All had fasting low-density lipoprotein (LDL) cholesterol ≤ 130mg

All had fasting low-density lipoprotein (LDL) cholesterol ≤ 130mg/dL. Seventy-eight per cent of patients were men and 65% were African-American. Median (interquartile range) age and CD4 count were 47 (43, 52) years and 648 (511, 857) cells/μL, respectively. All had HIV-1 RNA < 400 HIV-1 RNA copies/mL. Mean CCA-IMT BIBW2992 manufacturer was correlated with log-transformed CD8+CD38+HLA-DR+ percentage (r = 0.326; P = 0.043), and concentrations of interleukin-6 (r = 0.283; P = 0.028), soluble vascular cell

adhesion molecule (sVCAM; r = 0.434; P = 0.004), tumour necrosis factor-α receptor-I (TNFR-I; r = 0.591; P < 0.0001) and fibrinogen (r = 0.257; P = 0.047). After adjustment for traditional cardiovascular disease (CVD) risk factors, the association with TNFR-I (P = 0.007) and fibrinogen (P = 0.033) remained significant. Subjects with plaque (n = 22; 37%) were older [mean (standard deviation) 51 (7.7) vs. 43 (9.4) years, respectively; P = 0.002], and had

a higher CD8+CD38+HLA-DR+ percentage [median (interquartile range) 31% (24, 41%) vs. 23% (20, 29%), respectively; P = 0.046] and a higher sVCAM concentration [mean (standard deviation) 737 (159) vs. 592 (160) ng/mL, respectively; P = 0.008] compared with those without plaque. Pro-inflammatory monocyte http://www.selleckchem.com/products/ly2157299.html subsets and serum markers of monocyte activation (soluble CD163 and soluble CD14) were not associated with CCA-IMT or plaque. Participants in SATURN-HIV have a high level of inflammation and immune activation that is associated with subclinical vascular disease despite low serum LDL cholesterol. “
“The incidence of sexually transmitted hepatitis C virus (HCV) reinfection is on the rise in HIV-infected men who have sex with men (MSM). Data on natural history of acute

hepatitis C and possible factors associated with spontaneous clearance are limited. The Casein kinase 1 aim of this study was to analyse the outcome of HCV reinfections in HIV-positive MSM. A retrospective analysis was carried out on patients with more than one sexually acquired HCV infection who were diagnosed at four major German HIV and hepatitis care centres. Reinfection was defined by genotype or phylogenetic clade switch, detectable HCV RNA after a sustained virological response (SVR) or after spontaneous clearance (SC). In total, 48 HIV-positive MSM were identified with HCV reinfection, among them 11 with a third episode and one patient with four episodes. At the first episode, 43 and five patients had an SVR and SC, respectively. The second episode was accompanied by a genotype switch in 29 patients (60%). Whereas 30 and nine patients showed an SVR and SC, respectively, eight patients developed chronic hepatitis. Neither HCV genotype switch nor interleukin-28B genotype was associated with SC. However, SC rates at the second episode were higher for patients with SC at the first episode compared with patients without SC (60 vs. 14%, respectively; P = 0.03).

, 1963) It consists of two domains; a hydroxylase N-terminal dom

, 1963). It consists of two domains; a hydroxylase N-terminal domain with one molecule of noncovalently bound PQQ and Ca2+ at its active site as cofactors and a cytochrome c C-terminal binding domain with one covalently bound molecule of c-type haem which acts as an electron acceptor following lupanine dehydration (Hopper et al., 2002). Periplasmic targeting of the recombinant LH enzyme in Escherichia coli requires the co-expression of cytochrome c maturation factors and complex post-translational modifications that include signal peptide processing, covalent haem attachment to the C-terminal cytochrome c domain and putative disulphide bond formation

