Mixed Infection of <i>Mycobacterium abscessus subsp. abscessus</i> and <i>Mycobacterium tuberculosis</i> in the Lung

Sohn, Sungmin; Wang, Sungho; Shi, Hyejin; Park, Sungrock; Lee, Sangki; Park, Kyoung Taek

doi:10.5090/kjtcs.2017.50.1.50

Cited by 4 publications

(3 citation statements)

References 8 publications

(15 reference statements)

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“…Additionally, patients suffering from cystic fibrosis or other immunosuppressive condition can be infected by different mycobacteria at the same time. In fact, co-infections with M. abscessus and M. tuberculosis have been reported [27, 28]. The strong bactericidal effect of FP-11g against M. smegmatis supports investigation of this compound and its derivatives for its potential use as a broad antimycobacterial agent.…”

Section: Discussionmentioning

confidence: 96%

Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound

Garcia

Annamalai

Wang

et al. 2018

Preprint

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24We have previously reported the inhibition of bacterial topoisomerase I activity by a 25 fluoroquinophenoxazine compound (FP-11g) with a 6-bipiperidinyl lipophilic side chain that 26 exhibited promising antituberculosis activity (MIC = 2.5 µM against Mycobacterium 27 tuberculosis, SI = 9.8). Here, we found that the compound is bactericidal towards 28Mycobacterium smegmatis, resulting in greater than 5 Log10 reduction in colony-forming units 29[cfu]/mL following a 10 h incubation at 1.25 µM (4X MIC) concentration. Growth inhibition 30 (MIC = 50 µM) and reduction in cfu could also be observed against a clinical isolate of 31 Mycobacterium abscessus. Stepwise isolation of resistant mutants of M. smegmatis was 32 conducted to explore the mechanism of resistance. Mutations in the resistant isolates were 33 identified by direct comparison of whole-genome sequencing data from mutant and wild-type 34 isolates. These include mutations in genes likely to affect the entry and retention of the 35 compound. FP-11g inhibits Mtb topoisomerase I and Mtb gyrase with IC50 of 0.24 and 31.5 µM, 36 respectively. Biophysical analysis showed that FP-11g binds DNA as an intercalator but the IC50 37 for inhibition of Mtb topoisomerase I activity is >10 fold lower than the compound 38 concentrations required for producing negatively supercoiled DNA during ligation of nicked 39 circular DNA. Thus, the DNA-binding property of FP-11g may contribute to its 40 antimycobacterial mechanism, but that alone cannot account for the observed inhibition of Mtb 41 topoisomerase I. 42 43 157 Enzyme assays 158

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Section: Discussionmentioning

confidence: 96%

Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound

Garcia

Annamalai

Wang

et al. 2018

Preprint

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“…abscessus and M . tuberculosis have been reported [34, 35]. The strong bactericidal effect of FP-11g against M .…”

Section: Discussionmentioning

confidence: 99%

Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound

et al. 2019

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We have previously reported the inhibition of bacterial topoisomerase I activity by a fluoroquinophenoxazine compound (FP-11g) with a 6-bipiperidinyl lipophilic side chain that exhibited promising antituberculosis activity (MIC = 2.5 μM against Mycobacterium tuberculosis , SI = 9.8). Here, we found that the compound is bactericidal towards Mycobacterium smegmatis , resulting in greater than 5 Log 10 reduction in colony-forming units [cfu]/mL following a 10 h incubation at 1.25 μM (4X MIC) concentration. Growth inhibition (MIC = 50 μM) and reduction in cfu could also be observed against a clinical isolate of Mycobacterium abscessus . Stepwise isolation of resistant mutants of M . smegmatis was conducted to explore the mechanism of resistance. Mutations in the resistant isolates were identified by direct comparison of whole-genome sequencing data from mutant and wild-type isolates. These include mutations in genes likely to affect the entry and retention of the compound. FP-11g inhibits Mtb topoisomerase I and Mtb gyrase with IC 50 of 0.24 and 27 μM, respectively. Biophysical analysis showed that FP-11g binds DNA as an intercalator but the IC 50 for inhibition of Mtb topoisomerase I activity is >10 fold lower than the compound concentrations required for producing negatively supercoiled DNA during ligation of nicked circular DNA. Thus, the DNA-binding property of FP-11g may contribute to its antimycobacterial mechanism, but that alone cannot account for the observed inhibition of M tb topoisomerase I.

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“…The challenges of managing MTBC and M. avium complex (MAC) co-infection are well described, including the risk for falsely interpreted Xpert RIF (rifampin) results (1,2). MTBC and M. abscessus co-infection has been described in case reports only (3,4). We describe co-infection with 4 species of mycobacteria.…”

mentioning

confidence: 92%

Co-Infection with 4 Species of Mycobacteria Identified by Using Next-Generation Sequencing

Wang¹,

Liu²,

Yung³

et al. 2021

Emerg. Infect. Dis.

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Mixed Infection of Mycobacterium abscessus subsp. abscessus and Mycobacterium tuberculosis in the Lung

Cited by 4 publications

References 8 publications

Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound

Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound

Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound

Co-Infection with 4 Species of Mycobacteria Identified by Using Next-Generation Sequencing

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