Background: Due to increased bacterial multi-drug resistance (MDR), there is an antibiotic depletion to treat infectious diseases. Consequently, other promising options have emerged, such as the antimicrobial photodynamic inactivation therapy (aPDI) based on photosensitizer (PS) compounds to produce light-activated local oxidative stress (photooxidative stress). However, there are scarce studies regarding the mode of action of PS compounds to induce photooxidative stress on pathogenic γ-proteobacteria such as MDR-Klebsiella pneumoniae.
Methodology: The mode of action exerted by the cationic Ir(III)-based PS (PSIR-3) to inhibit the growth of K. pneumoniae was analyzed. RT-qPCR determined the transcriptional response induced by PSIR-3 on bacteria treated with aPDI. The expression levels of genes associated with a bacterial oxidative response, such as oxyR and sodA, and the extracytoplasmic, regulators rpoE and hfq were determined. Also, were determined the transcriptional response of the extracytoplasmic factors mrkD, acrB, magA, and rmpA.
Results: At 17 μW/cm2 photon flux and 4 μg/mL of the PSIR-3 compound, the K. pneumoniae growth was inhibited in 3 log10. Compared with untreated bacteria, the transcriptional response induced by PSIR-3 occurs via the extracytoplasmic sigma factor rpoE and hfq. In contrast, no participation in the oxyR pathway or induction of the sodA gene was observed. This response was accompanied by the upregulation of the extracytoplasmic virulence factors mrkD, magA, and rmpA.
Conclusions: PDI aPDI produced by PSIR-3 kills K. pneumoniae and may induce damage to the bacterial envelope. The bacterium tries to avoid this injury by activation of extracytoplasmic factors mediated through the rpoE regulon.
Keywords: Antibiotic resistance; Antimicrobial photodynamic therapy; Klebsiella pneumoniae; Photodynamic treatment; rpoE regulon.
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