The shape of the bottle (size and thickness) was an additional factor identified by patients as a barrier to adherence. Based on the findings of this small scale study, an improvement in the assessment process of patients’ ability to administer their drops is essential. In rural settings, the pharmacists’ role in this process, through medicines use review and education is key since some patients may not have access to this advice in the clinic. The growing trend towards delivery of medication direct to patients’ homes raises further

questions on the role that Community Pharmacy can play in supporting patients to use their eye-drop medication. The findings further support SRT1720 the need for pharmacists to prompt patients for information about eye medication as part of their drug-history taking. 1. Schwartz, GF. Compliance and persistency in glaucoma follow up treatment. Current Opinion in Ophthalmology 2005; 16: 114–121. 2. Nordmann, J-P et al. Identification of non compliant glaucoma patients using Bayesian networks and Eye-Drop Satisfaction Questionnaire. Clinical Ophthalmology 2010; 1489–1496. Michael Wilcock, Penny Self, Stephen Dickinson, Paul Johnston, Jon Stratton, Rob Parry Royal Cornwall Hospitals NHS Trust, Truro, UK

Switching branded immunosuppressants (IS) in a controlled manner provides an opportunity to generate savings. Following advice to switch, GP prescriptions for the chosen branded versions of tacrolimus and mycophenolate mofetil increased four-fold and six-fold respectively. No significant adverse outcomes have been Cabozantinib nmr observed. There is a need Methocarbamol to continue to provide high quality care at lower cost. One established mechanism is to switch to generic medication. There is understandable hesitancy in switching when the medication is essential for organ function.1 The experience of one Renal Unit in switching stable renal transplant recipients (RTRs)

from their originator brand IS to an alternative less expensive brand is reported here. The district general hospital based Renal Unit takes over management of RTRs after the initial peri-transplant period (usually 3 months). Following this period the majority of IS is prescribed via primary care with secondary care supervision using shared care guidelines. The Unit currently manage approximately 200 RTRs. The Unit’s primary renal transplant centre switched to the Adoport® brand of tacrolimus approximately 18 months ago resulting in a population of RTRs on two brands of tacrolimus. For unity it was decided to switch all patients from Prograf® to Adoport®. At the same time it was recommended to switch from the originator mycophenylate mofetil (Cellcept®) to an alternative brand (Myfenax®). A cost analysis suggested potential savings of up to £200k per year if all patients switched to the less expensive brands, though this was viewed as an unrealistic expectation.

S3). Increased sensitivity to ETBR was also observed in complemented dcm strains (Table 3). Dinaciclib mouse These data indicate that there is an inverse relationship between the presence of the dcm gene and ETBR resistance. Based on the qPCR and drug susceptibility

data, our model is that increased sugE expression in the absence of Dcm is responsible for ETBR resistance. The results of Sulavik et al. and Nishino et al. indicate that there are several transporter genes that are linked to ETBR resistance via overexpression and knockout studies including acrAB, acrEF, emrE, mdfA, tolC, yhiUV, and ydhE (Nishino & Yamaguchi, 2001; Sulavik et al., 2001). The biggest effect was with acrAB, as the MIC increased > 32-fold when acrAB was overexpressed and decreased > 250-fold when acrAB was disrupted. Thus, we were interested to know if there are other transporters in addition to SugE that are up-regulated in the absence of cytosine DNA

methylation that could contribute to ETBR resistance. We are currently using DNA microarrays to generate gene expression profiles of wild-type cells, dcm knockout cells, and wild-type cells treated with 5-azacytidine learn more at both logarithmic phase and stationary phase. In initial experiments, we observed no transporters from the list above that were up-regulated both in the absence of dcm and presence of 5-azacytidine (> twofold) (K.T. Militello, R.D. Simon, A.H. Mandarano, S.M. Hennick & A.C. DiNatale, in preparation). Moreover, none of the transporters listed above were up-regulated > twofold in the absence of dcm alone. Thus, our model is that SugE is responsible for the ETBR resistance observed, but it is not possible at this point to rule out the effect of other transporters