PD0325901 nmr (Stampolidis et al., 2009). Sequence analysis

with Clustal W (Larkin et al., 2007) reveals many common features of LH to members of the quinohaemoprotein family such as methanol dehydrogenase from Methylobacterium extorquens and particularly, ethanol dehydrogenase (EDH) from Comamonas testosteroni (Fig. 1). Some of the highly conserved residues among quinohaemoproteins involved in PQQ binding and at the active site of the enzyme are present Selleckchem Ku 0059436 in LH as is the invariant amino acid, Trp, which forms the floor of the active site cavity (Anthony, 1996; Hopper & Kaderbhai, 2003). In quinohaemoproteins, PQQ is usually sandwiched between a disulphide bond formed by two neighbouring Cys (Chen et al., 2002), for example, in methanol dehydrogenase 103,104Cys (Afolabi et al., 2001) and ethanol dehydrogenase 116,117Cys (Mennenga et al., 2009). The role of this bond is still a mystery. One hypothesis is that the disulphide bridge could potentially serve as an intraprotein redox centre, acting as a functional switch by relaying electrons from PQQ to the terminal acceptor in a similar manner to ferredoxin:thioredoxin reductase (Dai et al., 2000), glutathione reductase and lipoamide

dehydrogenase (White et al., 1993). A second theory claims that the bond could have a structural role for proper positioning of PQQ within the active site of the enzyme (Oubrie et al., 2002). However, LH possesses, in total, four Cys residues, two are part of the cytochrome c motif (586Cys and 589Cys), and the remaining two are separated by Methamphetamine 18 amino acids (124Cys and 143Cys). In this study, we attempted to establish the presence of the disulphide bond using chemical means and role in recombinant LH using site-directed mutagenesis with 143CysSer and 124,143CysSer mutations in E. coli. All chemicals were purchased from Sigma, Qiagen Ni-NTA agarose from Qiagen, and electrophoresis reagents were obtained from Bio-Rad and BDH (UK). Restriction enzymes and DNA-modifying enzymes were purchased from New England Biolabs and Promega (UK). Escherichia coli TB1 and pINK-LH-His4 construct were from Dr M. A. Kaderbhai Laboratory.

2c) No cleavage was observed when the XerSY314F mutant was used

2c). No cleavage was observed when the XerSY314F mutant was used instead of the wild-type protein (data not shown). The vector pBEA756 possesses both gram-positive thermosensitive (Ts) and ColE1 replication origins. An internal fragment of the S. suis xerS gene was generated by PCR and cloned into this vector, generating the plasmid pBEA756XerCint. This plasmid was then successfully introduced into S. suis by electroporation

as described in section ‘Growth conditions and DNA manipulations’. At the restrictive temperature (37 °C), homologous recombination events were selected for by maintaining growth in the presence of kanamycin. Torin 1 molecular weight A single crossover event between the cloned xerS gene on the plasmid and the chromosomal copy of xerS resulted in the inactivation of the xerS gene, which was confirmed by PCR and by Southern blot (data not shown). Microscopic analysis of xerS mutant cells showed a significant increase in average chain length, with most of wild-type cells being 5–10 cells long, while mutants were more

than 10 cells long; in addition, extremely long chains, containing more than 30 cells, were also observed (Fig. 3). The re-introduction of a functional xerS with pGXerCF (pGhost9) restored the wild-type phenotype (data not shown). In this report, we described the purification and inactivation of the S. suis xerS gene and its MBP-fused product. The S. suis XerS recombinase was overexpressed and purified as a maltose-binding of protein fusion, as previous work with XerCD recombinases has indicated that the N-terminal MBP moiety has no significant effect on Xer binding, cleavage BI 6727 solubility dmso or strand transfer activity (Blakely et al., 1997, 2000; Neilson et al., 1999; Villion & Szatmari,

