Discovery and Biosynthesis of Imidazolium Antibiotics from the Probiotic Bacillus licheniformis.

Antibiotic resistance is one of the world's most urgent public health problems, and novel antibiotics to kill drug-resistant bacteria are needed. Natural product-derived small molecules have been the major source of new antibiotics. Here we describe a family of antibacterial metabolites isolated from a probiotic bacterium, Bacillus licheniformis. A cross-streaking assay followed by activity-guided isolation yielded a novel antibacterial metabolite, bacillimidazole G, which possesses a rare imidazolium ring in the structure, showing MIC values of 0.7-2.6 µg/mL against human pathogenic Gram-positive and Gram-negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and a lipopolysaccharide (LPS)-lacking Acinetobacter baumannii ΔlpxC. Bacillimidazole G also lowered MICs of colistin, a Gram-negative antibiotic, up to 8-fold against wild-type Escherichia coli MG1655 and A. baumannii. We propose a biosynthetic pathway to the characterized metabolites based on precursor-feeding studies, a chemical biological approach, biomimetic total synthesis, and a biosynthetic gene knockout method.

The frequency and seasonal distribution of viral infection in patients with community-acquired pneumonia and its impact on the prognosis.

BACKGROUND: Studies on the effects of viral coinfection on bacterial pneumonia are still scarce in South Korea. This study investigates the frequency and seasonal distribution of virus infection and its impact on the prognosis in patients with community-acquired pneumonia (CAP). METHODS: The medical records of CAP patients with definite etiology, such as viruses and bacteria, were retrospectively reviewed. Their epidemiologic and clinical characteristics, microbiologic test results, the severity of illness, and 30-day mortality were analyzed. RESULTS: Among 150 study subjects, 68 patients (45.3%) had viral infection alone, 47 (31.3%) had bacterial infection alone, and 35 (23.3%) had viral-bacterial coinfection, respectively. Among 103 patients with viral infections, Influenza A virus (44%) was the most common virus, followed by rhinovirus (19%), influenza B (13%), and adenovirus (6%). The confusion-urea-respiratory rateblood pressure-age of 65 (CURB-65) score of the viral-bacterial coinfection was higher than that of the viral infection (median [interquartile range]: 2.0 [1.0-4.0] vs. 2.0 [0.3-3.0], P=0.029). The 30-day mortality of the viral infection alone group (2.9%) was significantly lower than that of bacterial infection alone (19.1%) and viral-bacterial coinfection (25.7%) groups (Bonferroni-corrected P<0.05). Viral-bacterial coinfection was the stronger predictor of 30-day mortality in CAP (odds ratio [OR], 18.9; 95% confidence interval [CI], 3.0-118.3; P=0.002) than bacterial infection alone (OR, 6.3; 95% CI, 1.1-36.4; P=0.041), compared to viral infection alone on the multivariate analysis. CONCLUSIONS: The etiology of viral infection in CAP is different according to regional characteristics. Viral-bacterial coinfection showed a worse prognosis than bacterial infection alone in patients with CAP.

Interaction of D2 with Ti-adsorbed polyaniline and implication for hydrogen storage.

Interaction of D2 with Ti-adsorbed polyaniline (PANI) and TiO2 at low Ti coverages has been investigated by temperature programmed desorption, Auger electron spectroscopy, and H2-D2 exchange in a high pressure cell. In contrast to recent DFT calculations (Lee et al. Phys. Rev. Lett. 2006, 97, 56104-56107) that have shown a multiple number of molecular hydrogen chemisorption on Ti-decorated PANI, only 0.52 D2 molecules per Ti atomically adsorb on Ti-deposited PANI at 87 K at a nominal Ti coverage of 2 ML. Broad TPD spectra of D2, HD, and H2 were observed, which showed a common peak at 250 K and another isotope-dependent peak at higher temperature. Ti deposited on TiO2 forms clusters with a size distribution at 87 K, on which D2 atomically adsorbs. As the Ti coverage increases, the D2 desorption peak gradually shifts from 200 to 260 K and the number of D2 molecules adsorbed per Ti also increases from 0.26 at 0.1 ML to 0.87 at 2 ML. We attribute this to the fact that D2 adsorbs on larger clusters with a greater adsorption energy. TPD spectra of D2 desorbing from Ti (2 ML)/PANI and Ti (1 ML)/TiO2 look very similar to each other. This led us to conclude that Ti also adsorbs on PANI in clusters. We suggest that no molecular D2 adsorption on Ti/PANI at 87 K is due to a reduced electron backdonation ability of Ti upon clustering. The small number of adsorbed D2 per Ti on both substrates was ascribed to irreversible D2 adsorption only on relatively large Ti clusters, while D2 adsorbs reversibly on small clusters. This was indirectly confirmed by the observation that continuous H2-D2 isotope exchange occurs to produce HD on Ti/PANI as well as on Ti/TiO2 at 106 K in a high pressure cell at 5.7 mTorr. Desorption mechanisms involving H atom abstraction from PANI by Ti clusters are proposed to account for the complex isotope-dependent TPD spectra. Implication of the present results for hydrogen storage based on Ti-dispersed polymers is briefly addressed.

Phenotypic and genotypic analysis of anti-tuberculosis drug resistance in Mycobacterium tuberculosis isolates in Myanmar.

BACKGROUND: Tuberculosis (TB) is one of the most serious health problems in Myanmar. Because TB drug resistance is associated with genetic mutation(s) relevant to responses to each drug, genotypic methods for detecting these mutations have been proposed to overcome the limitations of classic phenotypic drug susceptibility testing (DST). We explored the current estimates of drug-resistant TB and evaluated the usefulness of genotypic DST in Myanmar. METHODS: We determined the drug susceptibility of Mycobacterium tuberculosis isolated from sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB centers in Myanmar during 2013 by using conventional phenotypic DST and the GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were confirmed by sequencing the genes relevant to each type of resistance (rpoB for rifampicin; katG and inhA for isoniazid). RESULTS: Of 191 isolates, phenotypic DST showed that 27.7% (n=53) were resistant to at least one first-line drug and 20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug-resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3% (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were 99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST (kappa=0.99; 95% confidence interval 0.96-1.01). CONCLUSIONS: The results highlight the burden of TB drug resistance and prove the usefulness of the genotypic DST in Myanmar.

Subarachnoid hemorrhage mimicking leakage of contrast media after coronary angiography.

We report a patient who developed subarachnoid hemorrhage (SAH) just after coronary angiography (CAG) with non-ionic contrast media (CM) and minimal dose of heparin. The 55-year-old man had a history of acute ST elevation myocardial infarction that had been treated with primary percutaneous coronary intervention and was admitted for a follow-up CAG. The CAG was performed by the transradial approach, using 1000 U of unfractionated heparin for the luminal coating and 70 mL of iodixanol. At the end of CAG, he complained of nausea and rapidly became stuporous. Brain CT showed a diffusely increased Hounsfield unit (HU) in the cisternal space, similar to leakage of CM. The maximal HU was 65 in the cisternal space. No vascular malformations were detected on cerebral angiography. The patient partially recovered his mental status and motor weakness after 2 days. Two weeks later, subacute SAH was evident on magnetic resonance imaging. The patient was discharged after 28 days.