Disease relevance of PLB1

• The in vivo expression of Candida albicans secreted aspartyl proteinase (SAP1-SAP8) and phospholipase B (PLB1 and PLB2) genes was analyzed in 137 human subjects with oral and vaginal candidiasis or carriage [1].
• It appears that in oral C. albicans isolates in HIV infection there may be no significant association between the degree of PLB1 expression and other widely recognized major virulence attributes [2].
• In vivo testing demonstrated that the plb1 strain was significantly less virulent than the control strains in both the mouse inhalational model and the rabbit meningitis model [3].
• Sequence analysis revealed that McaP is related to autotransporter proteins and has substantial similarity with the GDSL family of lipolytic enzymes, particularly the Moraxella bovis phospholipase B. Expression of the mcaP gene product by E. coli increased adherence to Chang, A549, and 16HBE14o(-) polarized human bronchial cells 50- to 100-fold [4].

High impact information on PLB1

• The ability of whole blood serum to enhance binding of fibronectin was abolished by phospholipase B. These results indicate that lysophosphatidic acid derived from platelets is the principal component in whole blood serum that is active in the fibronectin binding assay [5].
• Neuropathy target esterase (NTE) was recently shown to be a phospholipase B that catalyzes production of GPC from phosphatidylcholine [6].
• Ox-LDL depleted of lysophosphatidylcholine (LPC), which was prepared by the incubation with phospholipase B, lost the stimulatory effect on PAI-1, whereas the inhibitory effect on t-PA remained present in the Ox-LDL depleted of LPC [7].
• Two lines of evidence revealed that LPA was the major factor in serum responsible for mobilizing Ca2+ in these SCLC cell lines: (a) both LPA and serum exhibited cross desensitization in the Ca2+ mobilization assay; and (b) phospholipase B pretreatment of either LPA or serum prevented the ability of these agents to stimulate Ca2+ mobilization [8].
• Binding induced by nocodazole was inhibited by the microtubule-stabilizing agent Taxol but not by pretreatment with a concentration of phospholipase B that totally abolished the stimulatory effect of LPA [9].

Biological context of PLB1

• By 3'-RACE-PCR and screening of human genome databases, we obtained a 3600 bp cDNA coding for human PLB highly homologous to already described intestinal brush border PLBs [10].
• The following report describes the use of PCR-restriction fragment length polymorphism (RFLP) analysis of the phospholipase B gene (PLB1) as a simple tool to differentiate between C. neoformans subgroups [11].
• Reintroduction of the PLB1 gene into Candida albicans restores virulence in vivo [12].
• PLB1 was located on the second smallest chromosome in both serotypes [13].
• We have shown that uptake and esterification of radiolabeled arachidonic, palmitic, and oleic acids by the Cryptococcus neoformans var. grubii H99 wild-type strain and its PLB1 deletion mutant strain (the Deltaplb1 strain) are independent of PLB1, except under hyperosmolar stress [14].

Anatomical context of PLB1

• Adhesion to lung epithelium is the first step in this process, therefore we investigated the role of PLB1 in adhesion to a human lung epithelial cell line, A549, using C. neoformans var. grubii wild-type strain H99, a PLB1 deletion mutant (Deltaplb1), and a reconstituted strain (Deltaplb1(rec)) [15].
• We conclude that PLB1 plays a role in the binding of C. neoformans to host lung epithelial cells, possibly due to production of fatty acids from plasma membranes and/or surfactant by PLB activity [15].
• Using the human macrophage-like cell line THP-1, we demonstrated the PLB1-dependent incorporation of macrophage-derived arachidonic acid into cryptococcal lipids during cryptococcus-phagocyte interaction [14].
• Similarly, PLB1 was required for metabolism of 1-palmitoyl lysophosphatidylcholine (LysoPC), which is toxic to eukaryotic cell membranes, under hyperosmolar conditions [14].
• Reduced secretion coincided with reduced enzyme in membranes and cell walls confirming a reduction in the rate of PLB1 transport to the cell surface [16].

Associations of PLB1 with chemical compounds

• Expression of PLB1 was detected in cells grown in YNB/glucose at 30 degrees C but not at 37 degrees C. However, growth of C. albicans in YNB/glucose supplemented with serum and phospholipids resulted in expression of PLB1 at 37 degrees C also [17].
• During both logarithmic and stationary phases of growth, the physiologically relevant phospholipids, dipalmitoyl phosphatidylcholine (DPPC) and dioleoyl phosphatidylcholine, were taken up and metabolized via PLB1 [14].
• Detoxification of LysoPC by reacylation occurred in both the H99 wild-type and the Deltaplb1 strains in the presence of glucose, but PLB1 was required when LysoPC was the sole carbon source [14].
• In contrast, substitution by alanine of three different serines of cPLA2 (Ser-195, Ser-215, or Ser-577) that also aligned with the PLB sequence allowed for substantial enzymatic activity of cPLA2 [18].
• The plb1 strains did not have any defects in the known cryptococcal virulence phenotypes of growth at 37 degrees C, capsule formation, laccase activity and urease activity [3].

Other interactions of PLB1

• Conditioned medium from differentiated (but not premature) adipocytes stimulated SMC proliferation, which was abolished by charcoal and proteinase K treatment but was resistant to heat, trypsin, or phospholipase B (to hydrolyze lysophosphatidic acid) [19].

Analytical, diagnostic and therapeutic context of PLB1

• RT-PCR data indicated that PLB is specifically expressed in natural and reconstructed epidermis [10].
• A highly active extracellular phospholipase, demonstrating phospholipase B (PLB), lysophospholipase (LPL) and lysophospholipase/transacylase (LPTA) activities, was purified to homogeneity from C. neoformans using (NH(4))(2)SO(4) fractionation, and hydrophobic-interaction, anion-exchange and gel-filtration chromatography [20].
• We describe for the first time the detection by ELISA of antibodies to cryptococcal phospholipase B in the serum of patients infected with C. neoformans or C. gattii [21].

References