2003). The difSL site was located about 50 bp before the start of the xerS coding region, as was found for most of the lactococci and streptococci (Le Bourgeois et al., 2007). In addition, XerS of S. suis displays 70% identity and 82% similarity to XerS of Lactococcus lactis (Le Bourgeois et al., 2007). Specific binding of difSL was detected at MBP-XerS concentrations of 3.43 nM and above, in the presence of a 1000-fold molar excess of poly dIdC competitor (Fig. 1a). The observation of more than one complex suggests that MBP-XerS is binding to both half-sites of difSL, which is consistent with other systems using one recombinase like Flp and Cre. Binding to the left half-site was detected, while virtually no retarded bands were visible in reactions on the right half-site (Fig. 1b,c), in agreement with results found by Nolivos et al. (2010) on the lactococcal difSL site. The faster migrating bands correspond to the binding of a single XerS monomer on the DNA, while the slower migrating forms correspond to the binding of two or more XerS protomers on the DNA. The additional retarded complexes seen with the difSL left half-site are most likely additional monomers binding to the complex via protein–protein interactions.

The calibrated

The calibrated this website standard serum 89-SF was absorbed with 10 μg/mL CWPS. At least two internal controls were added to each plate. For serotypes 14 and 19F, a high-titre and a low-titre serum sample from

pneumococcal vaccine responders were used as internal controls, respectively. For serotype 23F, two high-titre and two low-titre serum samples from pneumococcal vaccine responders were used as internal controls. The coefficients of variation (CVs) for the high-titre controls were 19.53 and 16.55% for serotypes 14 and 19F and the CVs were 18.34 and 17.91% for serotype 23F. The CVs for the low-titre controls were 17.12 and 14.91% for serotypes 14 and 19F and the CVs were 15.39 and 14.23% for serotype 23F. Sera from persons with AIDS who had no antibodies to S. pneumoniae serotype 14, 19F, 23F or 6B capsules and <1 μg of antibody to CWPS per mL were used as negative controls. Capsular polysaccharides from S. pneumoniae serotypes 14 (catalogue number 197-X; lot #2038310), 19F (catalogue number 205-X; lot #2033178), 23F (catalogue number 217-X; lot #2048448) and 6B (catalogue number 225-X; lot #2045655) were obtained from the American

Type Culture Collection (ATCC; Manassas, VA, USA). These capsular polysaccharides were suspended in phosphate-buffered saline (PBS; pH 7.4) containing 0.02% NaN3 at a concentration of 10 μg/mL and used directly to coat wells

GSI-IX solubility dmso by incubation at 4 °C overnight. After washing of the antigen-coated plates, the pre-absorbed patient sera or controls were added to plates and incubated at room temperature for 2 h. After thorough washing to remove antibodies not bound to the wells, horseradish peroxidase (HRP)-conjugated goat antibody to human IgG (Zymed Laboratories Inc., San Francisco, CA, USA) at a dilution of 1:2000 was used to detect IgG, and the reaction was developed for 10 min in the dark by the addition of K-blue substrate (Neogen Demeclocycline Corporation, Lexington, KY, USA), followed by the addition of 1N sulphuric acid to stop the reaction. Between incubations, all washings were performed with Tris buffered saline (TBS) buffer containing 0.1% Brij solution. Optical density was read in an ELISA reader (SpectraMAX 340; Molecular Devices, Sunnyvale, CA, USA) at a wavelength of 450 nm, with subtraction of the optical density of the appropriate blank. The antibody concentrations were calculated relative to the 89-SF control serum, using the US Centers for Disease Control and Prevention (CDC) program elisa for Windows (version 2.15) [28]. The detection limits for our assay for 14, 19F, 23F and 6B, determined using the control serum 89-SF, were 0.02, 0.015, 0.02 and 0.50 μg/mL, respectively.

