Revisiting methylene blue: recent advances towards pathogenic microorganisms

Antimicrobial photodynamic therapy (aPDT) is recognized to be an important strategy to deal with antimicrobial resistance, which is considered nowadays a serious threat to global public health. Although aPDT seems to be a very promising alternative to conventional antimicrobials, there are still important hurdles that currently prevent its implementation in practice. An important aspect to be considered is related with the synthetic access to new cost-effective and efficient photosensitizers (PSs). In this context, the exploitation of the widely available methylene blue (MB) can be a viable and economical option. This dye use is already well established for diagnosis, therapy and also in blood decontamination, which is considered safe. MB presents high binding affinity to multiple microbial targets, that together with its hydrophilicity, rendering it a straightforward PS for aPDT. In this communication, the efficiency of MB in the photoinactivation of bacteria, fungi and viruses will be discussed, first in phosphate buffer solution (PBS) (in vitro) and after in different settings, relevant to clinical and environmental areas: blood, urine, kiwifruit pollen and wastewater (ex vivo). The results show that MB was effective in the photoinactivation of bacteria and viruses in less complex matrices, but not so effective against fungi, when compared with porphyrin derivatives, such as the tetracationic TMPyP. Although the effectiveness of MB decreases with the increase in samples complexity, our studies demonstrate that its photodynamic efficiency can be improved with KI used as adjuvant. The effective reduction of different microorganisms with MB, associated to its safety, provided promising indications towards its safe use, namely in scenarios in which neither commercial PSs nor in-house preparation are available or when large areas need to be treated, as in some environmental applications.