All the images were acquired at fixed camera and microscope settings for DNA and LNA with Nikon A1 confocal microscope. Fluorescence intensities were quantified by NIS elements (V 3.21.02) image analysis software (Nikon). The Signal to Noise (S/N) value is an indicator of sensitivity of the probe since it is a measure of both the signal and

the background. For this purpose no background correction was done, so that along with the actual signals of Portiera, the background noise of DNA and LNA could also be calculated for the same samples for 100 μm2 area respectively. S/N ratio value was obtained by dividing signal intensity with the background noise. Figure 3, where S/N ratio is plotted against increasing CX-5461 ic50 formamide concentration compares the two probes. AZ 628 purchase The LNA probe had nearly twice as much S/N values as DNA probe, while detecting Portiera. The highest S/N value (823) was obtained with LNA probe at 60% formamide concentration. Use of high formamide concentration for LNA probes in order to selleck reduce

the background noise, has been previously performed when detecting lactic acid bacteria [26]. In DNA probe the highest S/N value (334) was at 40% formamide concentration. It was evident from the graph that the LNA probe has higher signal and lower noise ratio than DNA at all formamide concentrations. At 0% formamide concentration even though the main signal Calpain is high, an equally high background noise

reduces the S/N ratio value in both DNA and LNA probes. In agreement to previous studies [12], we find that high sensitivity and stringency can be obtained by using LNA probes at high formamide concentrations while performing FISH in insect whole mounts. Figure 3 Signal to noise ratio of LNA and DNA probes while detecting the more abundant endosymbiont ( Portiera ). This graph depicts the signal to noise ratio, per 100 μm square area and plotted against increasing formamide concentration. No background correction was performed here. The value was calculated by dividing signal with the background of the same image and thus it gives a good idea about the binding efficiency of the probe. Here, LNA probe has a high signal to noise ratio at 60% formamide concentration followed by 30% formamide concentration, when compared to DNA probe. The signal of LNA probe is always high than the DNA probe at all formamide concentrations. Portiera was detected at 9 different formamide concentrations (0%-80%), both by DNA as well as the LNA probes. Fluorescence intensities were quantified by NIS elements (V 3.21.02) image analysis software (Nikon). Comparing LNA and DNA probes to detect Arsenophonus the secondary bacterial endosymbiont of Bemisia tabaci FISH detection of Arsneophonus 16 S rRNA was performed keeping all the conditions, but the laser settings, similar for DNA and LNA probes (Figure 4).

showed a lower agreement of 94% for erythromycin as well, but observed no very major errors for trimethoprim-sulfamethoxazole. Some other studies on direct methods for AST showed some very major errors for trimethoprim-sulfamethoxazole [15, 16, 18], but only Kerremans et al. [13] found a very high percentages of very major errors for this antibiotic in GPC, but not in GNR. Therefore, we conclude

that the direct Phoenix learn more method using SSTs can be used to reliably report results of AST for GPC, except for trimethoprim-sulfamethoxazole and erythromycin. The direct method of AST for GNR showed very good agreement with conventional methods for both Enterobacteriaceae and Pseudomonas species, comparable to the routinely used method, with essential agreements and categorical agreements of over 95% for all antibiotics AR-13324 mw tested (see table 3). Both very major errors occurred with trimethoprim-sulfamethoxazole see more in Pseudomonas aeruginosa strains that were correctly identified. For these strains, it would never be considered an adequate treatment, due to intrinsic resistance. These errors thus would not have clinical

consequences. Funke et al. [18] also described a categorical agreement of 99.0%, which is comparable with or higher than results from studies on other direct methods of AST [7, 13–16, 26]. Therefore, we conclude that also for GNR, results of the direct Phoenix method for AST can be used to guide antibiotic therapy in bloodstream infections. The strains tested in this study are a representative