The calibrated se

The calibrated AZD6738 standard serum 89-SF was absorbed with 10 μg/mL CWPS. At least two internal controls were added to each plate. For serotypes 14 and 19F, a high-titre and a low-titre serum sample from

pneumococcal vaccine responders were used as internal controls, respectively. For serotype 23F, two high-titre and two low-titre serum samples from pneumococcal vaccine responders were used as internal controls. The coefficients of variation (CVs) for the high-titre controls were 19.53 and 16.55% for serotypes 14 and 19F and the CVs were 18.34 and 17.91% for serotype 23F. The CVs for the low-titre controls were 17.12 and 14.91% for serotypes 14 and 19F and the CVs were 15.39 and 14.23% for serotype 23F. Sera from persons with AIDS who had no antibodies to S. pneumoniae serotype 14, 19F, 23F or 6B capsules and <1 μg of antibody to CWPS per mL were used as negative controls. Capsular polysaccharides from S. pneumoniae serotypes 14 (catalogue number 197-X; lot #2038310), 19F (catalogue number 205-X; lot #2033178), 23F (catalogue number 217-X; lot #2048448) and 6B (catalogue number 225-X; lot #2045655) were obtained from the American

Type Culture Collection (ATCC; Manassas, VA, USA). These capsular polysaccharides were suspended in phosphate-buffered saline (PBS; pH 7.4) containing 0.02% NaN3 at a concentration of 10 μg/mL and used directly to coat wells

CDK inhibitor by incubation at 4 °C overnight. After washing of the antigen-coated plates, the pre-absorbed patient sera or controls were added to plates and incubated at room temperature for 2 h. After thorough washing to remove antibodies not bound to the wells, horseradish peroxidase (HRP)-conjugated goat antibody to human IgG (Zymed Laboratories Inc., San Francisco, CA, USA) at a dilution of 1:2000 was used to detect IgG, and the reaction was developed for 10 min in the dark by the addition of K-blue substrate (Neogen selleck chemical Corporation, Lexington, KY, USA), followed by the addition of 1N sulphuric acid to stop the reaction. Between incubations, all washings were performed with Tris buffered saline (TBS) buffer containing 0.1% Brij solution. Optical density was read in an ELISA reader (SpectraMAX 340; Molecular Devices, Sunnyvale, CA, USA) at a wavelength of 450 nm, with subtraction of the optical density of the appropriate blank. The antibody concentrations were calculated relative to the 89-SF control serum, using the US Centers for Disease Control and Prevention (CDC) program elisa for Windows (version 2.15) [28]. The detection limits for our assay for 14, 19F, 23F and 6B, determined using the control serum 89-SF, were 0.02, 0.015, 0.02 and 0.50 μg/mL, respectively.

, 1997), both of the pathways for nitrate reduction to ammonia ar

, 1997), both of the pathways for nitrate reduction to ammonia are expressed only during anaerobic growth. Transcription of narGHJI and

nirBD is also activated by the NarX-NarL two-component regulatory system in response to moderate concentrations of nitrate; nirBD, and to a much lesser extent narGHJI, are also activated by the alternative two-component system, NarQ-NarP (Rabin & Stewart, 1993). Classical genetic approaches and more recent whole genome transcriptomic studies have indicated that the cytoplasmic pathway is physiologically more significant only in nitrate-rich environments that might occur in soil, in some highly contaminated sediments, and waste water treatment plants (Potter et al., 1999). In contrast, the transcription of genes for the periplasmic Nap-Nrf pathway Wnt inhibition is activated by NarQ-NarP in response to low concentrations of nitrate (< 100 μM) click here but are repressed by NarX-NarL when nitrate is abundant (Page et al., 1990).

This indicates that the periplasmic pathway confers a selective advantage for bacterial survival in the nitrate limited environment of the gastro-intestinal tract of humans and other warm blooded animals (Potter et al., 1999; Constantinidou et al., 2006). Based upon the accumulation of very small quantities of nitrous oxide during nitrite reduction, it was assumed that the rate of NO production was two to three orders of magnitude slower than the rate of nitrite reduction (Smith, 1983).

