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Editorial
Antimicrobial Blue Light:
An Emerging Alternative to Antibiotics
Chukuka S. Enwemeka, PhD, FACSM
Bacterial resistance to drugs poses a major healthcare
problem, causing widespread epidemic of diseases that
hitherto were susceptible to antibiotics. Since penicillin was
introduced in the 1940s, the pharmaceutical industry has
countered this trend with periodic development and de-
ployment of ‘‘stronger’’ antibiotics; however, bacteria in
general, and methicillin-resistant Staphylococcus aureus
(MRSA) in particular, have continually evolved a repertoire
of evasive mechanisms that frequently defy antibiotic
treatment. More than two billion people now carry some
strain of S. aureus; 53 million of whom have MRSA.
1
Esti-
mates indicate that the United States alone spends 3.2–4.2
billion dollars on hospitalized patients with MRSA every
year,
2,3
and this does not include the human costs associated
with lost labor, and lost lives, which now exceed that caused
by HIV/AIDS.
4
Deadly outbreaks of MRSA have been reported in every
region of the world, with air travel and sociopolitical ties
speeding the spread and resulting in the emergence of similar
strains in countries with historical ties.
3
Whereas infections
were once confined to hospitals, that is, hospital-associated
MRSA (HA-MRSA), the ongoing spread of community-
associated MRSA (CA-MRSA) and livestock associated
MRSA (LA-MRSA), and the reported jump of strains from
animal to human and vice versa,
5–9
now present a larger
clinical conundrum. Pandemic strains of CA-MRSA have
been found on beaches, computer keyboards, locker rooms,
schools, athletic fields, and other common locations.
10–13
It is
now estimated that MRSA infection accounts for 44% of all
hospital-associated infections in the United States; of these, as
many as 92% are CA-MRSA.
14
The continuing resistance of MRSA and other bacteria to
antibiotics calls for a paradigm shift in the quest for therapies
capable of stemming their spread. Alternative modalities
currently under investigation include hyperbaric oxygen,
15
photodynamic therapy (PDT),
16
antibacterial clays,
17
and
blue light phototherapy.
18–20
Interest in hyperbaric oxygen
has waned, because of its moderate bactericidal effect com-
pared with other emerging alternatives, such as PDT, anti-
bacterial clay, and blue light. As shown in this issue of the
journal, PDT, when used as an adjunct to conventional oral
disinfection protocols, significantly reduces infection caused
by ontopathogenic bacteria, including Aggregatibacter actino-
mycetemcomitans, Porphyromonas gingivalis, and Prevotella in-
termedia.
21
Moreover, the report shows that PDT kills
cariogenic bacteria, including Streptococcus mutans and
Streptococcus sanguis, as well as bacteria associated with in-
fected root canals and peri-implantitis.
21
This finding is supported by the work of Gacez et al.
22
(in
this issue), who showed that PDT, using 660 nm diode laser
and methylene blue, significantly reduced infection in hu-
man root canals inoculated with Pseudomonas aeruginosa or
Enterococcus faecalis. Similarly, PDT has been shown to be
beneficial in treating dermatologic and ophthalmologic dis-
orders.
23,24
However, serious concerns remain for its acute
side effects and the non-targeted nature of available photo-
sensitizers.
24
This situation calls for other alternatives to
PDT, in spite of its beneficial antimicrobial effect. The Ebers
Papyrus, published circa 1600 BCE,
25
and the 5000-year-old
tablets of Nippur
26
identified clay and sunlight as therapies
used by humans to treat a wide range of diseases, including
infections caused by bacteria. Emerging reports now show
that certain types of clay and light in the ultraviolet (UV),
violet, and blue spectra have antibacterial properties.
18–20,27
In this issue of the journal, we focus on articles that indicate
that certain wavelengths of light are bactericidal and can
eradicate recalcitrant bacteria in vitro and in vivo.First,a
connection between light therapy and the antimicrobial action
of clay may be seen in the work of Lipovsky et al.