sample of the strains most frequently encountered in clinical practice. A limitation of the study is the low number of tested Enterococcus and Pseudomonas strains (3 and 7, respectively), however, both groups show very good agreement, with only few errors. Inoculating ID and AST broth by using SSTs can be performed as soon as blood culture bottles are taken out of the BACTEC system and takes approximately 30 minutes, whereas a subculture Bacterial neuraminidase takes up to 24 hours. Therefore, by using the direct method, results of ID and AST can be available up to 23.5 hours earlier than with the routinely used method. Conclusions From these results we conclude that AST by inoculating Phoenix panels with bacteria harvested directly from positive blood culture bottles is as reliable as using bacteria from a subculture on agar, with the exception of results for erythromycin and trimethoprim-sulfamethoxazole in Staphylococcus and Enterococcus spp., which should not be reported due to their low agreement. Results of ID of Enterobacteriaceae were shown to be very reliable. ID of Staphylococcus and Enterococcus spp. was not performed with the direct method. Caution is warranted about interpretation of results of Enterococcus and Pseudomonas spp., of which only a limited number of strains was tested.

albicans biofilms. Once it reaches

the cell, KSL-W can potentially act on the cytoplasmic membrane as well as on intracellular targets [49–51]. The action MEK inhibitor review of KSL-W against C. albicans may operate through the modulated expression of certain C. albicans genes that control growth [52], transition [53], and biofilm formation [54]. We therefore examined the effect of KSL-W on a number of genes either directly or indirectly involved in phase transition and biofilm formation. EFG1 and NRG1 expression was assessed under hyphae/non-hyphae-inducing conditions. Our results show that KSL-W increased NRG1 mRNA expression twofold under non-hyphae-inducing conditions; however, under hyphae-inducing conditions, KSL-W significantly reduced NRG1 gene expression. These findings contrast with other reports that an increased NRG1 selleckchem expression contributes to repressing various hypha-specific

genes [55, 56]. This confirms that the effect of KSL-W in controlling C. albicans Selleckchem Vorinostat virulence does not take place through NRG1. KSL-W was also able to decrease EFG1 mRNA expression, when C. albicans was maintained under hyphae-inducing conditions. EFG1p has been found to be a central regulator of C. albicans, as it is required for the development of a true hyphal growth form, and EFG1 is considered to be essential in the interactions between C. albicans and human host cells [7, 8]. The downregulation of this gene by KSL-W points to the singular role of this

antifungal peptide. Thus the effect of KSL-W on C. albicans transition can be manifested through a repression of certain genes, such as EFG1 and NRG1. KSL-W has a significant inhibitory effect on EAP1 mRNA expression. As a member of the heptaminol GPI-CWP family [5, 57], deleting EAP1 can reduce the adhesion of C. albicans to different surfaces. This suggests that treatment with KSL-W may reduce EAP1 expression, which in turn may contribute to reducing C. albicans adhesion and ultimately, biofilm formation and pathogenesis. KSL-W was also shown to reduce HWP1 mRNA expression, particularly when C. albicans was cultured under hyphae-inducing conditions. HWP1 is a downstream component of the cAMP-dependent PKA pathway and is positively regulated by EFG1 [58]. The transcript level of HWP1 decreased with the KSL-W treatment at low and high concentrations. These data suggest that KSL-W indeed impacts the activity of the cAMP–EFG1 pathway and leads to an alteration of C. albicans growth and morphogenesis. Further studies are therefore required to investigate the invasion/virulence of KSL-W-treated C. albicans. It is well known that Candida pathogenesis can be established by virtue of Candida growth and yeast-to-hyphae morphogenesis. Specific SAP genes were found to be preferentially expressed by Candida hyphal forms [10, 15, 59]. Because KSL-W downregulated C. albicans growth and transition, this may have occurred through a modulation of the SAP genes.