on ETBR resistance or small contributions by multiple transporters that result in a detectible change in ETBR resistance. In total, our experiments have uncovered a new and unexpected phenotype for the loss of Dcm; changes in sensitivity to ETBR. Our data also brings up the possibility that potential changes in DNA methylation levels due to nutritional status, presence of restriction-modification systems, and/or epigenetic mechanisms may influence the sensitivity of prokaryotes to antibacterial unless compounds through changes in gene expression and thus link specific environments to differential antibiotic resistance. We thank the Geneseo Foundation for funding, Ashok Bhagwat (Wayne State University) for plasmid DNAs, and Devin Chandler-Militello, Sarah Ackerman, Leanne Chen, and Erika Valentine for manuscript editing. “
“The presence of toxigenic cyanobacteria capable of biosynthesis of cylindrospermopsin (CYN) was measured in 24 water samples collected from the lakes Bytyńskie (BY) and Bnińskie (BN) in the Western Poland. The study also covered analysis of toxigenicity and production of CYN by the culture of Cylindrospermopsis raciborskii isolated from BY.

S3). Increased sensitivity to ETBR was also observed in complemented dcm strains (Table 3). http://www.selleckchem.com/products/AG-014699.html These data indicate that there is an inverse relationship between the presence of the dcm gene and ETBR resistance. Based on the qPCR and drug susceptibility

data, our model is that increased sugE expression in the absence of Dcm is responsible for ETBR resistance. The results of Sulavik et al. and Nishino et al. indicate that there are several transporter genes that are linked to ETBR resistance via overexpression and knockout studies including acrAB, acrEF, emrE, mdfA, tolC, yhiUV, and ydhE (Nishino & Yamaguchi, 2001; Sulavik et al., 2001). The biggest effect was with acrAB, as the MIC increased > 32-fold when acrAB was overexpressed and decreased > 250-fold when acrAB was disrupted. Thus, we were interested to know if there are other transporters in addition to SugE that are up-regulated in the absence of cytosine DNA

methylation that could contribute to ETBR resistance. We are currently using DNA microarrays to generate gene expression profiles of wild-type cells, dcm knockout cells, and wild-type cells treated with 5-azacytidine Selumetinib order at both logarithmic phase and stationary phase. In initial experiments, we observed no transporters from the list above that were up-regulated both in the absence of dcm and presence of 5-azacytidine (> twofold) (K.T. Militello, R.D. Simon, A.H. Mandarano, S.M. Hennick & A.C. DiNatale, in preparation). Moreover, none of the transporters listed above were up-regulated > twofold in the absence of dcm alone. Thus, our model is that SugE is responsible for the ETBR resistance observed, but it is not possible at this point to rule out the effect of other transporters

on ETBR resistance or small contributions by multiple transporters that result in a detectible change in ETBR resistance. In total, our experiments have uncovered a new and unexpected phenotype for the loss of Dcm; changes in sensitivity to ETBR. Our data also brings up the possibility that potential changes in DNA methylation levels due to nutritional status, presence of restriction-modification systems, and/or epigenetic mechanisms may influence the sensitivity of prokaryotes to antibacterial Methamphetamine compounds through changes in gene expression and thus link specific environments to differential antibiotic resistance. We thank the Geneseo Foundation for funding, Ashok Bhagwat (Wayne State University) for plasmid DNAs, and Devin Chandler-Militello, Sarah Ackerman, Leanne Chen, and Erika Valentine for manuscript editing. “
“The presence of toxigenic cyanobacteria capable of biosynthesis of cylindrospermopsin (CYN) was measured in 24 water samples collected from the lakes Bytyńskie (BY) and Bnińskie (BN) in the Western Poland. The study also covered analysis of toxigenicity and production of CYN by the culture of Cylindrospermopsis raciborskii isolated from BY.

For example, of the 34 patients in the MONET trial with virological failure by the TLOVR algorithm, only eight (24%) had confirmed elevations of HIV RNA > 400 copies/mL, none developed phenotypic resistance to PIs and 24 (71%) had HIV RNA levels < 50 copies/mL at the end of the trial (week 144). Use of an ITT (switches not considered failures) endpoint can help to evaluate the long-term consequences of viral rebound [20]; these may differ between drug classes which have different potency or genetic barriers to the emergence of drug DAPT clinical trial resistance

