Antimicrobial Interfaces - Biointerfaces: Where Material Meets Biology - page 412

14.7.1 Role of Antibacterial Metal Ions
Novel therapeutic approach such as the gallium-based materials which act
on multiple targets of the bacterial cells would generate very low chances of
developing resistance. 130 Metabolism of iron (Fe) plays a vital role in the
vulnerability of infecting bacteria because they need Fe for growth as well as
the functioning of important enzymes; including those involved in DNA
synthesis, electron transport and oxidative stress defences. 131 Consequently,
ecient functioning of Fe metabolism is key in the pathogenesis of bacterial
infections. The ionic radius of gallium (Ga 31 ) is almost identical to that of
Fe 31 and hence it can act as a 'Trojan horse' as many biological systems are
unable to differentiate Ga 31 from Fe 31 . 132 More crucially, sequential oxi-
dation and reduction are essential for a number of the biological functions
of Fe 31 . Thus, insertion of Ga 31 can disrupt Fe 31 -dependent processes as it
cannot be reduced under the same conditions. 132 Therefore Ga 31 has
emerged as a new generation antibacterial ion that might be effective in
treating and preventing localised infections. 130,133 Much research in this
area focuses on the use of gallium complexes, including gallium mal-
tolate, 134 desferrioxamine gallium, 135 and gallium salts [e.g.,Ga(NO 3 ) 3 ]. 136
Gallium-doped phosphate-based glasses (PBGs) containing Ga 31 were re-
ported as a potent antibacterial agents against both P. aeruginosa growing
either planktonically or as biofilms. 130,137 Recently, it was shown that a
combinational approach whereby different antibacterial agents with diverse
antibacterial mechanisms such as silver (which inhibits DNA replication,
protein inactivation and destabilisation of the intercellular adhesion forces
within bacterial biofilms 138 ) and gallium (which interfere with iron-
dependent enzymes and hence could act concurrently on multiple targets 132 )
could be a promising strategy in controlling the putative periodontal
pathogen P. gingivalis. 139 Such strategies have huge potential as the mu-
tation of a single intracellular drug target might not yield high-level resist-
ance in bacteria undergoing such treatment. A protocol to evaluate cell-cell
adhesion within P. aeruginosa biofilm exposed to antibacterial metal-doped
glasses is shown in Figure 14.3. Furthermore, combined approaches were
also reported that include incorporating silver releasing ability of the sur-
faces with contact-killing capabilities of quaternary ammonium salts, 118
titanium-doped iron, silver-doped titanium, silver-doped silica films, silver-
doped phenyltriethoxysilane, silver-doped inorganic-organic hybrids, and
silver-doped HA coatings. 140,141

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14.8 Future Directions
Despite recent significant progress in the understanding of the means by
which infection develops, the design and manufacture of antibacterial sur-
faces remains a high public health and scientific research priority. The
colonisation of surfaces by bacteria is well recognised to unfavourably affect
the function of a number of specific interfaces, such as medical implants, yet