0 0.51 ± 0.1   Treatment 0.46 ± 0.7 0.42 ± 0.6 Triacylglycerols (mmol/L)a Control 1.01 ± 0.1 1.10 ± 0.3   Treatment 1.02 ± 0.2 0.91 ± 0.1 b, c FATTY ACID PROFILE Pre-treatment buy STA-9090 Post-treatment ALA (umol/L) Control 22.61 ± 3.4 20.22 ± 2.1   Treatment 23.18 ± 2.3 19.74 ± 1.7 AA (umol/L) Control 670.74 ± 60.1 696.77 ± 87.1   Treatment 599.91 ± 33.9 613.12 ± 27.0 DHA (umol/L)a Control 83.23 ± 10.3

103.23 ± 15.0   Treatment 91.18 ± 9.7 125.58 ± 11.9 b, c EPA (umol/L) Control 22.49 ± 3.4 20.59 ± 6.8   Treatment 17.93 ± 3.1 20.77 ± 2.9 a Significant overall group × time ANCOVA statistical effect (P < 0.01) b Represents a significant within group statistical effect (P < 0.05) c Represents a significant change score different than control (P < 0.05) Total-C (Total cholesterol), LDL-C (low density cholesterol, HDL-C (high density cholesterol), VLDL (very low AZD1480 research buy density cholesterol) ALA (alpha-linolenic acid), AA (arachadonic acid), DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid) Discussion The primary findings of our current pilot study show that MicroN3 fortified foods can

increase plasma N3 concentrations, while positively modulating triacylglycerols within 2 weeks in a population who would be considered to have normal triacylglycerols concentrations. This latter effect on triacylglycerols is of particular interest as studies showing a reduction in triacylglycerols typically range between 2–4 g of N3 ingestion per day [9]. More recent studies, however, have shown attenuated postprandial triacylglycerols with as little as 1 g/d with chronic administration [10]. The results of our study are appealing as the cohort we examined represents a population similar to the United States national average and the foods ingested were well Vasopressin Receptor tolerated. Collectively, higher N3 consumption has the potential to positively affect many heath issues such as pregnancy, cognitive development and learning in infants and children,

visual development, immune and inflammatory responses, rheumatoid arthritis, ulcerative colitis, Crohn disease, eczema, asthma, and type 1 diabetes, metabolic syndrome, type 2 diabetes, obesity, cardiovascular https://www.selleckchem.com/products/ly2606368.html disease and lipid metabolism, neurologic degeneration and mental health and mood disorders [11, 12]. Moreover, the U.S. Food and Drug Administration has given a qualified health claim status to EPA and DHA N3 fatty acids, stating that supportive but not conclusive research shows that consumption of EPA and DHA may reduce the risk of coronary heart disease [13]. A fundamental difficulty surrounding the recommendation and ingestion of N3 fatty acids containing high quantities of EPA and DHA is the observation that the highest concentrations of these fatty acids are found in cold water fish [14]. Unfortunately, many individuals are resistant to consuming fish for a variety of reasons including taste, gastrointestinal distress and fish odor [2].

A positive fold change indicates the gene was expressed to a greater extent within a condition. An asterisk (*) indicates that the gene

was significantly differentially expressed (p <0.05, t-test) and the error bars on the RT-qPCR data represent the standard deviation between the biological replicates GDC-0449 manufacturer of mycelia, spherules at day 2 and spherules at day 8. A recent paper by Whiston et al. assessed transcription in C. immitis and C. posadasii mycelia and day 4 spherules by RNA-seq [13]. We have compared our results to theirs. The two studies used different methods for assessing changes in gene expression. We used microarray technology to estimate transcript abundance VX-689 nmr while Whiston et al. used RNA-seq to estimate transcript abundance [13]. The literature suggests that these methods should yield comparable results [24]. Despite this difference in methodology, we confirmed the upregulation of 25% of the genes that Whiston found to be upregulated in spherules. Conversely, 43% of genes that we have found to be upregulated in day 2 and day 8 spherules were also upregulated in day 4 spherules in the Whiston study (Additional file 5: Figure S2). Despite the differences in the two studies many of our conclusions are similar (see

