Management of Endophthalmitis with and without Topical Antibiotics: A Case-Control Study.

PURPOSE: The aim of this study was to compare the management outcome of endophthalmitis with and without the use of topical antibiotics. METHODS: A retrospective comparative chart review of 2 cohorts of endophthalmitis (other than those associated with open-globe injury, keratitis, or wound site infection), one managed with topical antibiotics (TA group) and one without (NTA group), was performed. RESULTS: The study included a total of 270 eyes of 270 patients. Of these, 169 eyes were in the TA group and 101 were in the NTA group. Post-cataract surgery was the most common etiology, accounting for 81.06 and 78.2% of cases, respectively (p = 0.57). A favorable functional outcome at the last visit was seen in 37.5 and 39.6% of eyes (p = 0.73), and a favorable anatomic outcome was noted in 61.2 and 49.5% of eyes (p = 0.06), respectively. The median follow-up was 3.5 and 9 months, respectively (p < 0.0001). Susceptibilities to the common antibiotics used (vancomycin, ceftazidime, and amikacin) were comparable, with the exception of imipenem, for which the susceptibility noted was 95 and 66%, respectively (p = 0.01). Culture positivity in the TA group was seen in 72 out of 169 eyes (42.6%), while in the NTA group it was seen in 98 out of 101 eyes (97.02%; p < 0.0001). CONCLUSION: Topical antibiotics do not give any added advantage in the management of endophthalmitis otherwise being treated with intravitreal antibiotics and standard vitrectomy techniques.

R-type bacteriocins of Xenorhabdus bovienii determine the outcome of interspecies competition in a natural host environment.

Xenorhabdus species are bacterial symbionts of Steinernema nematodes and pathogens of susceptible insects. Different species of Steinernema nematodes carrying specific species of Xenorhabdus can invade the same insect, thereby setting up competition for nutrients within the insect environment. While Xenorhabdus species produce both diverse antibiotic compounds and prophage-derived R-type bacteriocins (xenorhabdicins), the functions of these molecules during competition in a host are not well understood. Xenorhabdus bovienii (Xb-Sj), the symbiont of Steinernema jollieti, possesses a remnant P2-like phage tail cluster, xbp1, that encodes genes for xenorhabdicin production. We show that inactivation of either tail sheath (xbpS1) or tail fibre (xbpH1) genes eliminated xenorhabdicin production. Preparations of Xb-Sj xenorhabdicin displayed a narrow spectrum of activity towards other Xenorhabdus and Photorhabdus species. One species, Xenorhabdus szentirmaii (Xsz-Sr), was highly sensitive to Xb-Sj xenorhabdicin but did not produce xenorhabdicin that was active against Xb-Sj. Instead, Xsz-Sr produced high-level antibiotic activity against Xb-Sj when grown in complex medium and lower levels when grown in defined medium (Grace's medium). Conversely, Xb-Sj did not produce detectable levels of antibiotic activity against Xsz-Sr. To study the relative contributions of Xb-Sj xenorhabdicin and Xsz-Sr antibiotics in interspecies competition in which the respective Xenorhabdus species produce antagonistic activities against each other, we co-inoculated cultures with both Xenorhabdus species. In both types of media Xsz-Sr outcompeted Xb-Sj, suggesting that antibiotics produced by Xsz-Sr determined the outcome of the competition. In contrast, Xb-Sj outcompeted Xsz-Sr in competitions performed by co-injection in the insect Manduca sexta, while in competition with the xenorhabdicin-deficient strain (Xb-Sj:S1), Xsz-Sr was dominant. Thus, xenorhabdicin was required for Xb-Sj to outcompete Xsz-Sr in a natural host environment. These results highlight the importance of studying the role of antagonistic compounds under natural biological conditions.

In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation.

Sortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as Staphylococcus aureus. As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable target for the enhancement of novel anti-infective drugs that aim to interfere with key bacterial virulence mechanisms, such as biofilm formation, without developing drug resistance. Here, we used virtual screening to search an in-house natural compound library and identified two natural compounds, N1287 (Skyrin) and N2576 ((4,5-dichloro-1H-pyrrol-2-yl)-[2,4-dihydroxy-3-(4-methyl-pentyl)-phenyl]-methanone) that inhibited the enzymatic activity of SrtA. These compounds also significantly reduced the growth of S. aureus but possessed moderate mammalian toxicity. Furthermore, S. aureus strains treated with these compounds exhibited reduction in adherence to host fibrinogen, as well as biofilm formation. Hence, these compounds may represent an anti-infective therapy without the side effects of antibiotics.

WITHDRAWN:Supplementation of L-Threonine for Optimization of Dietary Crude Protein Levels in Broilers.

Ahead of Print article withdrawn by publisher.

Antitubercular Nanocarrier Combination Therapy: Formulation Strategies and in Vitro Efficacy for Rifampicin and SQ641.

Tuberculosis (TB) remains a major global health concern, and new therapies are needed to overcome the problems associated with dosing frequency, patient compliance, and drug resistance. To reduce side effects associated with systemic drug distribution and improve drug concentration at the target site, stable therapeutic nanocarriers (NCs) were prepared and evaluated for efficacy in vitro in Mycobacterium tuberculosis-infected macrophages. Rifampicin (RIF), a current, broad-spectrum antibiotic used in TB therapy, was conjugated by degradable ester bonds to form hydrophobic prodrugs. NCs encapsulating various ratios of nonconjugated RIF and the prodrugs showed the potential ability to rapidly deliver and knockdown intracellular M. tuberculosis by nonconjugated RIF and to obtain sustained release of RIF by hydrolysis of the RIF prodrug. NCs of the novel antibiotic SQ641 and a combination NC with cyclosporine A were formed by flash nanoprecipitation. Delivery of SQ641 in NC form resulted in significantly improved activity compared to that of the free drug against intracellular M. tuberculosis. A NC formulation with a three-compound combination of SQ641, cyclosporine A, and vitamin E inhibited intracellular replication of M. tuberculosis significantly better than SQ641 alone or isoniazid, a current first-line anti-TB drug.

Permeability enhancing lipid-based co-solvent and SEDDS formulations of SQ641, an antimycobacterial agent.

CONTEXT: Tuberculosis (TB) is a common and often deadly infectious disease caused by strains of Mycobacteria. Development of new anti-tubercular drugs is essential to control the emergence and severity of multidrug-resistant TB. OBJECTIVE: The objective of this study was to develop an oral preclinical liquid formulation of SQ641 and to determine the permeability across rat intestinal tissue by Ussing chamber. METHODS: Thermal and chemical characterization of SQ641 was performed by differential scanning calorimetric analysis, thermogravimetric analysis and high performance liquid chromatography. A high throughput solubility screening technique was utilized to determine the solubility of SQ641 in different solvents and co-solvents. Several co-solvent and self-emulsifying drug delivery system (SEDDS) formulations were selected for Ussing chamber permeability studies. RESULTS AND DISCUSSION: Calculated average apparent permeability coefficients of SEDDS formulations of SQ641 (ranging from 0.03 × 10(-6) to 0.33 × 10(-6)) were found to be higher than the permeability coefficients of co-solvent formulations (ranging from 0.00 × 10(-6) to 0.09 × 10(-6)) and those of the neat drug SQ641 in buffer (0.00 × 10(-6)). CONCLUSION: SEDDS formulations with superior permeability characteristics may provide a useful dosage form for oral intake of anti-tubercular drug SQ641, possibly due to the increase in solubility and immediate dispersion of drug.

Therapeutic efficacy of SQ641-NE against Mycobacterium tuberculosis.

A phospholipid-based nanoemulsion formulation of SQ641 (SQ641-NE) was active against intracellular Mycobacterium tuberculosis in J774A.1 mouse macrophages, although SQ641 by itself was not. Intravenous (i.v.) SQ641-NE was cleared from circulation and reached peak concentrations in lung and spleen in 1 h. In a murine tuberculosis (TB) model, 8 i.v. doses of SQ641-NE at 100 mg/kg of body weight over 4 weeks caused a 1.73 log10 CFU reduction of M. tuberculosis in spleen and were generally bacteriostatic in lungs.

