White and blue light induce reduction in susceptibility to minocycline and tigecycline in Acinetobacter spp. and other bacteria of clinical importance

Abstract

Minocycline (MIN) and tigecycline (TIG) are antibiotics currently used for treatment of multidrugresistant nosocomial pathogens. In this work, we show that blue light, as well as white light, modulates susceptibility to these antibiotics in a temperature-dependent manner. The modulation of susceptibility by light depends on the content of iron; an increase in iron results in a reduction in antibiotic susceptibility both under light and in the dark, though the effect is more pronounced in the latter condition. We further provide insights into the mechanism by showing that reduction in susceptibility to MIN and TIG induced by light is likely triggered by the generation of 1 O 2 , which, by a yet unknown mechanism, would ultimately lead to the activation of resistance genes such as those coding for the efflux pump AdeABC. The clinical relevance of these results may lie in surface-exposed wound infections, given the exposure to light in addition to the relatively low temperatures recorded in this type of lesion. We further show that the modulation of antibiotic susceptibility occurs not only in Acinetobacter baumannii but also in other micro-organisms of clinical relevance such as Escherichia coli and Staphylococcus aureus. Overall, our findings allow us to suggest that MIN and TIG antibiotic treatments may be improved by the inclusion of an iron chelator, in addition to keeping the wounds in the dark, a condition that would increase the effectiveness in the control of infections involving these micro-organisms.

Light Modulates Metabolic Pathways and Other Novel Physiological Traits in the Human Pathogen Acinetobacter baumannii

“…It is also interesting that an efflux pump of the type EmrAB is upregulated by light in the context of the reduced susceptibility to minocycline (MIN) and tigecycline (TIG) we have observed under blue light (8). EmrAB can function as components of tripartite systems together with TolC, for example (e.g., EmrAB-TolC), and in this context, it has been recently shown that the TolC homolog AbuO is involved in tigecycline resistance in Acinetobacter baumannii (36).…”

“…EmrAB can function as components of tripartite systems together with TolC, for example (e.g., EmrAB-TolC), and in this context, it has been recently shown that the TolC homolog AbuO is involved in tigecycline resistance in Acinetobacter baumannii (36). EmrAB is therefore an interesting candidate to explain the reduction in susceptibility to these antibiotics in response to blue light, in addition to induction of adeABC genes previously described under this condition (8). Moreover, in this context, we present evidence here indicating that light stimulates tolerance to the fluoroquinolone ofloxacin, as is suggested by the induction of the expression of a de-N-acetylase of the PIG family by light.…”

“…Bacterial strains used in this work include A. baumannii ATCC 19606 and its derivatives: the isogenic ΔblsA mutant, which harbors a Kn cassette inserted within its coding sequence (8); the ΔblsA mutant carrying the empty pWH1266 plasmid (this work); and the ΔblsA mutant containing pWHBlsA, which expresses a wild-type copy of blsA (this work). Luria-Bertani (LB) broth and agar (Difco) were used to grow and maintain bacterial strains.…”

“…Finally, we have presented evidence indicating that light modulates susceptibility to minocycline and tigecycline antibiotics in Acinetobacter, as well as other clinically relevant pathogens, by a BlsA-independent mechanism that most likely involves induction of the expression of resistance genes by singlet oxygen (8,10).…”

“…Gaining detailed knowledge on the bacterial pathophysiology could provide other resources for control strategies. We have recently recognized a new aspect of A. baumannii physiology: its ability to perceive and respond to light-modulating aspects related to persistence in the environment, virulence against Candida albicans (7), and resistance to antibiotics (8). Indeed, we have previously shown that blue light inhibited motility and the formation of biofilms and pellicles in A. baumannii and enhanced the ability of the bacteria to kill the filamentous form of the eukaryotic fungus Candida albicans at 24°C (7).…”