[21, 22]. In addition to concerns over low-level virological rebound during PI monotherapy, there has been concern over the potential for HIV replication in the central nervous system (CNS). A recent review of the evidence has not shown an increased risk for CNS virological failure or neurocognitive impairment during treatment with PI monotherapy [23]. However, larger, long-term trials of PI monotherapy are in progress, with dedicated substudies to examine this issue in AZD8055 more detail [24]. In summary, in this randomized study of patients with HIV RNA < 50 copies/mL on stable antiretroviral treatment and with no history of virological

failure, DRV/r monotherapy showed noninferior efficacy to DRV/r + 2NRTIs in the ITT (switches not considered failures) analysis, but not in the primary TLOVR switch equals failure analysis. No phenotypic resistance

to PIs developed in either treatment arm. As shown in the MONET trial, the benefits of DRV/r monotherapy are a simplified treatment with a single boosted PI, which avoids the adverse events, costs and potential drug resistance associated with the use of other drug classes. There appears to be a slightly higher risk of elevations in HIV RNA for patients taking DRV/r monotherapy. However, these patients could be successfully resuppressed, with HIV RNA returning < 50 copies/mL, either by continuation of the DRV/r monotherapy or by intensification with NRTIs. 17-DMAG (Alvespimycin) HCl We thank the investigators, study coordinators, site and data managers and the patients for their contributions. J.R.A. is an investigator from the Programa de Intensificacio’n de la Actividad Investigadora en el SNS (I3SNS) 2008, INT07/147. “
“Men diagnosed with rectal gonorrhoea (GC) and chlamydia (CT) have engaged in unprotected receptive anal intercourse. We reviewed the HIV positivity and HIV viral loads (VLs) of men who had rectal GC and CT testing to evaluate potential HIV acquisition and transmission risk. Rectal GC and CT testing data for men attending the Maricopa County STD clinic during the period from 1 October 2011 to 30 September 2013 were cross-matched with HIV surveillance data to identify men with HIV coinfection. We examined HIV status, HIV diagnosis date, and the values of VL collected nearest to the date of reported rectal infection.

Overall, 14.8% of the samples with discordant or indeterminate results were identified as HIV-positive using direct

diagnosis. With the identification of four new cases using the nucleic acid detection test, the HIV prevalence in MSM increased by 0.3% (from 10.4 to 10.7%). The results of this study suggest the importance of including nucleic acid detection in the HIV algorithm for MSM with HIV-indeterminate WB results and those with HIV-negative WB results and discordant results in screening assays, in order to decrease HIV transmission among this population with a high HIV prevalence and incidence. In Argentina, HIV diagnosis in adults follows the Centers for Disease Control and Prevention (CDC) recommendations which suggest antibody testing using one or two enzyme immunoassay tests (EIAs) and one confirmatory test [Western Selleckchem Alpelisib blot (WB)] [1]. However, strategies limited to antibody testing may fail to detect infected individuals during early primary infection, with serious implications for public health. The early diagnosis of acute HIV infections may benefit patients by permitting clinical interventions, which CP868596 can limit viral spread by decreasing viral loads and thus reducing the risk of transmission [2-4]. The most sensitive techniques to identify acute infections are based on the detection of viral nucleic acid by nucleic acid amplification testing (NAAT). Strategies

focused on pooled HIV RNA detection can be feasible and cost-effective. However, when the expected number of acute infections is high (as a consequence of high prevalence and incidence rates), use of this algorithm hinders the reporting of results on time and increases the overall cost of testing. In these cases, it is advisable to carry out individual nucleic acid testing. The first HIV prevalence study on men who have sex with men (MSM) from Buenos Aires revealed a rate of 13.8% [5]. The results of this study also showed that a large number of MSM (≈ 50%) were engaged in unprotected sexual

intercourse. A recent study conducted in MSM showed the same trend (HIV prevalence 10.4%; HIV incidence 6.3% persons/year) [6]. In order to decrease HIV transmission among MSM, it is necessary to improve early HIV diagnosis. Ribonucleotide reductase Therefore, the general objective of this study was to contribute to reducing HIV transmission through the identification of HIV antibody-negative and NAAT-positive MSM during acute infection. A total of 1549 MSM were included in an HIV cross-sectional study conducted during 2006–2008 [6]. All the patients had to sign an informed consent form to participate in the study. HIV diagnosis was performed as described previously using two screening tests, an enzyme-linked immunosorbent assay (ELISA) (Genscreen ULTRA HIV Ag-Ab; Bio-Rad, Marnes-la-Coquette, France) and particle agglutination (SFD HIV 1/2 PA; Bio-Rad Fujirebio Inc., Tokyo, Japan).