Exploring the Prevalence, Predictors, and Impact of Bacterial Infections to Guide Empiric Antimicrobial Decisions in Cirrhosis (EPIC-AD).

Background/Aims: This study delved into cirrhosis-related infections to unveil their epidemiology, risk factors, and implications for antimicrobial decisions. Methods: We analyzed acutely decompensated cirrhosis patients (n = 971) from North India between 2013-2023 at a tertiary center. Microbiological and clinical features based on infection sites (EASL criteria) and patient outcomes were assessed. Results: Median age was 45 years; 87% were males with 47% having alcoholic hepatitis. Of these, 675 (69.5%) had infections; 305 (45%) were culture-confirmed. Notably, 71% of confirmed cases were multi-drug resistant organisms (MDRO)-related, chiefly carbapenem-resistant (48%). MDRO prevalence was highest in pulmonary (80.5%) and skin-soft-tissue infections (76.5%). Site-specific distribution and antimicrobials were suggested. Predictive models identified prior hospitalization [OR:2.23 (CI:1.58-3.14)], norfloxacin prophylaxis [OR:2.26 (CI:1.44-3.55)], prior broad-spectrum antibiotic exposure [OR:1.61 (CI:1.12-2.30)], presence of systemic inflammatory response-SIRS [OR:1.75 (CI: 1.23-2.47)], procalcitonin [OR:4.64 (CI:3.36-6.40)], and HE grade [OR:1.41 (CI:1.04-1.90)], with an area under curve; AUC of 0.891 for infection prediction. For MDRO infection prediction, second infection [OR: 7.19 (CI: 4.11-12.56)], norfloxacin prophylaxis [OR: 2.76 (CI: 1.84-4.13)], CLIF-C OF [OR: 1.10 (CI: 1.01-1.20)], prior broad-spectrum antibiotic exposure [OR: 1.66 (CI: 1.07-2.55)], rifaximin [OR: 040 (0.22-0.74)] multisite [OR: 3.67 (CI: 1.07-12.56)], and polymicrobial infection [OR: 4.55 (CI: 1.45-14.17)] yielded an AUC of 0.779 and 93% specificity. Norfloxacin prophylaxis, multisite infection, mechanical ventilation, prior broad-spectrum antibiotic exposure, and infection as acute precipitant predicted carbapenem-resistant infection (AUC: 0.821). Infections (culture-proven or probable), MDROs, carbapenem/pan-drug resistance, and second infections independently linked with mortality (P < 0.001), adjusted for age, leucocytosis, and organ failures. A model incorporating age [HR:1.02 (CI: 1.01-1.03), infection [HR:1.52 (CI: 1.05-2.20)], prior hospitalization [HR:5.33 (CI: 3.75-7.57)], norfloxacin [HR:1.29 (CI: 1.01-1.65)], multisite infection [HR:1.47 (CI:1.06-2.04)], and chronic liver failure consortium-organ failure score; CLIF-C OF [HR:1.17 (CI: 1.11-1.23)] predicted mortality with C-statistics of 0.782 (P < 0.05). Conclusion: High MDRO burden, especially carbapenem-resistant, necessitates urgent control measures in cirrhosis. Site-specific epidemiology and risk models can guide empirical antimicrobial choices in cirrhosis management.

SQ109 and PNU-100480 interact to kill Mycobacterium tuberculosis in vitro.

