A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputum
ABSTRACT Early bactericidal activity is a vital measure in developing new tuberculosis (TB) drugs. Traditional methods, including colony-forming units (CFUs) and time to positivity (TTP), have limitations. This study aimed to evaluate the efficacy of TPAPy-Tre fluorescence microscopy in monitoring e...
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| Language: | English |
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American Society for Microbiology
2025-07-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02457-24 |
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| author | Mengru Yang Guiqin Dai Dan Li Pengfei Zhao Senlin Zhan Hongjuan Qin Hongzhou Lu Mingbin Zheng Peize Zhang |
| author_facet | Mengru Yang Guiqin Dai Dan Li Pengfei Zhao Senlin Zhan Hongjuan Qin Hongzhou Lu Mingbin Zheng Peize Zhang |
| author_sort | Mengru Yang |
| collection | DOAJ |
| description | ABSTRACT Early bactericidal activity is a vital measure in developing new tuberculosis (TB) drugs. Traditional methods, including colony-forming units (CFUs) and time to positivity (TTP), have limitations. This study aimed to evaluate the efficacy of TPAPy-Tre fluorescence microscopy in monitoring early therapeutic responses compared with conventional culture methods in patients with pulmonary multidrug-resistant/rifampicin-resistant TB. In an open-label clinical trial at the Third People’s Hospital of Shenzhen, China, seven sputum smear-positive patients aged ≥18 years were enrolled. Sputum samples were consecutively analyzed using solid and liquid cultures and TPAPy-Tre microscopy. The study found that TPAPy-Tre fluorescence intensity significantly decreased from 271.5 (95% confidence interval [CI], 177.4–365.7) before treatment to 142.8 (95% CI, 104.7–180.9) after treatment (P < 0.05). TPAPy-Tre results strongly correlated with CFU (Spearman ρ = 0.60; 95% CI, 0.35–0.77; P < 0.001) and TTP (Spearman ρ = −0.33; 95% CI, −0.56 to −0.04; P < 0.05). Among selected participants, the median fluorescence intensity decreased from 51.5 (interquartile range [IQR], 39.0–63.6) to 13.2 (IQR, 7.8–20.0) after treatment (P < 0.001). TPAPy-Tre shows potential as a rapid, visual method for tracking bacterial vitality during TB treatment, offering immediate feedback on treatment response. These results support its use alongside conventional methods in clinical settings, though larger studies are needed for further validation.IMPORTANCEEarly bactericidal activity (EBA) is an important tool in clinical studies in the development of new tuberculosis drugs. Current traditional methods of efficacy monitoring present significant limitations. There is a need for novel and efficient tools to monitor treatment response in real-time when EBA is performing. |
| format | Article |
| id | doaj-art-df4adbbb3b894ab8be4464946d408f16 |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-df4adbbb3b894ab8be4464946d408f162025-08-20T03:28:22ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-07-0113710.1128/spectrum.02457-24A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputumMengru Yang0Guiqin Dai1Dan Li2Pengfei Zhao3Senlin Zhan4Hongjuan Qin5Hongzhou Lu6Mingbin Zheng7Peize Zhang8School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, ChinaInstitute of Hepatology, National Clinical Research Center for Infectious Diseases, Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, ChinaNational Clinical Research Center for Infectious Diseases, Shenzhen Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Shenzhen, Guangdong, ChinaInstitute of Hepatology, National Clinical Research Center for Infectious Diseases, Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, ChinaDepartment of Pulmonary Medicine and Tuberculosis, Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, ChinaDepartment of Pulmonary Medicine and Tuberculosis, Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, ChinaDepartment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, ChinaShenzhen Clinical Research Center for Tuberculosis, Shenzhen, ChinaSchool of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, ChinaABSTRACT Early bactericidal activity is a vital measure in developing new tuberculosis (TB) drugs. Traditional methods, including colony-forming units (CFUs) and time to positivity (TTP), have limitations. This study aimed to evaluate the efficacy of TPAPy-Tre fluorescence microscopy in monitoring early therapeutic responses compared with conventional culture methods in patients with pulmonary multidrug-resistant/rifampicin-resistant TB. In an open-label clinical trial at the Third People’s Hospital of Shenzhen, China, seven sputum smear-positive patients aged ≥18 years were enrolled. Sputum samples were consecutively analyzed using solid and liquid cultures and TPAPy-Tre microscopy. The study found that TPAPy-Tre fluorescence intensity significantly decreased from 271.5 (95% confidence interval [CI], 177.4–365.7) before treatment to 142.8 (95% CI, 104.7–180.9) after treatment (P < 0.05). TPAPy-Tre results strongly correlated with CFU (Spearman ρ = 0.60; 95% CI, 0.35–0.77; P < 0.001) and TTP (Spearman ρ = −0.33; 95% CI, −0.56 to −0.04; P < 0.05). Among selected participants, the median fluorescence intensity decreased from 51.5 (interquartile range [IQR], 39.0–63.6) to 13.2 (IQR, 7.8–20.0) after treatment (P < 0.001). TPAPy-Tre shows potential as a rapid, visual method for tracking bacterial vitality during TB treatment, offering immediate feedback on treatment response. These results support its use alongside conventional methods in clinical settings, though larger studies are needed for further validation.IMPORTANCEEarly bactericidal activity (EBA) is an important tool in clinical studies in the development of new tuberculosis drugs. Current traditional methods of efficacy monitoring present significant limitations. There is a need for novel and efficient tools to monitor treatment response in real-time when EBA is performing.https://journals.asm.org/doi/10.1128/spectrum.02457-24early bactericidal activity (EBA)tuberculosis (TB)TPAPy-Tre microscopyfluorescence intensitytreatment response monitoring |
| spellingShingle | Mengru Yang Guiqin Dai Dan Li Pengfei Zhao Senlin Zhan Hongjuan Qin Hongzhou Lu Mingbin Zheng Peize Zhang A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputum Microbiology Spectrum early bactericidal activity (EBA) tuberculosis (TB) TPAPy-Tre microscopy fluorescence intensity treatment response monitoring |
| title | A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputum |
| title_full | A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputum |
| title_fullStr | A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputum |
| title_full_unstemmed | A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputum |
| title_short | A cytoderm metabolic labeling TPAPy-Tre for real-time detection of vitality of Mycobacterium tuberculosis in sputum |
| title_sort | cytoderm metabolic labeling tpapy tre for real time detection of vitality of mycobacterium tuberculosis in sputum |
| topic | early bactericidal activity (EBA) tuberculosis (TB) TPAPy-Tre microscopy fluorescence intensity treatment response monitoring |
| url | https://journals.asm.org/doi/10.1128/spectrum.02457-24 |
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