Biomedical Engineering Reference
In-Depth Information
bacteria secrete quorum sensing and other antifungal molecules (e.g., homoserine
lactones and phenazines secreted by
Pseudomonas aeruginosa
, mutanobactins
secreted by
Streptococcus mutans
) that inhibit or kill
C. albicans
biofilms (Gibson
et al.
2009
; Hogan et al.
2004
; Joyner et al.
2010
; Morales et al.
2010
; Wang
et al.
2012
).
Photodynamic therapy (PDT), mediated by the action of reactive oxygen species
generated by the photoactivation of a photosensitizer by a light source, represents a
relatively new therapeutic technique with potential applications for the treatment of
fungal biofilm infections, in particular superficial mycoses such as denture stoma-
titis and oropharyngeal candidiasis (Costa et al.
2013
; Junqueira et al.
2012
; Pereira
et al.
2011
). Another potential strategy, which may be particularly relevant in the
case of catheter-associated biofilm infections, is to target dispersion, as fungal cells
dispersed from the biofilms are responsible for fungemia, dissemination,
extravasation, and ultimately the establishment of foci of invasive mycoses at
distal organs, which are the forms associated with the highest mortality rates
(Uppuluri et al.
2010a
).
5 A Nano-Biofilm Chip for High-Throughput Antifungal
Drug Discovery
One of the main impediments for the development of newer antibiotics, including
antifungals, has been the fact that conventional microbiological culture techniques
are mostly incompatible with modern methodologies for drug discovery that are
dominated by high-throughput screening (HTS) and its “hunger for speed.” To
overcome this major bottleneck, Srinivasan and colleagues recently described the
nanoscale culture of
C. albicans
, on a microarray platform (Srinivasan et al.
2011
,
2013
). The microarray, designated
Ca
BChip (for
Candida albicans
Biofilm Chip),
consisted of a standard microscope slide containing 1,200 individual
C. albicans
biofilms (“nano-biofilms”), each with a volume of approximately 30 nL, encapsu-
lated in an inert alginate matrix (see Fig.
3
). The authors demonstrated that these
nano-biofilms, despite a 3,000-fold miniaturization over conventional biofilms
(formed on microtiter plates), are similar in their morphological, architectural,
growth, and phenotypic characteristics, including antifungal drug resistance
(Srinivasan et al.
2011
,
2013
). The nanobiofilm chip is amenable to automation
and is fully compatible with standard microarray technology and equipment. It
allows for rapid and easy handling, minimizing manual labor, and drastically
reducing assay costs (Srinivasan et al.
2011
,
2013
). It enables true high-throughput
screening in the search for new anti-biofilm drugs. The techniques should be
adaptable to other biofilm-forming species, including polymicrobial biofilms, and
should accelerate the antifungal drug discovery process by permitting fast, efficient,
and economical screening of thousands of compounds.
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