It was predicted that NO was a side product released during science nitrite reduction by either NirBD or NrfA. However, there is an extensive literature showing that the major source of nitrosative stress is NO generated by the interaction of the cytoplasmic nitrate reductase, NarG, with nitrite (reviewed in the accompanying paper by Vine et al., 2011). Realization that enteric bacteria can reduce nitrite to NO re-opened the question whether NO is generated by a single mechanism or by more than one pathway, depending on the conditions under which the bacteria are grown. Specifically, is more NO generated by the membrane-associated nitrate reductase, NarG, by one of the nitrite reductases, NirBD or NrfAB, or by other molybdoproteins that are active during anaerobic growth? The sensitive response of the transcription repressor, NsrR, to NO provides a method to detect the presence of NO in the bacterial cytoplasm (Hutchings et al., 2000; Corker & Poole, 2003; Bodenmiller & Spiro, 2006; Tucker et al., 2008). By coupling an NsrR-regulated E. coli promoter to lacZ expression during anaerobic growth in the presence of nitrite, it was shown that mutations in nirBD or nrfAB resulted in greater expression of lacZ, indicative of the increased accumulation of NO in the cytoplasm (Vine et al., 2011). Conversely, deletion of the narGHJI operon significantly decreased but did not eliminate lacZ expression, indicative of less accumulation of cytoplasmic NO.

Arousal was not formally assessed in our study, eg by scores or

Arousal was not formally assessed in our study, e.g. by scores or skin conductance responses. Therefore, we cannot make judgements regarding the level of arousal. However, the fact that there was a matching in the behavioural results of the tasks does aid the interpretation of the motor data in that any differences seen for the two behavioural conditions are a consequence of differences relating to underlying processes in performing them (presumably related to the differences in external and internal attention) rather than potentially a result of different associated difficulties. Whatever

the final explanation, the results are of relevance to a number of different disorders. As noted in the Introduction, focal dystonia often appears to be associated with the repeated performance of movements made under conditions of highly focussed attention, selleck chemicals such as occur in professional musicians. Indeed, attention is an important part of learning. However, too great a focus on one area may reduce inhibitory control in other areas and potentially contribute to an overflow of activity. In healthy individuals, this is often seen in the early phases of learning a see more new skill, but this is gradually reduced as learning progresses. It may that this natural process is defective in focal dystonia and leads to the persisting and unwanted activity characteristic

of the condition. It is remarkable how widespread is the range of disorders that involve abnormal SICI, e.g. dystonia (Sommer et al., 2002), Tourette’s syndrome (Orth & Rothwell, 2009), and first-episode schizophrenia (Wobrock et al., 2008). The interpretation tends to be that intracortical GABAA circuits per se are impaired. The

current study demonstrates a modulation towards a reduced amount of SICI when healthy participants pay attention to an internal or external locus. Therefore, the reduced inhibition seen in so many disorders might, in some cases, be explained by differences in cognitive states (attention state) rather than being a genuine physiological marker. A practical relevance of the present results seems more striking. High levels of attention are required for learning that interacts with synaptic plasticity processes (Ziemann et al., 2004). Behavioural data are supported by experimental methods that demonstrate the Idoxuridine interaction between attention and plasticity-inducing protocols (Stefan et al., 2004) that are facilitated by directing the subject’s attention to their own hand. This might be mediated via the fine tuning of inhibitory and excitatory circuits in the M1. A necessity of all goal-directed movements is the right balance between inhibiting and facilitating components. To reach an overall economical activation it is vital to be able to relax, for example, antagonistic muscles. The playing-related health problems of musicians are often the end-stage of suboptimal learning processes.

