-d-galactopyranosyl-(1 â†’ 4)-2-acetamido-2-deoxy-ß-d-glucopyranoside (9) has been efficiently synthesized in a few steps without the need of conformationally constrained glycosyl donors and acceptors or enzymes. First, using the known prop-2-ynyl 2-acetamido-2-deoxy-6-O-tert-butyldiphenylsilyl-ß-d-glucopyranoside as acceptor (2) and the peracetylated galactosyl trichloroacetimidate (3) as glycosyl donor, followed by protecting groups manipulation, prop-2-ynyl (6-O-tert-butyldiphenylsilyl-ß-d-galactopyranosyl)-(1 â†’ 4)-2-acetamido-2-deoxy-6-O-tert-butyldiphenylsilyl-ß-d-glucopyranoside (6) was synthesized with exclusive O-4 regioselectivity due to steric hindrance of the upper face of the acceptor at O-3. Sialylation with the thiophenyl glycosyl donor (7) afforded the desired trisaccharide with the shortest number of steps and in higher overall yield than previously reported methodologies. The direct use of minimally protected N-acetyl-lactosamine acceptor (6) was critical for the efficient synthesis of the title compound. The propargylic aglycone is suitable for chemical ligation using click chemistry as reported for its (2 â†’ 6) sialylated analog.

A Novel Alginate Lyase: Identification, Characterization, and Potential Application in Alginate Trisaccharide Preparation.

Alginate oligosaccharides (AOS) have many biological activities and significant applications in prebiotics, nutritional supplements, and plant growth development. Alginate lyases have unique advantages in the preparation of AOS. However, only a limited number of alginate lyases have been so far reported to have potentials in the preparation of AOS with specific degrees of polymerization. Here, an alginate-degrading strain Pseudoalteromonasarctica M9 was isolated from Sargassum, and five alginate lyases were predicted in its genome. These putative alginate lyases were expressed and their degradation products towards sodium alginate were analyzed. Among them, AlyM2 mainly generated trisaccharides, which accounted for 79.9% in the products. AlyM2 is a PL6 lyase with low sequence identity (≤28.3%) to the characterized alginate lyases and may adopt a distinct catalytic mechanism from the other PL6 alginate lyases based on sequence alignment. AlyM2 is a bifunctional endotype lyase, exhibiting the highest activity at 30 °C, pH 8.0, and 0.5 M NaCl. AlyM2 predominantly produces trisaccharides from homopolymeric M block (PM), homopolymeric G block (PG), or sodium alginate, with a trisaccharide production of 588.4 mg/g from sodium alginate, indicating its promising potential in preparing trisaccharides from these polysaccharides.

Synthesis of globotriose-modified peptides for the preparation of a colorimetric biosensor to detect Shiga toxins.

Globotriose (Gal-α1, 4-Gal-ß1, 4-Glc) is involved in binding with Shiga toxins (Stxs) produced by Shigella dysenteriae and certain pathogenic Escherichia coli strains which could cause severe gastroenteritis and hemolytic uremic syndrome (HUS). Thus, this trisaccharide group and its derivatives provide potentials in the development of carbohydrate-based diagnostic and therapeutic reagents against bacterial infection. Instead of the tedious chemical synthesis of globotriose or its glycoconjugates, we reported a multi-step (step-wise) enzymatic synthesis system containing glucosyltransferase (ApNGT, E.C. 4.3.3.5), ß-1, 4-galactosyltransferase (LgtB, E.C. 2.4.1.22) and α-1, 4-galactosyltransferase (LgtC, E.C. 2.4.1.44) to produce globotriose-containing glycopeptides. In addition, based on the specific binding between Stxs and globotriose, a cost-efficient, convenient, ultra-sensitive and specific colorimetric biosensor was further constructed to detect Stxs using glycoconjugated Au@Fe-TFPA-COP (globotriose@Au@Fe-TFPA-COP) as a nanoenzyme catalyst. We estimate that this method conveniently applied in the detection of Stx-producing bacteria and associated infectious diseases.

Synthesis of a library of 2-fluoro-2-deoxy-derivatives of the trimannoside methyl α-D-Man-(1 → 3)-[α-D-Man-(1 → 6)]-α-D-Man and the dimannosides methyl α-D-Man-(1 → 3)-α-D-Man and methyl α-D-Man-(1 → 6)-α-D-Man.