below). We know from previous experiments that some genes are overexpressed in spherules compared to mycelia. Some of these genes, such as the spherule outer wall glycoprotein (CIMG_04613) [25] and the parasitic-phase specific protein PSP-1 (CIMG_05758) [26] were up regulated more than four fold in spherules in this experiment (Additional file 4: Table S2). nearly Other

genes, such as the metalloproteinase Mep1 (CIMG_06703), which has been found to be expressed at high levels in endosporulating spherules in C. posadasii was not found to be over-expressed in this experiment [27]. We also examined the expression level of the Mep1 gene by RT-qPCR and found that its expression was slightly downregulated in spherules compared to mycelia, rather than upregulated as previously reported (see below). Whiston et al. also examined the expression of this gene and found that it was upregulated in C. posadasii spherules but not C. immitis spherules [13]. Confirmation of differential expression by RT-qPCR Twenty-four differentially expressed genes as detected by microarray analysis were learn more selected for confirmation by RT-qPCR (Figure  3). Genes were selected for RT-qPCR confirmation of gene expression based on the magnitude of fold change (up- or downregulation) between mycelia and day 2 spherules, mycelia and day 8 spherules, and day 2 and day 8 spherules, and their identification in the PFAM or GO analysis. The significant differential expression (p < 0.05, t-test) of each of these 24 genes was confirmed for at least one of the three comparison groups.

Appl Phys Lett 2008, 92:GDC 0032 143101. 143CrossRef 5. Zhang LH, Yang HQ, Li L:

Synthesis and characterization of core/shell-type ZnO nanorod/ZnSe nanopartical composites by a one-step hydrothermal route. Mater Chem Phys 2010, 120:526–531.CrossRef 6. Caruso F: Nanoengineering of particle surfaces. Adv Mater 2001, 13:11–22.CrossRef 7. Xiong SL, Shen JM, Xie Q, Gao YQ, Tang Q, Qian YT: A precursor-based route to ZnSe nanowire bundles. Adv Funct Mater 2005, 15:1787–1792.CrossRef 8. Wang CR, Wang J, Li Q, Yi GC: ZnSe-Si bi-coaxial nanowire Selleck Pevonedistat heterostructures. Adv Funct Mater 2005, 15:1471–1477.CrossRef 9. Wu ZM, Zhang Y, Zheng JJ, Lin XG, Chen XH, Huang BW, Wang HQ, Huang K, Li SP, Kang JY: An all-inorganic type-II heterojunction array with nearly full solar spectral response Smad3 signaling based on ZnO/ZnSe core/shell nanowires. J Mater Chem 2011, 21:6020–6026.CrossRef 10. Zhang Y, Wu ZM, Zheng JJ, Lin XG, Zhan HH, Li SP, Kang JY, Bleusec J, Mariette H: ZnO/ZnSe type II core-shell nanowire array solar cell. Sol Energ Mat Sol C 2012, 102:15–18.CrossRef 11. Wang K, Chen JJ, Zhou WL, Zhang Y, Yan YF, Pern J, Mascarenhas A: Direct growth of highly mismatched type II ZnO/ZnSe core/shell nanowire arrays on transparent conducting oxide substrates for solar cell applications. Adv Mater 2008, 20:3248–3253.CrossRef 12. Zhang

Y, Sturge MD, Kash K: Temperature dependence of luminescence efficiency, exciton transfer, and exciton localization in GaAs/Al x Ga 1-x As quantum wires and quantum dots. Phys Rev B 1995, 51:13303–13314.CrossRef 13. Xu N, Cui Y, Hu ZG, Yu WL, Sun J, Xu N, Wu JD: Photoluminescence and low-threshold lasing of ZnO nanorod arrays. Opt Express 2012, 20:14857–14863.CrossRef 14. Cullity BD, Stock SR: Elements of X-ray Diffraction. 3rd edition. Upper Saddle River, NJ: Prentice Hall, Inc; 2001:170. 15. Mitra SS, Brafman O, Daniels WB, Crawford RK: Photoluminescence and low-threshold lasing of ZnO