Arousal was not formally assessed in our study, eg by scores or

Arousal was not formally assessed in our study, e.g. by scores or skin conductance responses. Therefore, we cannot make judgements regarding the level of arousal. However, the fact that there was a matching in the behavioural results of the tasks does aid the interpretation of the motor data in that any differences seen for the two behavioural conditions are a consequence of differences relating to underlying processes in performing them (presumably related to the differences in external and internal attention) rather than potentially a result of different associated difficulties. Whatever

the final explanation, the results are of relevance to a number of different disorders. As noted in the Introduction, focal dystonia often appears to be associated with the repeated performance of movements made under conditions of highly focussed attention, Trametinib solubility dmso such as occur in professional musicians. Indeed, attention is an important part of learning. However, too great a focus on one area may reduce inhibitory control in other areas and potentially contribute to an overflow of activity. In healthy individuals, this is often seen in the early phases of learning a PF2341066 new skill, but this is gradually reduced as learning progresses. It may that this natural process is defective in focal dystonia and leads to the persisting and unwanted activity characteristic

of the condition. It is remarkable how widespread is the range of disorders that involve abnormal SICI, e.g. dystonia (Sommer et al., 2002), Tourette’s syndrome (Orth & Rothwell, 2009), and first-episode schizophrenia (Wobrock et al., 2008). The interpretation tends to be that intracortical GABAA circuits per se are impaired. The

current study demonstrates a modulation towards a reduced amount of SICI when healthy participants pay attention to an internal or external locus. Therefore, the reduced inhibition seen in so many disorders might, in some cases, be explained by differences in cognitive states (attention state) rather than being a genuine physiological marker. A practical relevance of the present results seems more striking. High levels of attention are required for learning that interacts with synaptic plasticity processes (Ziemann et al., 2004). Behavioural data are supported by experimental methods that demonstrate the click here interaction between attention and plasticity-inducing protocols (Stefan et al., 2004) that are facilitated by directing the subject’s attention to their own hand. This might be mediated via the fine tuning of inhibitory and excitatory circuits in the M1. A necessity of all goal-directed movements is the right balance between inhibiting and facilitating components. To reach an overall economical activation it is vital to be able to relax, for example, antagonistic muscles. The playing-related health problems of musicians are often the end-stage of suboptimal learning processes.

4%), C18:1 ω7c (198%), and C16:0 (170%) The DNA G + C content

4%), C18:1 ω7c (19.8%), and C16:0 (17.0%). The DNA G + C content was 48.6 mol%. The 16S rRNA gene sequence analysis indicated that strain KU41ET is affiliated with the order Alteromonadales within the class Gammaproteobacteria and is most closely related to Pseudoteredinibacter isoporae SW-11T (93.6% similarity) and Teredinibacter turnerae T7902T (91.9% similarity). On the basis of physiological, chemotaxonomic, and phylogenetic data, strain KU41ET is suggested to represent a novel species of a new genus, for which the name Maricurvus nonylphenolicus gen. nov., sp. nov. is proposed. The type strain of M. nonylphenolicus is KU41ET (=JCM 17778T). Contamination of the marine

environment with alkylphenols is of great public concern because of their toxicity and endocrine disrupting activity in humans and marine organisms (David et al., 2009). A number of alkylphenol-degrading AZD9291 order bacteria have been isolated and characterized (Fujii et al., 2001; Ushiba et al., 2003), and the mechanism for alkylphenol degradation has been studied extensively (Corvini et al., 2006; Takeo et al., 2006; Porter & Hay, 2007). However, these Y27632 organisms have mainly been isolated from terrestrial or freshwater sites, and information regarding alkylphenol-degrading bacteria from marine environments is relatively scarce. Here, we report on the isolation and characterization of a novel

marine p-n-nonylphenol-degrading bacterium, strain KU41ET. Comparative 16S rRNA gene sequence analysis indicated that strain KU41ET forms an independent branch within Gammaproteobacteria. Accordingly, the aim of the present work was to determine the exact taxonomic position of strain KU41ET by a polyphasic characterization that included Bortezomib supplier phenotypic and chemotaxonomic properties and detailed phylogenetic analysis based on the 16S rRNA gene sequence. A p-n-nonylphenol-degrading bacterial strain

