<em>In Vivo</em> Investigation of Antimicrobial Blue Light Therapy for Multidrug-resistant <em>Acinetobacter baumannii</em> Burn Infections Using Bioluminescence Imaging

Abstract

Burn infections continue to be an important cause of morbidity and mortality. The increasing emergence of multidrug-resistant (MDR) bacteria has led to the frequent failure of traditional antibiotic treatments. Alternative therapeutics are urgently needed to tackle MDR bacteria. An innovative non-antibiotic approach, antimicrobial blue light (aBL), has shown promising effectiveness against MDR infections. The mechanism of action of aBL is not yet well understood. It is commonly hypothesized that naturally occurring endogenous photosensitizing chromophores in bacteria (e.g., iron-free porphyrins, flavins, etc.) are excited by aBL, which in turn produces cytotoxic reactive oxygen species (ROS) through a photochemical process. Unlike another light-based antimicrobial approach, antimicrobial photodynamic therapy (aPDT), aBL therapy does not require the involvement of an exogenous photosensitizer. All it needs to take effect is the irradiation of blue light; therefore, it is simple and inexpensive. The aBL receptors are the endogenous cellular photosensitizers in bacteria, rather than the DNA. Thus, aBL is believed to be much less genotoxic to host cells than ultraviolet-C (UVC) irradiation, which directly causes DNA damage in host cells. In this paper, we present a protocol to assess the effectiveness of aBL therapy for MDR Acinetobacter baumannii infections in a mouse model of burn injury. By using an engineered bioluminescent strain, we were able to noninvasively monitor the extent of infection in real time in living animals. This technique is also an effective tool for monitoring the spatial distribution of infections in animals.

Photoinactivation of Moraxella catarrhalis Using 405‐nm Blue Light: Implications for the Treatment of Otitis Media

“…Previous studies both in our laboratory and other research groups demonstrated that aBL effectively eradicated a panel of clinical pathogenic microbes, including Acinetobacter baumannii , Pseudomonas aeruginosa , Candida albicans , MRSA and Neisseria gonorrhea (22‐23,25,29‐30,33‐40). In the present study, we showed that aBL was equally effective in inactivating M. catarrhalis , an otopathogen, both in suspensions and in biofilms.…”

Effects of Blue-Light-Induced Free Radical Formation from Catechin Hydrate on the Inactivation of Acinetobacter baumannii, Including a Carbapenem-Resistant Strain

“…The photochemical effect of blue light irradiation at 1.0 mW/cm 2 for 60 min (with an energy dose of 3.6 J/cm 2 ) without CHPB added achieved nearly a 9.2% inactivation rate for A. baumanni, and the rate for blue light irradiation at 2.0 mW/cm 2 for 120 min reached approximately 68.4% (at an energy dose of 14.4 J/cm 2 ) in Figure 5 . It has been reported that the utility of antimicrobial therapy for multidrug-resistant A. baumanni infection in a mouse-burned model suggests that blue light significantly reduced the bacterial burden in mouse burns by endogenous porphyrins within A. baumannii cells [ 48 , 49 ]. Endogenous intracellular porphyrins are similar to photosensitizers, in that they can be excited by blue light and, in turn, create ROS, causing cell death [ 26 ].…”

Contamination of wounds with fecal bacteria in immuno-suppressed mice

“…For basic research on bacterial infections, the use of luminescent bacterial strains and the detection by bioluminescence imaging are widely used tools 22,56,57 . However, as this procedure requires transiently transformed bacteria and in the present study we aimed to apply a complex biological sample (CS) for contamination, bioluminescence imaging was no option.…”