Can microbial cells develop resistance to oxidative stress in antimicrobial photodynamic inactivation?

Abstract

Infections have been a major cause of disease throughout the history of humans on earth. With the introduction of antibiotics, it was thought that infections had been conquered. However, bacteria have been able to develop resistance to antibiotics at an exponentially increasing rate. The growing threat from multi-drug resistant organisms calls for intensive action to prevent the emergence of totally resistant and untreatable infections. Novel, non-invasive, non-antibiotic strategies are needed that act more efficiently and faster than current antibiotics. One promising alternative is antimicrobial photodynamic inactivation (APDI), an approach that produces reactive oxygen species when dyes and light are combined. So far, it has been questionable if bacteria can develop resistance against APDI. This review paper gives an overview of recent studies concerning the susceptibility of bacteria towards oxidative stress, and suggests possible mechanisms of the development of APDI-resistance that should at least be addressed. Some ways to potentiate APDI and also to overcome future resistance are suggested.

Keywords: Antimicrobial photodynamic inactivation; Oxidative stress; Oxidative stress response; Resistance to APDI; Sub-lethal APDI.

Figure 1

Antibiotic resistance mechanisms in bacteria

Figure 2

Principals of Antimicrobial Photodynamic Inactivation shown in a Jablonski Diagram

Figure 3

Activation of redox-sensitive transcriptional regulators in Escherichia coli.

Figure 4

Schematic illustration of the main types of bacterial drug efflux pumps (MFS: major facilitator superfamily, SMR: small multi drug resistance, MATE: multi drug and toxic compound extrusion, ABC: ATP-binding cassette family, and RND: resistance-nodulation-division family)

Figure 5

Stages of biofilm development

Figure 6

Mechanisms of reduced antimicrobial susceptibility of bacteria in biofilm (1-Antimicrobial agents kill susceptible outer cells, 2- Inner persister cells survive, 3- Entire biofilm regenerates)