Overall, 14.8% of the samples with discordant or indeterminate results were identified as HIV-positive using direct

diagnosis. With the identification of four new cases using the nucleic acid detection test, the HIV prevalence in MSM increased by 0.3% (from 10.4 to 10.7%). The results of this study suggest the importance of including nucleic acid detection in the HIV algorithm for MSM with HIV-indeterminate WB results and those with HIV-negative WB results and discordant results in screening assays, in order to decrease HIV transmission among this population with a high HIV prevalence and incidence. In Argentina, HIV diagnosis in adults follows the Centers for Disease Control and Prevention (CDC) recommendations which suggest antibody testing using one or two enzyme immunoassay tests (EIAs) and one confirmatory test [Western www.selleckchem.com/products/Etopophos.html blot (WB)] [1]. However, strategies limited to antibody testing may fail to detect infected individuals during early primary infection, with serious implications for public health. The early diagnosis of acute HIV infections may benefit patients by permitting clinical interventions, which Selleck Ganetespib can limit viral spread by decreasing viral loads and thus reducing the risk of transmission [2-4]. The most sensitive techniques to identify acute infections are based on the detection of viral nucleic acid by nucleic acid amplification testing (NAAT). Strategies

focused on pooled HIV RNA detection can be feasible and cost-effective. However, when the expected number of acute infections is high (as a consequence of high prevalence and incidence rates), use of this algorithm hinders the reporting of results on time and increases the overall cost of testing. In these cases, it is advisable to carry out individual nucleic acid testing. The first HIV prevalence study on men who have sex with men (MSM) from Buenos Aires revealed a rate of 13.8% [5]. The results of this study also showed that a large number of MSM (≈ 50%) were engaged in unprotected sexual

intercourse. A recent study conducted in MSM showed the same trend (HIV prevalence 10.4%; HIV incidence 6.3% persons/year) [6]. In order to decrease HIV transmission among MSM, it is necessary to improve early HIV diagnosis. almost Therefore, the general objective of this study was to contribute to reducing HIV transmission through the identification of HIV antibody-negative and NAAT-positive MSM during acute infection. A total of 1549 MSM were included in an HIV cross-sectional study conducted during 2006–2008 [6]. All the patients had to sign an informed consent form to participate in the study. HIV diagnosis was performed as described previously using two screening tests, an enzyme-linked immunosorbent assay (ELISA) (Genscreen ULTRA HIV Ag-Ab; Bio-Rad, Marnes-la-Coquette, France) and particle agglutination (SFD HIV 1/2 PA; Bio-Rad Fujirebio Inc., Tokyo, Japan).

The MAPT was designed to help prioritise patients on orthopedic waiting lists. Three groups were analyzed: patients who had no corticosteroid injection or aspiration, patients who received corticosteroid injections, and patients who received both joint aspiration with corticosteroid injections. Rapamycin cell line Results:  Patients who had both joint aspiration and injection reported an improvement in pain compared with those who had no injection (56.3%vs. 32.2%, P = 0.03). Those who had joint injections

also did better than those without injection (62.7%vs. 32.2%, P = 0.001). Reduced analgesia use was noted in 12.5% of patients with aspiration and injection compared with 1.7% with no injection or aspiration (P = 0.03). Improved walking distance was noted in 22.4% of patients who had injections compared with 8.5% of patients with no injections (P = 0.03). No significant differences in MAPT scores among the different treatment groups were noted. Conclusion:  This pilot study appears to show a beneficial trend in giving corticosteroid injections and to aspirate the knee in OA patients. Further studies are needed to address the mechanical PI3K Inhibitor Library mw benefits, quadriceps strengthening and pain reduction with knee aspiration, as well as the effects that different volumes of fluid may have on knee mechanics and symptoms. “
“Magnetic resonance imaging (MRI) has added

a new dimension to the study of osteoarthritis, a long-known degenerative joint disease with limited therapeutic options. It has advanced our understanding of joint pathophysiology and identifying that osteoarthritis as a simple ‘wear and tear’ process of the articular cartilage has indeed become a thing of the past. Recent work has focused on the study and validation of MRI scoring/quantification systems, as well as the identification of MRI predictors of symptoms/disease progression. The latter may serve to identify patients at greater risk for osteoarthritis disease progression to be enrolled in clinical trials. Like all imaging tools, MRI use has its associated problems. Structural changes seen in patients with osteoarthritis are often seen in asymptomatic subjects

and this makes an MRI definition of osteoarthritis less straightforward. The ability to pick up multiple structural filipin abnormalities simultaneously and high sensitivity in delineating structural changes can makes interpretation of true pathology more complicated. Although there has been much progress in the field of MRI in osteoarthritis, there remain many clinical/technical issues that need to be addressed. Until more data are obtained from clinical trials, the question of whether MRI is useful in therapeutics intervention in osteoarthritis remains unanswered. “
“Febuxostat, a novel non-purine selective inhibitor of xanthine oxidase, has been identified as a potential alternative to allopurinol in patients with hyperuricemia.

