New antimicrobial strategies appearing out of the blue

From the photosynthetic pathways in cyanobacteria, to the germicidal effects of ultraviolet light, the biological effects of light on micro-organisms are wide-ranging, and can have either positive or negative effects on cell life. In terms of microbial inactivation, the germicidal properties of light – specifically ultraviolet light – have long been established. However, more recently, evidence of the antimicrobial effects of violet-blue light has been generating considerable attention as an alternative method for a range of antimicrobial and infection- control applications.

Bacterial inactivation using violet-blue light has emerged as an area of increasing research interest. Although less biocidal than ultraviolet (UV) light, visible violet-blue light, with particular emphasis on a narrow wavelength band centred on 405 nm, has proved effective for inactivation of a range of microbial species. The exploitation of this wavelength region may provide alternative methods of antimicrobial treatment or decontamination, in an area where novel technologies are increasingly required due to the problems of antibiotic and disinfectant resistance.

Susceptibility to violet-blue light

The biocidal effect of violet-blue light represents a photodynamic inactivation mechanism that involves the absorption of photons in the region of 405 nm by endogenous porphyrin molecules within microbial cells. This absorption initiates excitation of the porphyrin molecules, and excited porphyrins interact with oxygen or cell components to produce reactive oxygen species (ROS) causing oxidative damage and microbial cell death. Cell death has been accredited to oxidative damage to the cell membrane; however, it is likely that, due to the non-selective nature of ROS, multi-target damage will be induced in exposed microbial cells.

Laboratory studies have demonstrated the broad antimicrobial activity of 405 nm light and the wider violet-blue wavelengths for inactivation of micro-organisms in liquids, on surfaces and in biofilms. Publications have documented the susceptibility of a range of problematic bacteria of significance in the clinical environment and as food- and water-borne pathogens, such as Staphylococcus aureus including MRSA, Clostridium difficile, Escherichia coli, Pseudomonas aeruginosa, Campylocbacter jejuni and Listeria monocytogenes. Bacterial susceptibility to violet-blue light inactivation tends to be species-dependent; however, the general trend suggests that Gram-positive bacteria tend to be more susceptible to inactivation than Gram-negative species. Clostridium vegetative cells and Campylobacter species have been shown to be particularly susceptible to inactivation and this is accredited to the high sensitivity of these organisms to oxidative damage due to their aero-intolerant nature.

The effectiveness of 405 nm light for microbial inactivation has also been demonstrated against fungal organisms including moulds and yeasts such as Candida, with vegetative structures showing similar-to-increased susceptibility to that of Gram-negative bacteria. In addition to vegetative microbial cells, bacterial endospores and fungal conidiospores have demonstrated susceptibility to violet-blue light; however, as would be expected, these dormant structures display much greater resilience, requiring approximately 10 times the light energy for a similar level of inactivation. The viricial effects of violet-blue light have not yet been fully determined, although a recent study using bacteriophage demonstrated the high energies required for inactivation when suspended in minimal media – an effect that was anticipated and understandable due to the absence of porphyrins within viral structures.

Range of inactivation

Although the inactivation efficacy of violet-blue light wavelengths is much lower than that of germicidal UV-light, significant microbial inactivation can still be demonstrated, with up to 9-log₁₀ orders of bacterial reduction being recorded. However, this significant disadvantage in terms of its efficacy is balanced by the fact that the lower energy photons of violet-blue light cause less material degradation, and can, unlike germicidal UV-light, be safely utilised in the presence of people or indeed exposed mammalian tissue. These increased safety aspects, coupled with the wide antimicrobial efficacy of violet-blue light, have opened up a range of potential antimicrobial and infection-control applications for this light-based technology.

The use of violet-blue light for clinical applications has received considerable interest and various topics have been investigated. Photodynamic therapy using 405-420 nm light has proven to have bactericidal effects against Propionibacterium acnes, the causative agent in acne vulgaris, and subsequent therapeutic use of light of these wavelengths has been found to alleviate the condition. Blue light eradication of Helicobacter pylori, an organism that can colonise the human stomach and is associated with peptic ulcers, has also been demonstrated in both in vitro and in vivo studies. Due to the range of bacterial species that are successfully inactivated by violet-blue light, its potential use for wound decontamination has also been proposed in a number of publications, and the finding that bactericidal doses of violet-blue light do not appear to adversely affect mammalian cells or wound healing supports this potential application area.

A safe and clean option

The safety advantages which permit human exposure have also led to the development of an antimicrobial 405 nm light system for occupied ‘whole-room’ environmental decontamination, a research area that has been pioneered by scientists at the University of Strathclyde, and was awarded the Times Higher Education Research Project of the Year award in 2011. The work at Strathclyde has developed a ceiling-mounted lighting system that utilises 405 nm light to provide continuous decontamination of the air and exposed contact surfaces within occupied hospital wards and rooms.

Evaluation of the disinfection efficacy of the system was determined by collection of environmental samples from a range of ‘frequently touched’ contact surfaces around illuminated rooms – such as bed rails, door handles, bed table, etc. – before, during and after use of the 405 nm light system. Results from a range of hospital-based studies involving Intensive Care and Burns Units, as well as other clinical locations, have demonstrated that use of the system can significantly improve the environmental ‘cleanliness’ of the illuminated area, with bacterial contamination levels being reduced by as much as 90% in some cases. These results from extensive evaluations within the clinical environment have demonstrated that significant reductions in the levels of environmental bacterial contaminants, including transmissible pathogens, can be achieved, over and above those attainable by standard cleaning and disinfection procedures alone.

Given the increased awareness of the role that contaminated environments can play in infection transmission, particularly within the healthcare environment, the application of a technology that can provide continuous decontamination of occupied environments, whilst causing no disruption to normal activities in the room, is an area of intense interest. Although it remains to be established, it is anticipated and logical to assume that reductions in the environmental bio-burden should translate to a reduction in healthcare-associated infections arising from environmental sources, such as those transferred directly from environment to patient via contaminated surfaces or air, or indirectly via contact with healthcare workers or visitors who have unconsciously picked up contamination from the environment.

For environmental decontamination purposes, the emphasis to date has been the application of 405 nm light for hospital decontamination, but there are other areas of significant interest such as its application for maintenance of clean room sterility and for sensitive food production and preparation areas. Overall, the evidence of the antimicrobial effects of violet-blue light has opened up an area of enormous research interest, ranging from basic mechanistic studies into the photo-inactivation reaction within cells, to development of novel antimicrobial methodologies and systems. It can be anticipated that use of these safe, visible antimicrobial wavelengths will make a significant contribution to modern infection control and environmental decontamination strategies.

MICHELLE MACLEAN, JOHN G. ANDERSON & SCOTT J. MACGREGOR

The Robertson Trust Laboratory for Electronic Sterilisation Technologies (ROLEST), University of Strathclyde, Glasgow G1 1XW, UK
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FURTHER READING

Maclean, M. & others (2009). Inactivation of bacterial pathogens following exposure to light from a 405-nm LED array. Appl Environ Microbiol 75, 1932–1937.

Maclean, M. & others (2010). Environmental decontamination of a hospital isolation room using high-intensity narrow-spectrum light. J Hosp Infect 76, 247–251.

Maclean, M. & others (2014). 405 nm light technology for the inactivation of pathogens and its potential role for environmental disinfection and infection control. J Hosp Infect 88, 1–11.