OBJECTIVES: To investigate in vitro interaction between two compounds, SQ109 and PNU-100480, currently in development for the treatment of Mycobacterium tuberculosis (MTB). METHODS: The two-drug interactions between SQ109 and PNU-100480 and its major metabolite PNU-101603 were assessed by chequerboard titration, and the rate of killing and intracellular activity were determined in both J774A.1 mouse macrophages and whole blood culture. RESULTS: In chequerboard titration, interactions between SQ109 and either oxazolidinone were additive. In time-kill studies, SQ109 killed MTB faster than PNU compounds, and its rate of killing was further enhanced by both oxazolidinones. The order of efficacy of single compounds against intracellular MTB was SQ109 > PNU-100480 > PNU-101603. At sub-MIC, combinations of SQ109 + PNU compounds showed improved intracellular activity over individual drugs; at ≥MIC, the order of efficacy was SQ109 > SQ109 + PNU-100480 > SQ109 + PNU-101603. In whole blood culture, the combined bactericidal activities of SQ109 and PNU-100480 and its major metabolite against intracellular M. tuberculosis did not differ significantly from the sum of the compounds tested individually. CONCLUSIONS: SQ109 and PNU combinations were additive and improved the rate of MTB killing over individual drugs. These data suggest that the drugs may work together cooperatively to eliminate MTB in vivo.

Genotypic variation in root architectural traits under contrasting phosphorus levels in Mediterranean and Indian origin lentil genotypes.

The development of phosphorus-efficient crop cultivars boosts productivity while lowering eutrophication in the environment. It is feasible to improve the efficiency of phosphorus (P) absorption in lentils by enhancing phosphorus absorption through root architectural traits. The root architectural traits of 110 diverse lentil genotypes of Indian and Mediterranean origin were assessed, and the relationships between traits were investigated. In a hydroponics experiment, the lentil lines were examined at the seedling stage under two conditions: adequate P supply and deficient P supply. The Pearson correlation coefficients between root architectural traits and genetic diversity among lentil lines were assessed. To estimate variance components, a model (fixed factor) was used. In this experiment, both phosphorus (P) and genotype were fixed variables. Our lentil lines showed significant genetic variability and considerable genetic diversity for all traits under both treatments. The TRL (total root length) and PRL (primary root length) showed strong positive associations with all other characteristics excluding root average diameter (RAD) in both P treatments. In both P treatments, the RAD revealed a negative significant association with Total Root Tips (TRT), as well as total root volume (TRV) and total root forks (TRF) in the deficit conditions of P. Total root volume (TRV), total surface area (TSA), and total root tips had higher coefficient variance values. The first two principal components represented 67.88% and 66.19% of the overall variance in the adequate and deficit P treatments respectively. The Shannon-Weaver diversity index (H') revealed that RAD, PRL, and TSA had more variability than TRT and TRF under both treatments. According to the Comprehensive Phosphorus Efficiency Measure (CPEM), the best five highly efficient genotypes are PLL 18-09, PLS 18-01, PLL 18-25, PLS 18-23, and PLL 18-07, while IG112131, P560206, IG334, L11-231, and PLS18-67 are highly inefficient genotypes. The above contrasting diverse lentil genotypes can be utilized to produce P-efficient lentil cultivars. The lentil germplasm with potentially favorable root traits can be suggested to evaluated for other abiotic stress to use them in crop improvement programme. The scientific breakthroughs in root trait phenotyping have improved the chances of establishing trait-allele relationships. As a result, genotype-to-phenotype connections can be predicted and verified with exceptional accuracy, making it easier to find and incorporate favourable nutrition-related genes/QTLs in to breeding programme.

Chemical modification of capuramycins to enhance antibacterial activity.

OBJECTIVES: To extend capuramycin spectrum of activity beyond mycobacteria and improve intracellular drug activity. METHODS: Three capuramycin analogues (SQ997, SQ922 and SQ641) were conjugated with different natural and unnatural amino acids or decanoic acid (DEC) through an ester bond at one or more available hydroxyl groups. In vitro activity of the modified compounds was determined against Mycobacterium spp. and representative Gram-positive and Gram-negative bacteria. Intracellular activity was evaluated in J774A.1 mouse macrophages infected with Mycobacterium tuberculosis (H37Rv). RESULTS: Acylation of SQ997 and SQ641 with amino undecanoic acid (AUA) improved in vitro activity against most of the bacteria tested. Conjugation of SQ922 with DEC, but not AUA, improved its activity against Gram-positive bacteria. In the presence of efflux pump inhibitor phenylalanine arginine ß-naphthyl amide, MICs of SQ997-AUA, SQ641-AUA and SQ922-DEC compounds improved even further against drug-susceptible and drug-resistant Staphylococcus aureus. In Gram-negative bacteria, EDTA-mediated permeabilization caused 4- to 16-fold enhancement of the activity of AUA-conjugated SQ997, SQ922 and SQ641. Conjugation of all three capuramycin analogues with AUA improved intracellular killing of H37Rv in murine macrophages. CONCLUSIONS: Conjugation of capuramycin analogues with AUA or DEC enhanced in vitro activity, extended the spectrum of activity in Gram-positive bacteria and increased intracellular activity against H37Rv.

