title: Inactivation of multidrug resistant (MDR)- and extensively drug resistant (XDR)-Mycobacterium tuberculosis by photodynamic therapy.
abstract: We investigated the effects of photodynamic therapy (PDT) on anti-tuberculosis (TB) activity by measuring inactivation rates, expressed as D-value, of MDR- and XDR-Mycobacterium tuberculosis (M. tb) clinical strains in vitro. Approximately 10(6) colony forming unit per milliliter (CFU/ml) of the bacilli were irradiated with various doses of laser light after exposure to photosensitizers. Survival of M. tb was measured by enumerating CFU in 7H10 medium to measure D-values. No inactivation of M. tb was observed when exposed to photosensitizers (radachlorin or DH-I-180-3) only or laser light only (P>0.1). Treatment with a combination of photosentizer and laser inactivated M. tb although there was a significant difference between the types of photosensitizers applied (P<0.05). Linear inactivation curves for the clinical M. tb strains were obtained up to laser doses of 30 J/cm(2) but prolonged irradiation did not linearly inactivate M. tb, yielding sigmoid PDT inactivation curves. D-values of M. tb determined from the slope of linear regression lines in PDT were not significantly different and ranged from 10.50 to 12.13 J/cm(2) with 670 nm laser irradiation at 100 mW/cm(2) of the fluency rate, except for a drug-susceptible strain among the clinical strains tested. This suggests that PDT inactivated M. tb clinical strains regardless of drug resistance levels of the bacilli. Intermittent and repeated PDT allowed acceleration of the inactivation of the bacilli as a way to avoid the sigmoid inactivation curves. In conclusion, PDT could be alternative as a new option for treatment for MDR- and XDR-tuberculosis.
authors.affiliation: Clinical Research Center, National Masan Tuberculosis Hospital, Gyeongnam, Republic of Korea.
authors.forename: Nackmoon
authors.initials: N
authors.lastname: Sung
authors.forename: Sunmi
authors.initials: S
authors.lastname: Back
authors.forename: Jinhee
authors.initials: J
authors.lastname: Jung
authors.forename: Ki-Hong
authors.initials: KH
authors.lastname: Kim
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Yongjoon
authors.initials: Y
authors.lastname: Ra
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Yang
authors.forename: Cheong
authors.initials: C
authors.lastname: Lim
authors.forename: Sukki
authors.initials: S
authors.lastname: Cho
authors.forename: Kwhanmien
authors.initials: K
authors.lastname: Kim
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Jheon
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011166:Porphyrins / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: C000607508:DH-I-180-3; D017319:Photosensitizing Agents; D011166:Porphyrins; D002734:Chlorophyll; C006969:chlorin
keywords: D-value; MDR-TB; PDT; XDR-TB