A library of sixteen compounds, 1-16, comprising all (mono-, di-, and tri-) 2-fluoro-2-deoxy-derivatives of the N-glycan core trimannoside α-D-Man-(1 â†’ 3)-[α-D-Man-(1 â†’ 6)]-D-Man, including the corresponding 2-fluoro-2-deoxy disaccharide part structures and the non-fluorinated parent compounds, have been synthesized as their α-methyl glycosides for use as tools in 19F NMR-based lectin-carbohydrate interaction studies. Two methyl 2-fluoro-2-deoxy-mannoside acceptors, 21 (3-OH) and 22 (6-OH), were constructed and used in combination with the corresponding non-fluorinated mannose acceptors, 24 (6-OH) and 25 (3-OH), the 2-fluoro-2-deoxy mannosyl bromide donor 18 and the non-fluorinated bromide donor 23 to efficiently afford the target di-and trisaccharides (disaccharides, 2-3 steps, 47-66% overall yield; trisaccharides, 4 steps, 25-40% overall yield).

Paludibacter propionicigenes GH10 xylanase as a tool for enzymatic xylooligosaccharides production from heteroxylans.

Bioconversion of lignocellulosic biomass into value-added products relies on polysaccharides depolymerization by carbohydrate active enzymes. This work reports biochemical characterization of Paludibacter propionicigenes xylanase from GH10 (PpXyn10A) and its application for enzymatic xylooligosaccharides (XOS) production from commercial heteroxylans and liquor of hydrothermally pretreated corn cobs (PCC). PpXyn10A is tolerant to ethanol and NaCl, and releases xylobiose (X2) and xylotriose (X3) as the main hydrolytic products. The conversion rate of complex substrates into short XOS was approximately 30% for glucuronoxylan and 8.8% for rye arabinoxylan, after only 4 h; while for PCC, PpXyn10A greatly increased unbranched XOS yields. B. adolescentis fermentation with XOS from beechwood glucuronoxylan produced mainly acetic and lactic acids. Structural analysis shows that while the glycone region of PpXyn10A active site is well preserved, the aglycone region has aromatic interactions in the +2 subsite that may explain why PpXyn10A does not release xylose.

Understanding the Xylooligosaccharides Utilization Mechanism of Lactobacillus brevis and Bifidobacterium adolescentis: Proteins Involved and Their Conformational Stabilities for Effectual Binding.

Xylooligosaccharides having various degrees of polymerization such as xylobiose, xylotriose, and xylotetraose positively affect human health by interacting with gut proteins. The present study aimed to identify proteins present in gut microflora, such as xylosidase, xylulokinase, etc., with the help of retrieved whole-genome annotations and find out the mechanistic interactions of those with the above substrates. The 3D structures of proteins, namely Endo-1,4-beta-xylanase B (XynB) from Lactobacillus brevis and beta-D-xylosidase (Xyl3) from Bifidobacterium adolescentis, were computationally predicted and validated with the help of various bioinformatics tools. Molecular docking studies identified the effectual binding of these proteins to the xylooligosaccharides, and the stabilities of the best-docked complexes were analyzed by molecular dynamic simulation. The present study demonstrated that XynB and Xyl3 showed better effectual binding toward Xylobiose with the binding energies of - 5.96 kcal/mol and - 4.2 kcal/mol, respectively. The interactions were stabilized by several hydrogen bonding having desolvation energy (- 6.59 and - 7.91). The conformational stabilities of the docked complexes were observed in the four selected complexes of XynB-xylotriose, XynB-xylotetraose, Xyl3-xylobiose, and Xyn3-xylotriose by MD simulations. This study showed that the interactions of these four complexes are stable, which means they have complex metabolic activities among each other. Extending these studies of understanding, the interaction between specific probiotics enzymes and their ligands can explore the detailed design of synbiotics in the future.

The Synthesis of Blood Group Antigenic A Trisaccharide and Its Biotinylated Derivative.

Blood group antigenic A trisaccharide represents the terminal residue of all A blood group antigens and plays a key role in blood cell recognition and blood group compatibility. Herein, we describe the synthesis of the spacered A trisaccharide by means of an assembly scheme that employs in its most complex step the recently proposed glycosyl donor of the 2-azido-2-deoxy-selenogalactoside type, bearing stereocontrolling 3-O-benzoyl and 4,6-O-(di-tert-butylsilylene)-protecting groups. Its application provided efficient and stereoselective formation of the required α-glycosylation product, which was then deprotected and subjected to spacer biotinylation to give both target products, which are in demand for biochemical studies.

