STUDY: Disinfection and healing effects of 222nm UVC light on methicillin-resistant Staphylococcus aureus infection (MRSA) in mouse wounds

Disinfection and healing effects of 222nm UVC light on methicillin-resistant Staphylococcus aureus (MRSA) infection

STUDY: Disinfection and healing effects  of 222nm UVC light on methicillin-resistant Staphylococcus aureus infection (MRSA) in mouse wounds

Originally published: January 2018 Hirosaki University and Harvard Medical School

Authors: Kouji Naritaa, Krisana Asanoa,Yukihiro Morimotod, Tatsushi Igarashid, Michael R.
Hambline, Tianhong Daie, and Akio Nakanea

• Irradiation with 222-nm UVC showed a bactericidal effect against MRSA in vivo
• Irradiation with 222-nm UVC reduced bacterial counts in MRSA-infected wounds
• 222-nm UVC light did not induce CPD in either epidermal or dermal cells, while 254-nm UVC did

UVC radiation is known to be highly germicidal. However, exposure to 254-nm-UVC light causes DNA lesions such as cyclobutane pyrimidine dimers (CPD) in human cells, and can induce skin cancer after long-term repeated exposures. It has been reported that short wavelength UVC is absorbed by proteins in the membrane and cytosol, and fails to reach the nucleus of human cells. Hence, irradiation with 222-nm UVC might be an optimum combination of effective disinfection and biological safety to human cells. In this study, the biological effectiveness of 222-nm UVC was investigated using a mouse model of a skin wound infected with methicillin-resistant Staphylococcus aureus (MRSA). Irradiation with 222-nm UVC significantly reduced bacterial numbers on the skin surface compared with non-irradiated skin. Bacterial counts in wounds evaluated on days 3, 5, 8 and 12 after irradiation demonstrated that the bactericidal effect of 222-
nm UVC was equal to or more effective than 254-nm UVC. Histological analysis revealed that migration of keratinocytes which is essential for the wound healing process was impaired in wounds irradiated with 254-nm UVC, but was unaffected in 222-nm UVC irradiated wounds. No CPD-expressing cells were detected in either epidermis or dermis of wounds irradiated with 222-nm UVC, whereas CPD-expressing cells were found in both epidermis and dermis irradiation with 254-nm UVC. These results suggest that 222-nm UVC light may be a safe and effective way to reduce the rate of surgical site and other wound infections.

Surgical site infections (SSI) are an important cause of morbidity in surgical patients and are responsible for an increased economic burden to the healthcare systems [1]. Most SSI result from commensal bacteria colonizing the patient’s own body. Staphylococcus aureus is frequently detected as a commensal skin microorganism and is the most common microbial cause of SSI, accounting for 15–20% of SSI occurring in hospitals [2, 3]. To date, methicillin-resistant S. aureus (MRSA) is a major problem worldwide. SSI caused by
MRSA has been shown to significantly increase the length of post-operative hospital stay, costs, and mortality [4, 5]. As most clinical isolates of MRSA are resistant to multiple antibiotics and other antimicrobials, options for effective antimicrobial therapy are often limited [6]. Hence novel strategies for prevention and treatment of SSI and for wound care are required.

UVC light is electromagnetic irradiation at wavelengths of 200 to 280 nm. It has been known for the last 100 years that UV light, particularly UVC in the range of 240–280 nm is highly germicidal [7]. UVC light at the 254-nm wavelength is easily produced from a lowpressure mercury vapor lamp, and is commonly used to inactivate and kill many microbial species [8, 9]. The germicidal mechanism of UVC light relies on its DNA-damaging effect caused by a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane pyrimidine dimers (CPD) (10). CPD is known to interrupt the transcription, translation, and replication of DNA, leading to cell death [9–10]. It was reported that irradiation of surgical wounds with germicidal UVC during orthopedic surgical procedures reduces the rate of SSI [11]. However, it has also been shown that exposure of human cells to 254-nm UVC causes the formation of mutagenic and cytotoxic DNA lesions, which (if repeated for a sufficiently long time) can lead to the initiation and progression of skin cancer [12].

It has been reported that penetration ability of short-UVC light (around 200–230 nm) through biological materials is very limited because short-UVC light is strongly absorbed by proteins, particularly by the peptide bonds, and other biomolecules [13, 14]. Short-UVC light is reduced by half in only about 0.3 μm of tissue [15, 16]. Buonanno et al. reported that 207-nm UVC light which is produced by krypton-bromine excimer lamp, can inactivate bacteria efficiently, moreover it also showed less cytotoxic and mutagenic damage to human
keratinocytes [17, 18]. Although the effect of 207-nm UVC light on mammalian cells in subcutaneous tissues has not yet elucidated, these reports showed that irradiation to surgical sites with 207-nm UVC light during operative procedures could be an effective strategy to prevent SSI.

Recently, a krypton-chlorine (Kr-Cl) excimer lamp was developed to emit 222-nm UVC light [19]. The germicidal and cytotoxic property of 222-nm UVC light was investigated to clarify whether this light is harmful to bacterial cells but not to human cells. To date, the use of short-UVC irradiation for treatment of wound infections remains at an early stage.

In this study, we evaluated the bactericidal and DNA-damaging effects of 222-nm UVC light in MRSAinfected wounds in a mouse model. We demonstrated that 222-nm UVC light at 75 and 150 mJ/cm2 showed the efficient bactericidal activity on normal mouse skin. Although the bactericidal activity of 222-nm UVC at 75 and 150 mJ/cm2 measured immediately after irradiation in infected wounds was comparable and slightly less than that of 254-nm UVC, respectively, the bacterial numbers in the wounds on days 5, 8 and 12 in 222-nm UVC at 150 mJ/cm2 wounds were comparable or lower than those in 254-nm UVC wounds. Importantly, DNA damage to keratinocytes and other cells in the infected wound caused by 222-nm UV light was less severe than that caused by 254-nm UVC.

General Summary

In this study, we have demonstrated that 222-nm UVC light emitted by an Xe-Cl lamp
showed effective bactericidal activity in S. aureus-infected wounds with less mutagenic and
cytotoxic effect compared to more conventional 254-nm UVC. Although further
investigations will be required for any application of 222-nm UVC light in clinical settings,
the Xe-Cl lamp has a high potential. This lamp is promising to reduce SSI and wound
infections especially by multi-drug resistance bacteria.

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