, 2010). However, knowledge of nitrogen metabolism and the genetic response

to nitrogen limitation in Mycobacteria selleck chemical is sparse. Mycobacterium tuberculosis, the aetiological agent of tuberculosis, remains a major public health problem (WHO, 2010) and is thought to experience many different environments including nutrient limitation during the establishment of infection. Therefore, understanding how mycobacteria coordinate and adapt to fluctuating supplies of nutrients such as nitrogen could identify the survival mechanisms required in tuberculosis infection. In Escherichia coli, the transcriptomic response to nitrogen limitation is well described, involving the NtrB/C two-component regulatory system directing the transcription

of approximately 100 genes (Zimmer et al., 2000). Mycobacterial genomes do not contain an NtrB/C homologue; instead the transcriptional response to nitrogen availability is thought to be mediated by the transcriptional regulator GlnR (Amon et al., 2008, 2009). The Mycobacterium smegmatis GlnR protein shares 55% amino acid identity with the GlnR response regulator of Streptomyces coelicolor (Amon et al., 2008), which regulates the expression of approximately 50 genes in response to nitrogen limitation (Tiffert et al., 2011); M. smegmatis (msmeg_5784) PTC124 manufacturer and M. tuberculosis (Rv0818) GlnR share 73% amino acid identity. Bioinformatics analysis identified known S. coelicolor GlnR DNA binding motifs in all available mycobacterial genomes (Amon et al., 2008). Furthermore, analysis of a M. smegmatis GlnR deletion mutant confirmed that during nitrogen limitation, GlnR positively regulates the transcription of glutamine synthetase, glnA1, and two ammonium transporters, amt1 and amtB (Amon et al., 2008). Interestingly, glnR transcription levels did not

significantly alter during nitrogen limitation, suggesting glnR transcription is not regulated in response to nitrogen availability, but rather GlnR activity is subject to an alternate control mechanism such as post-translational modification (Amon et al., 2008). Genomic analysis of nitrogen metabolism in mycobacteria (Amon et al., 2009) highlights several differences between Cetuximab concentration M. smegmatis and M. tuberculosis, with increased capacity for ammonium uptake in M. smegmatis and the lack of an apparent glutamate dehydrogenase in M. tuberculosis. This perhaps reflects the availability of nitrogen in the organisms’ natural environments, although their responses have not been compared directly. GlnR belongs to the OmpR family of two-component response regulators (Amon et al., 2008). Typically, OmpR-type response regulators are transcriptional activators, phosphorylated by a sensor kinase in response to extracellular stimuli (Kenney, 2002). A prominent feature of the OmpR family is a highly conserved aspartate residue, which undergoes phosphorylation by the sensor kinase.

polymyxa CCM 7400. The resulting PCR fragments indicated the presence of amplicons corresponding to a

448-bp fragment from a putative small terminase gene and a 405-bp fragment from a putative holin gene. The specificity of chosen PCR products was confirmed by DNA sequencing of the amplicons. We identified the presence of both 448- and 405-bp amplicon on the chromosomes of all tested isolates of P. polymyxa CCM 7400. We confirmed the presence of ΦBP DNA on the chromosome of P. polymyxa using Southern blot hybridization. The results of Southern blot analysis are shown in Fig. 5. On blotted samples of genomic click here DNA from P. polymyxa CCM 7400, we detected signals corresponding to those on bacteriophage ΦBP DNA using each of the three probes. The positions of hybridization signals on both chromosomal DNA and phage DNA were identical, suggesting that the restriction patterns of ΦBP sequences on the chromosome of P. polymyxa CCM 7400 are the same as those of ΦBP DNA. Superinfection with ΦBP of the clones positive for prophage presence resulted in lytic development in all cases, suggesting that ΦBP might be a virulent mutant phage. The primary aim of this work was to find out whether the occasional lysis of the growing culture of P. polymyxa is the result of bacteriophage infection. After successful isolation of phage particles, we extracted the phage DNA. We decided to clone and sequence eight EcoRI fragments

