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Abstract:The high incidence of Mycobacterium infection, notably multidrug-resistant M. tuberculosis infection, has become a significant public health concern worldwide. In this study, we isolate and analyze a mycobacteriophage, BTCU-1, and a foundational study was performed to evaluate the antimycobacterial activity of BTCU-1 and its cloned lytic endolysins. Using Mycobacterium smegmatis as host, a mycobacteriophage, BTCU-1, was isolated from soil in eastern Taiwan. The electron microscopy images revealed that BTCU-1 displayed morphology resembling the Siphoviridae family. In the genome of BTCU-1, two putative lytic genes, BTCU-1_ORF7 and BTCU-1_ORF8 (termed lysA and lysB, respectively), were identified, and further subcloned and expressed in Escherichia coli. When applied exogenously, both LysA and LysB were active against M. smegmatis tested. Scanning electron microscopy revealed that LysA and LysB caused a remarkable modification of the cell shape of M. smegmatis. Intracellular bactericidal activity assay showed that treatment of M. smegmatis- OPEN ACCESSMolecules 2015, 20 19278 infected RAW 264.7 macrophages with LysA or LysB resulted in a significant reduction in the number of viable intracellular bacilli. These results indicate that the endolysins derived from BTCU-1 have antimycobacterial activity, and suggest that they are good candidates for therapeutic/disinfectant agents to control mycobacterial infections.

The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1-7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥ 7 days) of symptoms, a history of night sweats, lack of fever (> 38 °C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB.

BackgroundIn contrast to the conventional model of hospital-treated and government directly observed treatment (DOT) for multidrug-resistant tuberculosis (MDR-TB) patient care, the Taiwan MDR-TB Consortium (TMTC) was launched in May 2007 with the collaboration of five medical care groups that have provided both care and DOT. This study aimed to determine whether the TMTC provided a better care model for MDR-TB patients than the conventional model.Methods and FindingsA total of 651 pulmonary MDR-TB patients that were diagnosed nation-wide from January 2000-August 2008 were enrolled. Of those, 290 (45%) MDR-TB patients whose initial sputum sample was taken in January 2007 or later were classified as patients in the TMTC era. All others were classified as patients in the pre-TMTC era. The treatment success rate at 36 months was better in the TMTC era group (82%) than in the pre-TMTC era group (61%) (p<0.001). With multiple logistic regressions, diagnosis in the TMTC era (adjusted odds ratio (aOR) 2.8, 95% confidence interval (CI) 1.9–4.2) was an independent predictor of a higher treatment success rate at 36 months. With the time-dependent proportional hazards method, a higher treatment success rate was still observed in the TMTC era group compared to the pre-TMTC era group (adjusted hazard ratio 6.3, 95% CI 4.2–9.5).ConclusionThe improved treatment success observed in the TMTC era compared to the pre-TMTC era is encouraging. The detailed TMTC components that contribute the most to the improved outcome will need confirmation in follow-up studies with large numbers of MDR-TB patients.

Routinely used molecular diagnostic methods for mycobacterium identification are expensive and time-consuming. To tackle this problem, we develop a method to streamline identification of Mycobacterium tuberculosis complex (MTBC) in broth culture media by using detonation nanodiamonds (DNDs) as a platform to effectively capture the antigen secreted by MTBC which is cultured in BACTEC MGIT 960, followed by the analysis of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS). The 5 nm DNDs can capture the MTBC secretory antigen without albumin interference. With on diamond digestion, we confirm the DND captured antigen is cell filtrate protein 10 (CFP-10) because its Mascot analysis shows a score of 68. The dot blotting method further verifies a positive reaction with anti-CFP-10, indicating that CFP-10 is secreted in the medium of mycobacterium growth indicator tube (MGIT) and captured by DNDs. The minimal CFP-10 protein detection limit was 0.09 μg/mL. Furthermore, our approach can avoid the false-positive identification of MTBC by immunological methods due to cross-reactivity. Five hundred consecutive clinical specimens subjected to routine mycobacteria identification in hospital were used in this study, and the sensitivity of our method is 100% and the specificity is 98%. The analysis of each MTBC sample from culture solution can be finished within 1 h and thus shortens the turnaround time of MTBC identification of gold standard culture methods. In sum, DND MALDI-TOF MS for the detection of MTBC is rapid, specific, safe, reliable, and inexpensive.

Cigarette smoking was a more important risk factor for stroke and cerebral infarction than excessive drinking of alcohol.

Genetic variation in NRAMP 1 may affect susceptibility to and increase risk for tuberculosis in Taiwanese aboriginals. Although environmental factors play an important role in tuberculosis infection, genetic factors such as NRAMP 1 polymorphism may also contribute to the high prevalence of tuberculosis in Taiwanese aboriginals.