Identification of SQ609 as a lead compound from a library of dipiperidines.

We recently reported that compounds created around a dipiperidine scaffold demonstrated activity against Mycobacterium tuberculosis (Mtb) (Bogatcheva, E.; Hanrahan, C.; Chen, P.; Gearhart, J.; Sacksteder, K.; Einck, L.; Nacy, C.; Protopopova, M. Bioorg. Med. Chem. Lett.2010, 20, 201). To optimize the dipiperidine compound series and to select a lead compound to advance into preclinical studies, we evaluated the structure-activity relationship (SAR) of our proprietary libraries. The (piperidin-4-ylmethyl)piperidine scaffold was an essential structural element required for antibacterial activity. Based on SAR, we synthesized a focused library of 313 new dipiperidines to delineate additional structural features responsible for antitubercular activity. Thirty new active compounds with MIC 10-20 µg/ml on Mtb were identified, but none was better than the original hits of this series, SQ609, SQ614, and SQ615. In Mtb-infected macrophages in vitro, SQ609 and SQ614 inhibited more than 90% of intracellular bacterial growth at 4 µg/ml; SQ615 was toxic to these cells. In mice infected with Mtb, weight loss was completely prevented by SQ609, but not SQ614, and SQ609 had a prolonged therapeutic effect, extended by 10-15 days, after cessation of therapy. Based on in vitro and in vivo antitubercular activity, SQ609 was identified as the best-in-class dipiperidine compound in the series.

Comparison of different selection traits for identification of phosphorus use efficient lines in mungbean.

Phosphorus (P) is one of the major constraints for crop growth and development, owing to low availability and least mobility in many tropical soil conditions. Categorization of existing germplasm under P deficient conditions is a prerequisite for the selection and development of P efficient genotypes in the mungbean. In the present investigation, 36 diverse genotypes were categorized for phosphorus use efficiency traits using four different techniques for identification of phosphorus use efficient mungbean genotypes. The studied genotypes were categorized for P efficiency based on efficiency, responsiveness, and stress tolerance score of genotypes under normal and low P conditions. The mean values of traits, root dry mass, root to shoot ratio, and P utilization efficiency are significantly higher under low P conditions indicating the high responsiveness of traits to P deficiency. The presence of significant interaction between genotypes and P treatment indicates the evaluated genotypes were significantly affected by P treatment for studied traits. The total P uptake showed significant and positive correlations with root dry mass, shoot dry mass, total dry mass,and P concentration under both P regimes. Out of the four techniques used for the categorization of genotypes for P efficiency, three techniques revealed that the genotype PUSA 1333, followed by Pusa Vishal, PUSA 1031, and Pusa Ratna is efficient. The categorization based on stress tolerance score is the finest way to study variation and for the selection of contrasting genotypes for P efficiency. The identified P efficient genotypes would be valuable resources for genetic enhancement of P use efficiency in mungbean breeding.

Assessment of root phenotypes in mungbean mini-core collection (MMC) from the World Vegetable Center (AVRDC) Taiwan.

Mungbean (Vigna radiata L.) is an important food grain legume, but its production capacity is threatened by global warming, which can intensify plant stress and limit future production. Identifying new variation of key root traits in mungbean will provide the basis for breeding lines with effective root characteristics for improved water uptake to mitigate heat and drought stress. The AVRDC mungbean mini core collection consisting of 296 genotypes was screened under modified semi-hydroponic screening conditions to determine the variation for fourteen root-related traits. The AVRDC mungbean mini core collection displayed wide variations for the primary root length, total surface area, and total root length, and based on agglomerative hierarchical clustering eight homogeneous groups displaying different root traits could be identified. Germplasm with potentially favorable root traits has been identified for further studies to identify the donor genotypes for breeding cultivars with enhanced adaptation to water-deficit stress and other stress conditions.

