Across the studies analyzed, findings on survival and phenotypic stability under repeated sub-effective aPDT exposures are compiled in Table 1. The table details the microbial models, inoculum sizes, photosensitizers, illumination parameters, and cycling protocols employed, along with the reported outcomes related to tolerance or resistance development.
Table 1. Overview of studies assessing tolerance and resistance to photodynamic inactivation following multiple cycles of sub-lethal aPDT treatment.
Targeted microorganism(s) | Form(s) | Concentration (CFU/mL) | PS | PS conc. | Dark incubation time (min) | Light Source | Wavelength (nm) | Fluence (J/cm²) | Cycles | Subculture from previous cycles | Tolerance/Resistance | Reference | |
Bacteria | |||||||||||||
| Acinetobacter baumannii | Planktonic | ~ 107 | MB | 12.5 µg/mL | N.C. | Diode laser | 635 | 63 | 15 | 50 µL from treated suspension | No | |
| Actinobacillus actinomycetemcomitans, & Peptostreptococcus micros | Planktonic | 108 | GlamTMPn | 10 µM | 30 min | Incandescent lamps | 400-700 | N.C. | 10 | Surviving colonies from agar plate | No |
|
| Planktonic | 108 | BOHTMPn | 10 µM | 30 min | Incandescent lamps | 400-700 | N.C. | 10 | No | |||
| Escherichia coli & Vibrio fischeri | Planktonic | 107 | Tri-Py+-Me-PF | 5 µM | 10 min | Fluorescent lamps | 380-700 | 64.8 | 10 | Single surviving colony from agar plate | No | |
| E. coli | Planktonic | 108 | HMME | 20 and then 35 µM | 30 min | Halogen lamp | 400-780 | 48 | 20 | Single surviving colony from agar plate | No | |
| E. coli | Planktonic | ~ 106 | ZnPPc4+ | 2 µM | 30 min | Halogen lamp | 380-750 | 9 | 10 | Surviving colonies from agar plate | No | |
| E. coli & Staphylococcus aureus | Planktonic | 106-7 | MB (Periowave™) | ~ 100 µg/mL | N.C. | Non-thermal diode laser PW1100 | 670 | 48 | 11 & 25 | Surviving colonies from agar plate | No | |
| E. coli & S. aureus | Planktonic | ~ 108 | ZnTnHex-2-PyP | 1 µM | N.A. | Overhead projector OHP-3100 p | 400 | Continuous 0.5 mW/cm2 and 44.4 J/cm2 | 10-20 | Treated suspension | No | |
| E. coli & S. aureus | Planktonic | 108 | Zn-TBut4PyP | 0.5 & 1 µg/mL | 10 min | Tungsten lamp | 320-780 | 54 | 10 | Single surviving colony from agar plate | No | |
| E. faecalis | N.C. | N.C. | Ce6 | 21 µM | N.C. | N.C. | 660 | 45
| 4 | Single surviving colony from agar plate | No
| |
| E. faecalis | N.C. | N.C. | MB | 78 µM | N.C. | N.C. | 660 | 80 | 4 | No
| ||
| P. aeruginosa & S. aureus | Planktonic | 108 | MB
| 2.5-25 µg/mL | 30 s 30 min | LED | 635 | 100/200 | 10 | Single surviving colony from agar plate | No | |
| P. aeruginosa & S. aureus | Planktonic | 108 | TMP | 2.5-100 µg/mL | 30 s 30 min | LED | 635 | 100/200 | 10 | No | ||
| P. aeruginosa & S. aureus | Planktonic | 107 | RLP068/Cl | 0.008-13.2 µg/mL | 5 min | Non-coherent halogen lamp | 600-700 | 30 | 20 | 10 µL from treated suspension | No | |
| P. aeruginosa & S. aureus | Planktonic | 105 | [Ru(II)]1 | 5 µM | 20 min | LED | 450-470 nm | 13.38 | 8 | Treated suspension | No | |