nanorod arrays. Phys Rev 1969, 186:942–944.CrossRef 16. Irwin JC, Lacombe J: Second-order Raman spectrum Staurosporine ic50 of ZnSe. Can J Phys 1970, 48:2499–2506.CrossRef 17. Hu ZD, Duan XF, Gao M, Chen Q, Peng LM: ZnSe nanobelts and nanowires synthesized by a closed space vapor transport technique. J Phys Chem C 2007, 111:2987–2991.CrossRef 18. Anand S, Verma P, Jain KP, Abbi SC: Temperature dependence of optical phonon lifetime in ZnSe. Physica B 1996, 226:331–337.CrossRef 19. Damen TC, Porto SPS, Tell B: Raman effect in zinc oxide. Phys Rev 1966, 142:570–574.CrossRef 20. Arguello CA, Rousseau DL, Porto SPS: First-order Raman effect in wurtzite-type crystals. Phys Rev 1969, 181:1351–1363.CrossRef 21. Scoot JF: UV resonant Raman scattering in ZnO. Phys Rev B 1970, 2:1209–1211.CrossRef 22. Bundesmann C, Ashkenov N, Schubert M, Spemann D, Butz T, Kaidashev EM, Lorenz M, Grundmann M: Raman scattering in ZnO thin films doped with Fe, Sb, Al, Ga, and Li.

Nonetheless in the same studies, high IgG seroprevalence has been observed in the control

sera ranging from 36% (Virotech assay) to 93% (Ani Labsystems assay). The variability of the ELISA results observed in these studies suggests the need for improved sensitivity and specificity among commercialised serological assays used to detect M. pneumoniae infection [8]. Recently, many studies have reported great interest in using a recombinant protein corresponding to the C-terminal portion of the P1 adhesin, which has been described as the immunodominant antigen in M. pneumoniae [2, 13–17]. Antigenic properties of recombinant proteins P116 and P30 have also been shown [15, 18, 19]. A combination of frequently recognized antigens could be useful for diagnostic purposes. Thus, the identification of antigenic M. pneumoniae RTI-related #selleck products randurls[1|1|,|CHEM1|]# proteins appears to be a prerequisite for the development of serological test kits based on recombinant antigens. In this study, we used serologic proteome analysis of M. pneumoniae

M129 total extracts to simultaneously identify candidate antigens SB525334 inducing an antibody response [20]. We focused on the ATP synthase beta subunit (AtpD) of M. pneumoniae as it was likely to generate an antibody response in M. pneumoniae-infected children and adults at an early stage of infection. The atpD gene (mpn598) contains an open reading frame of 1,428 nucleotides and encodes a protein of 475 amino acids, with a calculated molecular weight of 52,486 Da

[21–23]. It was cloned and expressed in E. coli to obtain recombinant protein. We then compared the serological performance of this antigen with a previously described recombinant C-terminal fragment of the P1 adhesin (rP1-C) [2, 13, 15], using in-house IgM, IgA and IgG ELISAs and the commercial Ani Labsystems ELISA that uses an adhesin P1-enriched whole extract. We further evaluated the performance of the combination rAtpD and rP1-C IgM by binary logistic regression analysis to compare results between the recombinant Vildagliptin antigens, either alone or together, and the enriched whole extract. Results Identification of the AtpD antigen by serologic proteome analysis The total protein fraction obtained from the M. pneumoniae M129 strain was separated by two dimensional gel electrophoresis (2D-E) (Fig. 1A) and the staining pattern of the 2D immunoblots was probed with 10 different serums samples from patients with RTIs (Fig. 1B) or healthy blood donors (Fig. 1C). The protein identities of six spots that were detected by at least one of the serum samples from the 10 RTI patients were determined using MALDI-TOF mass spectrometry following in-gel tryptic digestion (Table 1). Of the six proteins identified, four (P1 protein, enolase, the ATP synthase beta subunit and the pyruvate dehydrogenase beta subunit) were highly detected by serum samples from patients (Fig.