Human Milk Oligosaccharide 2'-Fucosyllactose Induces Neuroprotection from Intracerebral Hemorrhage Stroke.

Intracerebral hemorrhage (ICH) occurs when brain blood vessels rupture, causing inflammation and cell death. 2-Fucosyllactose (2FL), a human milk oligosaccharide, has potent antiapoptotic and anti-inflammatory effects. The purpose of this study was to examine the protective effect of 2FL in cellular and rodent models of ICH. Hemin was added to a primary rat cortical neuronal and BV2 microglia coculture to simulate ICH in vitro. IBA1 and MAP2 immunoreactivities were used to determine inflammation and neuronal survival. Hemin significantly increased IBA1, while it reduced MAP2 immunoreactivity. 2FL significantly antagonized both responses. The protective effect of 2FL was next examined in a rat ICH model. Intracerebral administration of type VII collagenase reduced open-field locomotor activity. Early post-treatment with 2FL significantly improved locomotor activity. Brain tissues were collected for immunohistochemistry and qRT-PCR analysis. 2FL reduced IBA1 and CD4 immunoreactivity in the lesioned striatum. 2FL downregulated the expression of ER stress markers (PERK and CHOP), while it upregulated M2 macrophage markers (CD206 and TGFß) in the lesioned brain. Taken together, our data support that 2FL has a neuroprotective effect against ICH through the inhibition of neuroinflammation and ER stress. 2FL may have clinical implications for the treatment of ICH.

Design and evaluation of glutathione responsive glycosylated camptothecin nanosupramolecular prodrug.

A novel tumor-targeted glutathione responsive Glycosylated-Camptothecin nanosupramolecular prodrug (CPT-GL NSp) was designed and fabricated via a disulfide bond. The effects of glycoligand with different polarities on solubility, self-assembly, stability, cellular uptake, and glutathione responsive cleaving were explored, and an optimal glycosylated ligand was selected for nanosupramolecular prodrug. It has been found that CPT-GL NSp exhibited higher drug loading than traditional nanoparticles. Among of which maltose modified NSp had the strongest anti-tumor effects than that of glucose and maltotriose. CPT-SS-Maltose had a similar anti-tumor ability to Irinotecan (IR), but the superior performance in solubility, hemolysis, and uptake of HepG2 cells.

Total Synthesis of the Phosphorylated Zwitterionic Trisaccharide Repeating Unit of Photorhabdus temperata cinerea 3240.

Herein, we report the total synthesis of the phosphorylated zwitterionic trisaccharide repeating unit of Photorhabdus temperata subsp. cinerea 3240. The efficient route involves regio- and stereoselective assembly of trisaccharide with rare deoxyamino sugar AAT at the nonreducing end, late stage oxidation, and installation of a phosphate linker on the trisaccharide. The total synthesis was completed via a longest linear sequence of 24 steps in 6.5% overall yield.

Structural characterization of oligosaccharides from free radical depolymerized fucosylated glycosaminoglycan and suggested mechanism of depolymerization.

Free radical depolymerization is a common method in structural analysis of polysaccharides, the major challenge is the analysis of the cleavage site and characterization of newly formed ends in this reaction. Here, a fucosylated glycosaminoglycan from H. fuscopunctata (HfFG) was depolymerized by H2O2 and a series of oligosaccharides were purified and their structures were elucidated. For non-reducing ends of the trisaccharides were intact GalNAc4S6S, the cleavage site should mainly be the ß(1,3) linkages between GlcA and GalNAc in the backbone of FG. Meanwhile, the reducing ends of the disaccharides and trisaccharides were almost dicarboxylic acid derivatives of GlcA, possibly arising from oxidative breaking of the CC bond of GlcA at the reducing ends. In addition, glycosidic linkages in D-GalNAc-ß(1,4)-D-GlcA and L-FucS-α(1,3)-D-GlcA located at the reducing end could be cleaved, and the released GalNAc4S6S were oxidized to N-acetylgalactosaminic acid.

Total Synthesis of the Photorhabdus temperata ssp. Cinereal 3240 Zwitterionic Trisaccharide Repeating Unit.