| P. aeruginosa & S. aureus | Planktonic | 105 | [Ru(II)]2 | 1 µM | 20 min | LED | 450-470 nm | 13.38 | 8 | No | ||
| S. aureus | Planktonic | 108-9 | Tetra-Py+-Me | 5 µM | 10 min | LED | 380-700 | 14.4 | 10 | Surviving colonies from agar plate | No | |
| S. aureus | Planktonic | 1.75 × 107 | MB | 33 µM | N.C. | fluorescent lamps | 575-700 | 2.4 | 8 | Single surviving colony from agar plate | Yes (after 3 cycles) | |
| S. aureus, Enterococcus faecium & Streptococcus agalactiae | Planktonic | 5 × 107 | RB | 1 µM | 15 min | LED | 515 | 40 | 15 | Treated suspension | Yes (after 5 cycles) | |
| S. agalactiae | Planktonic | 5 × 107 | RB
| 0.08 µM | 15 min | LED | 515 | 20 | 10 | Treated suspension | Yes (after 5 cycles) | |
| Streptococcus pyogenes | Planktonic | 5 × 107-8 | Cur | 2.25 mg/mL | 4 min | LED | 450 | 70.2-71.7 | 10 | Surviving colonies from agar plate | No | |
Fungi |
|
|
|
|
|
|
|
|
|
|
|
| |
| Candida albicans | Planktonic | 105 | RLP068/Cl | 1.3 µg/mL | 5 min | Non-coherent halogen lamp | 600-700 | 30 | 20 | 10 µL from treated suspension | No | |
| C. albicans | Planktonic
| 107 | PDZ | 25 mg/L | 20 min | LED | 660 | 18 | 3 | 30 surviving colonies from agar plate | No | |
| C. albicans | Biofilm | 107 | PDZ | 25 mg/L | 20 min | LED | 660 | 18 | 5 | No
| ||
| C. albicans | Planktonic and biofilm | 107 | PDZ
| 500 mg/L | 20 min | LED | 660 | 18 | 10 | Treated suspension | No
| |
| C. albicans | Planktonic and biofilm | 107 | Cur | 40 µM | 20 min | LED | 660 | 18 | 10 | Yes (after 3 cycles) | ||
Viruses |
|
|
|
|
|
|
|
|
|
|
|
| |
| T4-like bacteriophage | N.A. | ~ 7-8 log PFU/mL | Tri-Py+-Me-PF | 5 µM | 120 min | fluorescent lamps | 380-700 | 28.8 | 10 | Treated suspension | No | |
| MS2, Qβ, MNV-1, & BEV-2 | N.A. | 9.6 log PFU/mL | TMPyP | 0.5 µM | N.C. | LED | 380-780 | 0.96 | 10 | Treated suspension | No | |
Abbreviations: BOHTMPn: 2,7,12,17-tetrakis(2-methoxyethyl)-9-p-carboxybenzyloxyporphycene; Ce6: Chlorin-e6; Cur: Curcumin; GlamTMPn: 2,7,12,17-tetrakis(2-methoxyethyl)-9-glutaramidoporphycene; HMME: hematoporphyrin monomethyl ether; LED: light-emitting diode; MB: methylene blue N.A.: not applicable; N.C.: not communicated; PDZ: Photodithazine®; RB: Rose Bengal; Tetra-Py+-Me: 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin tetra-iodide; TMP: meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate; TMPyP: 5,10,15,20-tetrakis (1methyl-4-pyridinium) porphyrin tetra(p-toluenesulfonate); Tri-Py+-Me: 5,10,15-tris(1methylpyridinium-4-yl)-20-(pentafluorophenyl) porphyrin tri-iodide; Tri-Py+-Me-PF: 5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)-porphyrin triiodide; ZnPPc4+: zinc(II) 2,9,16,23-tetrakis[4-(N-methylpyridyloxy)]phthalocyanine iodide; Zn-TBut4PyP: Zn-mesotetra-[4-N-(2′-butyl) pyridyl]porphyrin; ZnTnHex-2-PyP : Zn(II) mesotetrakis(N-n-hexylpyridinium-2-yl) porphyrin; [Ru(II)]1: [Ru(Phen)3]2+ (PF6-)2; [Ru(II)]2: [Ru(Phen)2(Phen-T-Fluorenyl)]2+ (Cl-)2. | |||||||||||||