The main cause of morbidity and mortality in cystic fibrosis (CF) sufferers is progressive pulmonary damage caused by
recurrent and often unremitting respiratory tract infection. Causative organisms include Pseudomonas aeruginosa and
Haemophilus influenzae, but in recent years the Burkholderia cepacia complex has come to the fore. This group of
highly drug-resistant Gram-negative bacteria are associated with a rapid decline in lung function and the often fatal
cepacia syndrome, with treatment limited to patient segregation and marginally effective antibacterial regimens. Thus,
development of an effective treatment is of the upmost importance. PACT, a non-target specific therapy, has proven
successful in killing both Gram-positive and Gram-negative bacteria. In this study, planktonic cultures of six strains of
the B. cepacia complex were irradiated (635 nm, 200 J cm-2,10 minutes irradiation) following 30 seconds incubation
with methylene blue (MB) or meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP). Rates of kill of > 99 %
were achieved with MB- and TMP-PACT. A MB concentration of 50 μg ml-1 and TMP concentration of 500 μg ml-1
were associated with highest percentage kills for each photosensitizer. PACT is an attractive option for treatment of
B.cepacia complex infection. Further study, involving biofilm culture susceptibility, delivery of light to the target and
in vivo testing will be necessary before it PACT becomes a viable treatment option for CF patients who are colonised or
infected with B. cepacia complex.
In PACT, a combination of a sensitising drug and visible light cause the selective destruction of microbial cells via
singlet oxygen production. As singlet oxygen is a non-specific oxidizing agent and is only present during illumination,
development of resistance to this treatment is thought to be unlikely. However, in response to oxidative stress, bacteria
can up-regulate oxidative stress genes and associated antibiotic resistance genes. The up-regulation of these genes and
potential transfer of genetic material may result in a resistant bacterial population. This study determined whether
treatment of clinically isolated meticillin resistant Staphylococcus aureus (MRSA) strains with sub-lethal doses of
methylene blue (MB) and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP)-PACT resulted in reduced
susceptibility to antibiotics and previously lethal PACT. Exposure of strains to sub-lethal doses of photosensitizer in
combination with light had no effect on susceptibility to previously lethal photosensitization. Furthermore, exposure to
sub-lethal concentrations of both photosensitizers caused no significant changes in the minimum inhibitory concentration
(MIC) for each strain tested. Any differences in susceptibility were not significant as they did not cross breakpoints
between resistant and susceptible for any organism or antibiotic tested. Therefore, PACT remains an attractive
alternative option for treatment of MRSA infections.
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