Zwitterionic carbohydrate modifications, such as phosphoethanolamine (PEtN), govern host-pathogen interactions. Whereas it is recognized that these modifications stimulate the host immune system, the purpose of PEtN modification remains largely descriptive. As an enabling step toward studying this carbohydrate modification, we report a synthesis of the P. temperata zwitterionic trisaccharide repeating unit. The 32-step synthesis was enabled by H-phosphonate chemistry to install the PEtN arm on a poorly reactive and sterically hindered C4-alcohol.

Effects of various polysaccharides (alginate, carrageenan, gums, chitosan) and their combination with prebiotic saccharides (resistant starch, lactosucrose, lactulose) on the encapsulation of probiotic bacteria Lactobacillus casei 01 strain.

The probiotics are extremely sensitive to various environmental factors, which imposes limitation on their health and functional effectiveness. Thus, development of delivery system for protection of viable cells while passing through different stages of the human digestion system is key factor in application of probiotic products. In our study, the effects of several polysaccharides such as alginate, κ-carrageenan, locust bean gum, gellan gum, xanthan gum and their combination with various prebiotic components (resistant starch, lactulose, lactosucrose) on encapsulation of probiotic Lactobacillus casei 01 strain were studied. Both regular and unregular beads with size distributions from 2 mm up to 5 mm were obtained. The encapsulation efficiencies varied from 64.4% up to 79%. Based on the texture's profiles, the capsules can be grouped into 5 clusters with squared Euclidean distance 3.5. Meanwhile, the starch-alginate and the lactosucrose LS55L - alginate beads were found to be the most stable and to have massive textural properties, whereas the gellan gum - xanthan gum and the chitosan coated alginate beads emerged as the softest. Encapsulation significantly improved the degree of gastric tolerance of probiotic cells even in the presence of pepsin. The INFOGEST in vitro digestion protocol was adapted to investigate the protection effects of different capsules. The highest survival (with loss rate of lower than 1 log CFU/g) was observed in the case of the cells encapsulated in starch-alginate beads. Moreover, the alginate microcapsules combined with lactosucrose LS55L also provided very promising shield for probiotics from the low pH of gastric conditions. Our findings suggest that incorporation of prebiotics into alginate-base encapsulation would be good idea in development of micro delivery systems that helps the survival of probiotics and their delivery to the target sites of action in human body.

Dissection of the anti-Candida albicans mannan immune response using synthetic oligomannosides reveals unique properties of ß-1,2 mannotriose protective epitopes.

Candida albicans mannan consists of a large repertoire of oligomannosides with different types of mannose linkages and chain lengths, which act as individual epitopes with more or less overlapping antibody specificities. Although anti-C. albicans mannan antibody levels are monitored for diagnostic purposes nothing is known about the qualitative distribution of these antibodies in terms of epitope specificity. We addressed this question using a bank of previously synthesized biotin sulfone tagged oligomannosides (BSTOs) of α and ß anomery complemented with a synthetic ß-mannotriose described as a protective epitope. The reactivity of these BSTOs was analyzed with IgM isotype monoclonal antibodies (MAbs) of known specificity, polyclonal sera from patients colonized or infected with C. albicans, and mannose binding lectin (MBL). Surface plasmon resonance (SPR) and multiple analyte profiling (MAP) were used. Both methods confirmed the usual reactivity of MAbs against either α or ß linkages, excepted for MAb B6.1 (protective epitope) reacting with ß-Man whereas the corresponding BSTO reacted with anti-α-Man. These results were confirmed in western blots with native C. albicans antigens. Using patients' sera in MAP, a significant correlation was observed between the detection of anti-mannan antibodies recognizing ß- and α-Man epitopes and detection of antibodies against ß-linked mannotriose suggesting that this epitope also reacts with human polyclonal antibodies of both specificities. By contrast, the reactivity of human sera with other α- and ß-linked BSTOs clearly differed according to their colonized or infected status. In these cases, the establishment of an α/ß ratio was extremely discriminant. Finally SPR with MBL, an important lectin of innate immunity to C. albicans, classically known to interact with α-mannose, also interacted in an unexpected way with the protective epitope. These cumulative data suggest that structure/activity investigations of the finely tuned C. albicans anti-mannose immune response are worthwhile to increase our basic knowledge and for translation in medicine.