Batia Lerrer

A New Ralstonia Solanacearum High-Affinity Mannose- Binding Lectin Rs-Iil Structurally Resembling the Pseudomonas Aeruginosa Fucose-Specific Lectin Pa- Iil.

The plant pathogen Ralstonia solanacearum produces two lectins, each with different affinity to fucose. We described previously the properties and sequence of the first lectin, RSL (subunit Mr 9.9 kDa), which is related to fungal lectins (Sudakevitz, D., Imberty, A., and Gilboa‐Garber, N., 2002, J Biochem 132: 353–358). The present communication reports the discovery of the second one, RS‐IIL (subunit Mr 11.6 kDa), a tetrameric lectin, with high sequence similarity to the fucose‐binding lectin PA‐IIL of Pseudomonas aeruginosa. RS‐IIL recognizes fucose but displays much higher affinity to mannose and fructose, which is opposite to the preference spectrum of PA‐IIL. Determination of the crystal structure of RS‐IIL complexed with a mannose derivative demonstrates a tetrameric structure very similar to the recently solved PA‐IIL structure (Mitchell, E., et al., 2002, Nature Struct Biol 9: 918–921). Each monomer contains two close calcium cations that mediate the binding of the monosaccharide and explain the outstandingly high affinity to the monosaccharide ligand. The binding loop of the cations is fully conserved in RS‐IIL and PA‐IIL, whereas the preference for mannose versus fucose can be attributed to the change of a three‐amino‐acid sequence in the ‘specificity loop’.

Honey and royal jelly, like human milk, abrogate lectin-dependent infection-preceding Pseudomonas aeruginosa adhesion

Pseudomonas aeruginosa antibiotic resistance has led to the search of natural compounds, which would competitively block its fucose>fructose/mannose-binding lectin (PA-IIL) that mediates its biofilm formation and adhesion to animal cells. Such compounds were found in human milk (HM) and avian egg whites. The present research has revealed that honey and royal jelly (RJ), which are assigned to protect beehive progeny and are applied for human infection therapy, match HM in PA-IIL blocking. The function of their fructose (higher in honey) and mannosylated glycoproteins (higher in RJ) as powerful decoys in PA-IIL neutralization is of ecological/biological importance and implementability for the antibacterial adhesion therapeutic strategy.

The complex role of SIRT6 in carcinogenesis

SIRT6, a member of the mammalian sirtuins family, functions as a mono-ADP-ribosyl transferase and NAD(+)-dependent deacylase of both acetyl groups and long-chain fatty acyl groups. SIRT6 regulates diverse cellular functions such as transcription, genome stability, telomere integrity, DNA repair, inflammation and metabolic related diseases such as diabetes, obesity and cancer. In this review, we will discuss the implication of SIRT6 in the biology of cancer and the relevance to organism homeostasis and lifespan.

Differential staining of western blots of avian egg white glycoproteins using diverse lectins.

Avian egg white glycoproteins which differ in structure and carbohydrate composition, vary in their interactions with diverse lectins. Generally, wheat germ agglutinin (WGA) and concanavalin A (Con A) are used for the identification and separation of those of the chicken. In the present study, interactions of a battery of lectins, including: the above two, several galactophilic lectins (from Aplysia gonad (AGL), Erythrina corallodendron (ECorL), peanut (PNA) and Pseudomonas aeruginosa (PA‐IL)), and fucose‐binding lectins (from Ulex europaeus (UEA‐I), Ulva lactuca (ULL) and P. aeruginosa (PA‐IIL), which also binds mannose) with chicken, quail and pigeon egg white glycoproteins, were examined using both hemagglutination inhibition and Western blot analyses. The chicken egg white glycoproteins interacted most strongly with WGA, followed by Con A ≫ AGL = PA‐IIL. The quail glycoprotein order of affinities was: Con A ≫ WGA = AGL = PA‐IIL, while that of the pigeon was: AGL > PA‐IL > WGA > Con A = PA‐IIL. The blocking of the other lectins by the egg whites were insignificant. The results demonstrated the selectivity and efficiency of the five most reactive lectins for differential tagging of avian egg white glycoproteins and unveiled the profound heterogeneity of the latter, as well as the possible potential lectin usage for improving purification and quality control of the desired glycoproteins.

Comparison of the antimicrobial adhesion potential of human body fluid glycoconjugates using fucose-binding lectin (PA-IIL) of Pseudomonas aeruginosa and Ulex europaeus lectin (UEA-I).

Pseudomonas aeruginosa produces a fucose-binding lectin (PA-IIL) which strongly binds to human cells. This lectin was shown to be highly sensitive to inhibition by fucose-bearing human milk glycoproteins. Since the glycans of these glycoproteins mimic human cell receptors, they may function as decoys in blocking lectin-dependent pathogen adhesion to the host cells. Human saliva and seminal fluid also contain such compounds, and body fluids of individuals who are “secretors” express additional fucosylated (alpha 1,2) residues. The latter are selectively detected by Ulex europaeus lectin UEA-I. The aim of the present research was to compare the PA-IIL and UEA-I interactions with human salivas and seminal fluids of “secretors” and “nonsecretors” with those obtained with the respective milks. Using hemagglutination inhibition and Western blot analyses, we showed that PA-IIL interactions with the saliva and seminal fluid glycoproteins were somewhat weaker than those obtained with the milk and that “nonsecretor” body fluids were not less efficient than those of “secretors” in PA-IIL blocking. UEA-I, which interacted only with the “secretors” glycoproteins, was most sensitive to those of the seminal fluids.

Breaking the Ceiling of Human Maximal Life span

While average human life expectancy has increased dramatically in the last century, the maximum life span has only modestly increased. These observations prompted the notion that human life span might have reached its maximal natural limit of ~115 years. To evaluate this hypothesis, we conducted a systematic analysis of all-cause human mortality throughout the 20th century. Our analyses revealed that, once cause of death is accounted for, there is a proportional increase in both median age of death and maximum life span. To examine whether pathway targeted aging interventions affected both median and maximum life span, we analyzed hundreds of interventions performed in multiple organisms (yeast, worms, flies, and rodents). Three criteria: median, maximum, and last survivor life spans were all significantly extended, and to a similar extent. Altogether, these findings suggest that targeting the biological/genetic causes of aging can allow breaking the currently observed ceiling of human maximal life span.