Helicobacter 2003, 8:95–104.CrossRefPubMed 5. Cameron IC, Azmy IA: Thromboprophylaxis in patients undergoing surgery for breast cancer. Breast 2001, 10:535–537.CrossRefPubMed 6. White SW, Zheng J, Zhang YM, Rock : The structural biology

of type II fatty acid biosynthesis. Annu Rev Biochem 2005, 74:791–831.CrossRefPubMed 7. Liu W, Luo C, Han C, Peng S, Yang Y, Yue J, Shen X, Jiang H: A new beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Helicobacter pylori : Molecular cloning, enzymatic characterization, and structural modeling. Biochem Biophys Res Commun 2005, 333:1078–1086.CrossRefPubMed 8. Zhang L, Liu W, Hu T, Du L, Luo C, Chen K, Shen X,

Jiang H: Structural basis buy AZD5363 for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ). J Biol Chem 2008, 283:5370–5379.CrossRefPubMed 9. Alves DS, Perez-Fons L, Estepa A, Micol V: Membrane-related effects underlying the biological activity of the anthraquinones emodin and barbaloin. Biochem Pharmacol 2004, 68:549–561.CrossRefPubMed 10. Wang HH, Chung JG: Emodin-induced inhibition of growth and DNA damage in the Helicobacter pylori. Curr Microbiol 1997, 35:262–266.CrossRefPubMed 11. Chang CH, Lin CC, Yang JJ, Namba T, Hattori M: Anti-inflammatory Bafilomycin A1 price effects of emodin from ventilago leiocarpa. Am J Chin Sitaxentan Med 1996, 24:139–142.CrossRefPubMed 12. Cai J, Razzak A, Hering J, Saed A, Babcock TA, Helton S, Espat NJ: selleck chemicals Feasibility evaluation of emodin (rhubarb extract) as an inhibitor of pancreatic cancer cell proliferation in vitro. JPEN J Parenter Enteral Nutr 2008, 32:190–196.CrossRefPubMed 13. Sato M, Maulik G, Bagchi D, Das DK: Myocardial protection by protykin, a novel extract of trans-resveratrol and emodin. Free Radic Res 2000, 32:135–144.CrossRefPubMed 14. Kuo YC, Meng HC, Tsai WJ: Regulation of cell proliferation, inflammatory cytokine production and calcium mobilization

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The expression of cchA was strongly down-regulated by the absence of AdpA at times D and T (Figure 1b): note that despite repeated efforts, cchA expression could not be detected in samples corresponding to times A

to C for unknown reasons. The findings selleck kinase inhibitor for gene expression as determined by microarrays and by qRT-PCR were consistent, with the exception of those for ramR. The expression of ramR observed by qRT-PCR at time T differed from that determined in microarray experiments (Table 1), suggesting that some of our microarray data are Y27632 flattened. Nevertheless, these qRT-PCR experiments confirmed that the expression of the six selected genes is indeed AdpA-dependent in S. lividans at every growth time studied. Direct binding of AdpA to the promoter regions of S. lividans AdpA regulon members DUB inhibitor To determine whether S. lividans AdpA directly controls these genes, we searched for potential AdpA-binding sites in their promoter regions in silico. A consensus AdpA-binding sequence (5′TGGCSNGWWY3′) has been established in S. griseus, and AdpA can bind up to five sites between positions -260 bp and +60 bp with respect to the transcriptional start point of the target gene [10]. BLAST analysis revealed

that the S. griseus AdpA DNA-binding domain is conserved in S. coelicolor and S. lividans AdpAs (data not shown) suggesting that all three species share the same AdpA-binding consensus sequence. The DNA sequences upstream from the S. coelicolor ramR and hyaS genes and the intergenic