Antimicrobial Effect of a Novel Chitosan Derivative and Its Synergistic Effect with Antibiotics.

Cationic polymers are promising antibacterial agents because bacteria have a low propensity to develop resistance against them, but they usually have low biocompatibility because of their hydrophobic moieties. Herein, we report a new biodegradable and biocompatible chitosan-derived cationic antibacterial polymer, 2,6-diamino chitosan (2,6-DAC). 2,6-DAC shows excellent broad-spectrum antimicrobial activity with minimum inhibitory concentrations (MICs) of 8-32 µg/mL against clinically relevant and multidrug-resistant (MDR) bacteria including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Furthermore, 2,6-DAC shows an excellent synergistic effect with various clinically relevant antibiotics proved by decreasing the MICs of the antibiotics against MDR A. baumannii and methicillin-resistant Staphylococcus aureus to <1 µg/mL. In vivo biocompatibility of 2,6-DAC is proved by a dosage of 100 mg/kg compound via oral administration and 25 mg/kg compound via intraperitoneal injection to mice; 2,6-DAC does not cause any weight loss and any significant change in liver and kidney biomarkers or the important blood electrolytes. The combinations of 2,6-DAC together with novobiocin and rifampicin show >2.4 log10 reduction of A. baumannii in murine intraperitoneal and lung infection models. The novel chitosan derivative, 2,6-DAC, can be utilized as a biocompatible broad-spectrum cationic antimicrobial agent alone or in synergistic combination with various antibiotics.

In vitro interactions between new antitubercular drug candidates SQ109 and TMC207.

The in vitro interactions of two new antitubercular drugs, SQ109 and TMC207, with each other and with rifampin (RIF) were evaluated. The combination of SQ109 with TMC207 (i) improved an already excellent TMC207 MIC for M. tuberculosis H37Rv by 4- to 8-fold, (ii) improved the rate of killing of bacteria over the rate of killing by each single drug, and (iii) enhanced the drug postantibiotic effect by 4 h. In no instance did we observe antagonistic activities with the combination of SQ109 and TMC207. Rifampin activates cytochrome P450 genes to reduce the area under the curve (AUC) for TMC207 in humans. The presence of RIF in three-drug combinations did not affect the synergistic activities of SQ109 and TMC207, and SQ109 also dramatically decreased the MIC of RIF. SQ109 was active by itself, and both its activity was improved by and it improved the in vitro activities of both RIF and TMC207.

In vitro antimicrobial activities of capuramycin analogues against non-tuberculous mycobacteria.

OBJECTIVES: To determine antibacterial activity of capuramycin analogues SQ997, SQ922, SQ641 and RKS2244 against several non-tuberculous mycobacteria (NTM). METHODS: In vitro antibiotic activities, i.e. MIC, MBC, rate of killing and synergistic interaction with other antibiotics, were evaluated. RESULTS: SQ641 was the most active compound against all the NTM species studied. The MIC of SQ641 was ≤0.06-4 mg/L for Mycobacterium avium complex (MAC; n = 20), 0.125-2 mg/L for M. avium paratuberculosis (MAP; n = 9), 0.125-2 mg/L for Mycobacterium kansasii (MKN;n = 2), 0.25-1 mg/L for Mycobacterium abscessus (MAB; n = 11), 4 mg/L for Mycobacterium smegmatis (MSMG; n = 1), and 1 and 8 mg/L for Mycobacterium ulcerans (MUL; n = 1), by microdilution and agar dilution methods, respectively. SQ641 was bactericidal against NTM, with an MBC/MIC ratio of 1 to 32, and killed all mycobacteria faster than positive control drugs for each strain. In chequerboard titrations, SQ641 was synergistic with ethambutol against both MAC and MSMG, and was synergistic with streptomycin and rifabutin against MAB. CONCLUSIONS: In vitro, SQ641 was the most potent of the capuramycin analogues against all NTM tested, both laboratory and clinical strains.