within 0.9–2.5 kbp. The results of bioinformatic analysis suggested the presence of some typical phage genes. We identified regions similar to a small and a large subunit of phage terminase genes and regions similar to

phage lytic ZD1839 genes. Both terminase and lytic genes Clomifene (especially the holin one) are exclusively phage genes and their presence confirmed our suspicion of phage infection. The next step of our work was to find out whether the bacteriophage ΦBP can lysogenize P. polymyxa. Using PCR amplification and Southern blot hybridization, we confirmed the presence of phage DNA on the chromosome of P. polymyxa CCM 7400. In many bacterial genomes, the bacteriophage DNA is integrated into the bacterial chromosome, where it represents a significant part of the total bacterial DNA. However, prophages are not only passive genetic elements. They serve as the vectors for horizontal gene transfer, influence virulence or fitness of bacteria and account for interstrain genetic variability in bacterial species (Canchaya et al., 2003). Prophages are valuable tools for evaluation of the diversity and identification of bacterial strains. Such experiments were also performed on Paenibacillus species exploiting bacteriophages IPy1 (dos Santos et al., 2002) and PPL1c (Stahly et al., 1999). We decided to study another member of the group of bacteriophages from paenibacilli, the phage ΦBP, in more detail. Along with the search for phage genes, we performed a study of the ΦBP propagation, its host spectrum and its life cycle.

1a, plate 5), ConA MG-132 reactivity of the Apa protein (Fig. 1b, lane 5 and c, lane 5), and in vitro labeling of polyprenyl phosphate (Fig. 2, lane 5). In mycobacteria and corynebacteria, Lnt and Ppm are either functional domains of the same protein (as in M. tuberculosis) or separate proteins encoded by contiguous genes that often exhibit translational coupling (Gurcha et al., 2002). All Streptomyces genomes sequenced to date reveal that the genes encoding Ppm are not preceded by those encoding homologues

of the Lnt domain of PpmMtu; instead, Streptomyces genomes show the presence of two genes encoding homologues of Lnt located separately on the chromosome. It has recently been shown in Streptomyces scabies that Lnt1, the homologue selleck chemicals exhibiting higher identity (44%) to Lnt of mycobacteria is functional, whereas the functionality of Lnt2, which exhibits only 26% identity, is still unclear (Widdick et al., 2011). We obtained a derivative of the wild-type J1928 with an in-frame deletion of the lnt1 gene (sco1014) and tested this strain (IB65, Table 1) for phage infection. Figure 3a (plate 3) and Table S2 show that φC31 was able to form plaques in the Δlnt1 mutant IB65; in addition, Apa protein obtained from this strain was recognized by ConA, indicating that it was glycosylated (data

not shown). Previous works have shown that the Lnt domain of PpmMtu is required for full Ppm activity and that it might anchor the catalytic domain (D2) to the membrane, in order to mannosylate the membrane polyprenyl phosphate (Gurcha et al., 2002). We therefore determined whether the PpmMtu D2 domain could complement the Δppm mutant in the absence Abiraterone in vivo of Lnt1. To do this, a double mutant was obtained with deletions of both the ppm and lnt1 genes (strain IB67, Table 1). Plasmids

expressing PpmSco (pBL13) or only the D2 domain of PpmMtu (pBL11) were introduced into the Δppm Δlnt1 mutant IB67 and analyzed for their ability to restore phage infection. Results shown in Fig. 3a and Table S2 reveal that, as expected, φC31 was unable to form plaques in IB67 (Fig. 3a, plate 4) and that plaque formation in the double mutant was restored by complementation with either PpmSco (Fig. 3a, plate 5) or the PpmMtu D2 domain (Fig. 3a, plate 6), meaning that Lnt1 is dispensable for Ppm activity in S. coelicolor. Given this observation and the difference in gene arrangement between streptomycetes and mycobacteria (Fig. S2), we asked whether the domain interaction previously reported between the D1 (Lnt) and D2 (Ppm) domains of PpmMtu (Baulard et al., 2003) was also shown by Lnt1 and PpmSco. To answer this, the S. coelicolor lnt1 and ppm genes were cloned in the bacterial two-hybrid system of Karimova et al.