Page 205 - The Biochemistry of Inorganic Polyphosphates

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Polyphosphates in medicine 189
similar roles seem plausible in the expression of virulence factors, which also appear in
the stationary phase of some pathogens. In mutants lacking ppk, the phenotype changes
related to virulence decrease were established. These are as follows: growth defects at the
stationary phase, defective responses to stress and starvation, higher sensitivity to stress
factors, including heat, antibiotics, antiserum, UV-light and other effectors, impairment in
motility, and biofilm formation (Ogawa et al., 2000b; Rashid and Kornberg, 2000; Rashid
et al., 2000a,b; Kim et al., 2002; Chen et al., 2002).
Some evidence for the enhanced virulence of pathogenic strains with increased polyphos-
phate kinase activity has been obtained. A deletion in the ppk gene of the Helicobacter pylori
strain Hp141 led to the higher enzymatic activity of polyphosphate kinase, and the variant
with such a deletion exhibited a better capacity for colonizing mice. Taking into account
that the modified gene is known to be involved in adaptation to a new environment, it was
suggested that PPK is an important virulence factor in H. pylori (Ayraud et al., 2003).
The genes with similarity to bacterial ppk1 and ppk2 were not found in higher eukaryotes
(Kornberg et al., 1999; Zhang et al., 2002). Because polyphosphate kinase or/and PolyP
were found necessary for virulence, polyphosphate kinase has become an attractive target
for antimicrobial drugs (Kornberg, 1999; Kornberg et al., 1999). The absence of any sim-
ilar enzyme in the higher eukaryotes makes toxicity less likely. Large-scale screening for
inhibitors of E. coli and P. aeruginosa polyphosphate kinases has given candidates which
are unique among the known kinases and active at low concentrations (Kim et al., 2002).

9.3.3 Polyphosphates as New Biomaterials
Calcium PolyP fibre has been synthesized (Griffith, 1992) and new high-performance cal-
cium polyphosphate bioceramics has been proposed as a bone-substitute material (Nelson
et al., 1993; Pilliar et al., 2001). The in vivo experiments, in which porous rods of calcium
PolyP were implanted in the distal femur of rabbits, show that these rods can support bone
ingrowth and give no adverse reaction (Grynpas et al., 2002).
A biodegradable PolyP matrix system was developed as a potential delivery vehicle for
growth factors. Polyphosphate was synthesized using a triethylamine catalyst in an argon
environment and characterized by using elemental analysis, gel permeation chromatogra-
phy, and Fourier-transform infrared spectroscopy. It was concluded that this system might be
an effective carrier for morphogens, growth factors or other classes of bioactive molecules
(Renier and Kohn, 1997). Calcium PolyP fibres were used as scaffold materials for tendon
tissue engineering in vitro (Sun and Zhao, 2002).

9.3.4 Polyphosphates in Bone Therapy and Stomathology

In view of the fact that PolyP is probably involved in the regulation of phosphate metabolism
in bone tissues (Schr¨oder et al., 1999; 2000), attempts were made to prove the potential
therapeutic uses of PolyPs in the treatment of some bone diseases.
The dissolving action of sodium PolyP 3 , cyclic trisodium phosphate and sodium PolyP
on synthetic crystals of calcium pyrophosphate dihydrate, and on crystalline aggregates
of menisci from patients with chondrocalcinosis, was determined (Cini et al., 2001). The