stiripentol region between the divergently transcribed genes cchA/cchB, SCO0774/SCO0775 and SCO6197/SCO6198 were analyzed using PREDetector software [39] and a matrix was generated with identified S. griseus AdpA-binding sequences [10, 23, 25]. Between three and nine putative AdpA-binding sites were detected within the promoter region of the S. coelicolor genes and by analogy in orthologous S. lividans AdpA-dependent genes (Table 2, location with respect to translation start point). During the course of this study, the S. lividans 1326 genome sequence became available [24] (but not in a form suitable for analysis with PREDetector (version 1.2.3.0) [39]) and its analysis suggested that the position and composition of AdpA-binding sites were different from those predicted. The putative AdpA-binding sites of S. lividans cchA/cchB at -101 nt and -86 nt are GGGCCGGTTC and TGGCTGGAAC, respectively. The AdpA-binding sites located upstream of SLI0755, SLI6586, and hyaS differ from their S. coelicolor orthologs (see Table 2, changes in the location from translation start site are indicated in bracket). Table 2 AdpA-binding sites identified in silico in the promoter regions of S. lividans AdpA-dependent genes a S. coelicolor gene (S.

Conclusions In summary PA-824 exhibited greater bactericidal activity

on non-replicating organisms (persisters) under normal pH than that of RIF and PZA, which may help in shortening the duration of treatment. Interestingly, the dose of 12.5 μg/ml and 21 days treatment was Ro 61-8048 ic50 observed to have an ability to reduce the bacterial count to zero, which may offer key insights while setting the doses for in vivo/clinical studies. From the combinatorial analysis, ligand 8 (PA-824-Moxifloxacin ester conjugate) showed the most potent activity against both wild type and mutant Ddn receptors this website and hence needs further in vitro investigation of its enantiomeric binding properties with the Ddn receptor. Acknowledgement The authors thank the Director and the staff, National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai for their valuable support with the conduct of wet lab experiments and the TB Global Alliance for supplying Cilengitide chemical structure the PA-824 drug. References 1. Global Tuberculosis Report: Global Tuberculosis Report. 2012. http://​apps.​who.​int/​iris/​bitstream/​10665/​75938/​1/​9789241564502_​eng.​pdf 2. Barry CE III, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, Schnappinger D, Wilkinson RJ, Young D: The spectrum of latent tuberculosis: rethinking the biology and intervention

strategies. Nat Rev Microbiol 2009, 7:845–855.PubMed 3. Boshoff HIM, Barry CE III: Tuberculosis—metabolism and respiration in the absence of growth. Nat Rev Microbiol 2005, 3:70–80.PubMedCrossRef 4. Sharma SK, Mohan A: Multidrug-resistant tuberculosis: a menace that threatens to destabilize tuberculosis control. Chest 2006, 130:261–272.PubMedCrossRef 5. Kantardjieff K, Rupp B: Structural bioinformatic approaches to the discovery of new antimycobacterial drugs. Curr Pharm Des 2004, 10:3195–3211.PubMedCrossRef 6. TB alliance 2012.

7. Diacon AH, et al.: Early bactericidal Org 27569 activity and pharmacokinetics of pa-824 in smear-positive tuberculosis patients. Antimicrob Agents Chemother 2010,54(8):3402–3407.PubMedCrossRef 8. Tyagi S, Nuermberger E, Yoshimatsu T, Williams K, Rosenthal I, Lounis N, Bishai W, Grosset J: Bactericidal activity of the nitroimidazopyran pa-824 in a murine model of tuberculosis. Antimicrob Agents Chemother 2005,49(6):2289–2293.PubMedCrossRef 9. Manjunatha UH, Helena B, Cynthia S, Dowd , Liang Z, Thomas J, Albert , Jason E, Norton , Lacy D, Thomas D, Siew Siew P, Clifton E, Barry : Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis . PNAS 2006,103(2):431–436.PubMedCrossRef 10. Wayne LG, Hayes LG: An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 1996,64(6):2062–2069.PubMed 11. Wayne LG: Synchronized replication of Mycobacterium tuberculosis . Infect Immun 1977, 17:528–530.PubMed 12.