Genetic variation for root architectural traits in response to phosphorus deficiency in mungbean at the seedling stage.

Roots enable the plant to survive in the natural environment by providing anchorage and acquisition of water and nutrients. In this study, root architectural traits of 153 mungbean genotypes were compared under optimum and low phosphorus (P) conditions. Significant variations and medium to high heritability were observed for the root traits. Total root length was positively and significantly correlated with total root surface area, total root volume, total root tips and root forks under both optimum P (r = 0.95, r = 0.85, r = 0.68 and r = 0.82 respectively) and low P (r = 0.95, r = 0.82, r = 0.71 and r = 0.81 respectively). The magnitudes of the coefficient of variations were relatively higher for root forks, total root tips and total root volume. Total root length, total root surface area and total root volume were major contributors of variation and can be utilized for screening of P efficiency at the seedling stage. Released Indian mungbean varieties were found to be superior for root traits than other genotypic groups. Based on comprehensive P efficiency measurement, IPM-288, TM 96-25, TM 96-2, M 1477, PUSA 1342 were found to be the best highly efficient genotypes, whereas M 1131, PS-16, Pusa Vishal, M 831, IC 325828 were highly inefficient. Highly efficient genotypes identified would be valuable genetic resources for P efficiency for utilizing in the mungbean breeding programme.

Genome-Wide Association Analysis for Phosphorus Use Efficiency Traits in Mungbean (Vigna radiata L. Wilczek) Using Genotyping by Sequencing Approach.

Mungbean (Vigna radiata L. Wilczek) is an annual grain legume crop affected by low availability of phosphorus. Phosphorus deficiency mainly affects the growth and development of plants along with changes in root morphology and increase in root-to-shoot ratio. Deciphering the genetic basis of phosphorus use efficiency (PUE) traits can benefit our understanding of mungbean tolerance to low-phosphorus condition. To address this issue, 144 diverse mungbean genotypes were evaluated for 12 PUE traits under hydroponics with optimum- and low-phosphorus levels. The broad sense heritability of traits ranged from 0.63 to 0.92 and 0.58 to 0.92 under optimum- and low-phosphorus conditions, respectively. This study, reports for the first time such a large number of genome wide Single nucleotide polymorphisms (SNPs) (76,160) in mungbean. Further, genome wide association study was conducted using 55,634 SNPs obtained by genotyping-by-sequencing method. The results indicated that total 136 SNPs shared by both GLM and MLM models were associated with tested PUE traits under different phosphorus regimes. We have identified SNPs with highest p value (-log10(p)) for some traits like, TLA and RDW with p value (-log10(p)) of more than 6.0 at LP/OP and OP condition. We have identified nine SNPs (three for TLA and six for RDW trait) which was found to be present in chromosomes 8, 4, and 7. One SNP present in Vradi07g06230 gene contains zinc finger CCCH domain. In total, 71 protein coding genes were identified, of which 13 genes were found to be putative candidate genes controlling PUE by regulating nutrient uptake and root architectural development pathways in mungbean. Moreover, we identified three potential candidate genes VRADI11G08340, VRADI01G05520, and VRADI04G10750 with missense SNPs in coding sequence region, which results in significant variation in protein structure at tertiary level. The identified SNPs and candidate genes provide the essential information for genetic studies and marker-assisted breeding program for improving low-phosphorus tolerance in mungbean.

Activity of SQ641, a capuramycin analog, in a murine model of tuberculosis.

New delivery vehicles and routes of delivery were developed for the capuramycin analogue SQ641. While this compound has remarkable in vitro potency against Mycobacterium tuberculosis, it has low solubility in water and poor intracellular activity. We demonstrate here that SQ641 dissolved in the water-soluble vitamin E analogue alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) or incorporated into TPGS-micelles has significant activity in a mouse model of tuberculosis.