28
(in this
issue) who showed that doping nanoparticles such as ZnO,
CuO, and TiO
2,
with transition metals ions, or attaching the
metal oxides nanoparticles to an organic molecule, enhances
their antimicrobial reactive oxygen species (ROS) generation
activity when irradiated with light in the visible and near
infrared ranges. Furthermore, they found that ZnO and TiO
2
nanoparticles had notable absorption in the blue spectrum,
indicating that visible light could be used to trigger ROS
production, and, hence, the antimicrobial effect of metal ox-
ides. Studies of clay treatment similarly show that mineral
leachates, including ions of copper, iron, cobalt, nickel, and
zinc, from certain varieties of clay, are responsible for the
antibacterial action of clay against Escherichia coli and MRSA.
17
That light may be equally involved in clay treatment remains
unexplored, but a potential role cannot be ruled out entirely.
Similarly, encouraging data from Dai et al.,
29
(in this issue)
indicate that the bacteria- eradicating effect of blue light, long
reported in a multitude of in vitro studies,
18–20,27
is achievable
in vivo. They found that irradiation with 415 –10 nm blue
College of Health Sciences. University of Wisconsin—Milwaukee, Milwaukee, Wisconsin.
Photomedicine and Laser Surgery
Volume 31, Number 11, 2013
ªMary Ann Liebert, Inc.
Pp. 1–3
DOI: 10.1089/pho.2013.9871
1
light reduced bacterial burden in abrasive skin wounds of
laboratory rats inoculated with CA-MRSA. Furthermore,
bacterial clearance was achieved without significant adverse
effect on keratinocytes co-cultured with CA-MRSA. And
electron microscopy revealed that irradiation of the bacteria
caused extrusions of cytoplasmic content, cell wall damage,
and cell debris, providing an insight into the potential
mechanisms involved in photo-eradication of MRSA. How-
ever, these results are achievable only with certain parame-
ters, as suggested by the preliminary findings of Lanzafame
et al.,
30
(in this issue) who found significant reduction of
bacteria with photo-activated collagen-embedded flavins
(PCF) treatment, but not with 455 –5 nm blue light irradia-
tion alone, when treating pressure ulcers in mice inoculated
with MRSA. The implication is that experimental model and
mode of treatment can significantly affect the results ob-
tained in these types of studies.
Further evidence that experimental parameters influence
outcomes can be seen in the work of Bumah et al.
31
and Kim
et al.
32
For example, Bumah et al.
31
showed that irradiation
with either 405 or 470 nm blue light cleared MRSA pro-
gressively as fluence increased, and also as bacterial density
increased, even though the proportion of bacterial colonies
cleared decreased inversely as bacterial density. Whereas
both wavelengths had similar effects on less dense cultures,
that is, 3 ·10
6
colony-forming units (CFU)/mL and 5 ·10
6
CFU/mL cultures, 405 nm light cleared more bacteria in the
denser 7 ·10
6
CFU/mL culture. And regardless of wave-
length, more bacteria were cleared when the culture plates
were irradiated from above and below instead of being ir-
radiated from one direction at the same corresponding total
dose. The latter finding suggests that the bactericidal effect of
light-emitting diode (LED) blue light is limited more by the
ability of blue light to penetrate the layers of bacteria than by
bacterial density alone. That wavelength affects the outcome
of LED photo-irradiation of bacteria is corroborated by Kim
et al.
32
They showed that, even though P. gingivalis and
E. coli are killed with 425 nm blue light, 525 nm green light
only induces bacteriostatic effect. Also, 625 nm red light did
not kill any of the bacteria tested.
Collectively, these reports present further evidence that
light, in particular, blue light in the range of 405–470 nm
wavelength is bactericidal, and has the potential to help stem
the ongoing pandemic of MRSA and other bacterial infections.
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2 ENWEMEKA
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Address correspondence to:
Chukuka S. Enwemeka
College of Health Sciences
University of Wisconsin—Milwaukee
2400 E. Hartford Avenue
Milwaukee, WI 53211
E-mail: Enwemeka@uwm.edu
ANTIMICROBIAL BLUE LIGHT 3