designated KU41ET was isolated from seawater collected from the coastal region of Ishigaki Island in Japan in December 2009. Marine bacteria were collected from 1 L of the seawater sample by filtration using the membrane filters (diameter 47 mm, pore size 0.45 μm; Nihon Millipore) and then suspended in 3 mL of the commercial artificial seawater medium Daigo’s IMK-SP, which was made by dissolving 252 mg of IMK medium in 1 L of Daigo’s Artificial Seawater SP (Nihon Seiyaku). A 1-mL suspension of the sample was inoculated into 4 mL of Daigo’s IMK-SP supplemented with 10 mM p-n-nonylphenol and incubated at 25 °C on a rotary shaker at 100 r.p.m. After 7 days of enrichment, 4 μL of the culture medium was transferred into a fresh medium and incubated for seven more days. The enriched culture was plated on the same medium solidified with 1.5% (w/v) agar, and the strain was purified by transferring the colony several times onto fresh agar plates. To completely isolate the p-n-nonylphenol-degrading bacterium, a colony was transferred onto a plate of Marine Agar 2216 (MA; Becton Dickinson).

1 and the possible significance of the histidine-rich C-terminal

1 and the possible significance of the histidine-rich C-terminal tail in selecting these polypeptide substrates. In

GroEL, the C-terminal tail is highly flexible and thus undefined in the crystal structures (Hartl & Hayer-Hartl, 2002; Machida et al., 2008). However, a detailed genetic analysis of the final 23 residues assessing the ability of C-terminal-truncated, double- and single-ring mutants to assist the refolding of rhodanese and malate dehydrogenase showed that this domain defines the environment within the central cavity and in particular its hydropathicity, features that would impact on both the size and nature of the substrate protein folded by the chaperonin (Tang et al., 2006; Machida et al., 2008). This is consistent with a role for the mycobacterial Cpn60.1 click here chaperonins in the folding EPZ-6438 supplier of a distinct class of proteins, possibly unique to mycobacteria or actinomyces. Although a distinct DNA-bound function in the assembly of the nucleoid has recently been proposed for Cpn60.1 (Basu et al., 2009) this is unlikely to involve the C-terminal tail sequence, as the mitochondrial Hsp60 chaperonin for which nucleotide binding has also been reported does not have a histidine-rich C-terminal tail (Kaufman et al., 2003; Basu et al., 2009). A database search with the histidine-rich C-terminal sequence of Cpn60.1 reveals highly homologous proteins across

all mycobacterial species, as well as Corynebacteria, Nocardia and Rhodococcus (C. Colaco, unpublished data). A common feature of all these Actinobacteria is their synthesis of a complex cell wall containing mycolic acid derivatives, and this suggests the intriguing possibility that the biological role of the mycobacterial Cpn60.1 may be to chaperone the folding of key enzymes involved in the synthesis Fossariinae of mycolic acid. Such a role for Cpn60.1 is also consistent with the defects

in mycolates and biofilm formation observed in the cpn60.1 knockouts in M. smegmatis, where the protein was also found to be associated with KasA and SMEG4308, both key enzymes implicated in biofilm formation and involved in fatty acid synthesis (Tang et al., 2006; Kumar et al., 2009). In this respect, it is interesting to note that the oligomerisation of Cpn60.1 has been shown to be facilitated by phosphorylation (Canova et al., 2009), which is thought to be mediated by the serine threonine protein kinases that have also been implicated in biofilm formation (Gopalaswamy et al., 2008). Finally, as KasA has been identified as an important drug target for the development of new drugs against TB (Brown et al., 2009), the most interesting implication of the suggested role of Cpn60.1 is that this novel mycobacterial chaperonin may present an upstream target for drug development. Thus, therapeutics that target Cpn60.