The emergence of CA-MRSA clones in different MLST clonal clusters

The emergence of CA-MRSA Selleckchem Mdivi1 clones in different MLST clonal clusters indicates Selleck Tideglusib horizontal transmission of the SCCmec element into S. aureus has occurred on at least five occasions in these remote communities: SCCmec IVa [2B] into CC1 (ST1), CC5 (ST5), CC8 (ST8), CC88

(ST78), and SCCmec V [5C2] into CC45 (ST45). Based upon the spa type and the DNA microarray profile at least six evolutionary events have occurred on at least three occasions from these clones (ie vertical transmission of the SCCmec element): twice from WA1, WA3 and WA5 (Figure 2). Vertical transmission of the SCCmec element has not been identified for WA4 or WA2. Figure 2 Proposed evolution of CA-MRSA from WA-1 (ST1-MRSA-IV), WA-3 (ST5-MRSA-IV) and WA-5 (ST8-MRSA-IV). The emergence of WA1, WA2 and WA3 has been due to the acquisition and insertion of the small and highly mobile type IVa [2B] SCCmec element, presumably harbored by methicillin resistant coagulase negative staphylococci (MRCNS). Several hypotheses to explain the transmission of a SCCmec element from MRCNS to S. aureus have been proposed including the increased use of antimicrobials within a community [35]. Many

of the Kimberley indigenous population live in poor socioeconomic conditions. Staphylococcal Temsirolimus mw skin lesions, commonly resulting from scabies infestation, trachoma and venereal diseases such as chlamydia and gonorrhea occur frequently in this population. Consequently empirical therapy using β-lactamase stable penicillins and azithromycin is often prescribed [36]. The frequent use of these antimicrobials may have assisted in the acquisition of the SCCmec element and erm genes into S. aureus. Genetic studies however have shown these newly emerged CA-MRSA clones did not originate in the predominant methicillin-susceptible S. aureus (MSSA) clones found in these communities, suggesting not all clones are able

to acquire or retain the SCCmec element [37]. The subsequent dissemination of WA1, WA2 and WA3 into the wider community suggests the acquisition of the SCCmec element and the erm genes has given these clones a selective Etomidate advantage. WA4 and WA5 however have not been successful in spreading beyond the indigenous communities suggesting the acquisition of the SCCmec element does not provide a universal selective advantage. Many of the remaining 46 CA-MRSA clones, identified between July 2003 and June 2010, were not isolated in remote WA indigenous communities. The geographical spread of CA-MRSA over long distances and across cultural borders is believed to be a rare event compared to the frequency in which the SCCmec element is acquired by S. aureus [38]. Most of these clones are therefore likely to have evolved in WA. Some clones are slvs and dlvs of pre-existing CA-MRSA, and their SCCmec type, spa type and DNA microarray profile suggests vertical transmission of the SCCmec element has occurred.

It is safe to say that there is no consensus regarding the

It is safe to say that there is no consensus regarding the optimal choice Tucidinostat manufacturer of method

when one VS-4718 clinical trial considers additionally the prediction of energies for electronically distinct states of the same species, such as those arising from different electronic configurations of a metal center, from a different distribution of oxidation states within a metal cluster, or even from the interplay between metal-centered and ligand-centered redox processes. When these factors come into play, the error margin can easily exceed by far the optimistic range mentioned earlier. Nevertheless, even if the estimated errors may be already too large for quantitative predictions in cases of small activation energies such as those observed during the catalytic cycle of the OEC (Sproviero et al. 2007), the simulation of reaction pathways is a fundamentally important application of DFT. A representative example that stands out in the field of photosynthesis research is the systematic work that has been focused on elucidating mechanistic aspects in the catalytic cycle of OEC (Lundberg and Siegbahn 2004; Siegbahn 2006a, 2008a, b; Sproviero et al. 2008a,

b). This line of work demonstrates that DFT calculations can offer significant input to mechanistic investigations, CA4P purchase sometimes revealing possibilities that were not previously considered. It should be kept in mind, however, that a reaction mechanism predicted by DFT cannot be validated on the basis of computed energies alone, especially when the structure of the principal component is itself debatable. All such efforts should attempt to combine and incorporate many lines of evidence, taking into account additional criteria such as the spectroscopic properties

of the putative intermediates. Vibrational frequencies Closely connected in research practice to the procedure of structural optimization is the calculation of vibrational frequencies. They are used not only for simulating infrared (IR) or Raman spectra but CYTH4 also for characterizing the nature of stationary points as minima or transition states. Moreover, the information obtained from such a calculation is used to compute statistical thermodynamic corrections to the electronic energy and thus to make direct comparisons with experimentally determined free energies. It is well established that the predicted harmonic frequencies with GGA functionals such as BP86 and PBE typically agree well with measured vibrational fundamentals if basis sets of polarized triple-ζ quality are used (Murray et al. 1992; Sosa et al. 1992; Stratmann et al. 1997).

0 1 (Bio-Rad) Comparative 2DE data were derived from 4 separate

0.1 (Bio-Rad). Comparative 2DE data were derived from 4 separate protein preparations, each one obtained from independent cultures. The spots were quantified on the basis of their relative ‘volume’: the amount of a protein spot was expressed as the sum of the

intensities of all the pixels that made up the spot. To compensate for subtle differences in sample loading, gel staining and de-staining, the volume of each spot was normalized in relation to the total density of valid spots present in the gel image. After automated detection and matching, manual editing was carried out. To determine the experimental pI and M r coordinates for each single protein spot, 2DE gels were calibrated using a selected set of five protein landmarks distributed throughout the gel. Protein digestion, peptide extraction selleck screening library and MS/MS analysis In-gel digestion of 2DE separated protein Volasertib nmr spots was carried out essentially as described [86]. Briefly, protein spots were excised and the gel pieces washed 3 times with 50% (v/v) acetonitrile (ACN) in 25 mM ammonium bicarbonate for 15 min each,

dehydrated in ACN, and dried in a vacuum centrifuge. Gel pieces were rehydrated in 15 μl of 50 mM ammonium bicarbonate containing 200 ng of sequencing grade C646 manufacturer modified trypsin (Promega). This step was performed for 40 minutes at 4°C and, after that, 20 μl of 50 mM ammonium bicarbonate were added to keep the gel pieces wet during tryptic digestion (37°C, 16 h). To extract peptides, 20 μl of 0.5% (v/v) trifluoroacetic acid (TFA) in 50% (v/v) ACN were added and samples were sonicated 3 times for 10 min each in a sonicator bath. The supernatant was recovered and concentrated under vacuum to a volume of approximately 10 μl. The resulting peptides were extracted, partially

dried, and salts were removed using C18 ZipPlate (Millipore, Bedford, MA) following the manufacturer’s instructions. The tryptic peptides were analyzed in a 4700-Proteomics nearly Analyzer MALDI-TOF/TOF (Applied Biosystems, Foster City, CA). All mass spectra were acquired on positive ion reflector mode with 2,000 shots per spot and externally mass calibrated with a peptide mixture. The 10 most intense ion peaks from the peptide mass fingerprinting (or MS run) were further submitted to fragmentation using PSD mode with CID gas off and 1 keV collision energy. Protein identification Following MS acquisition, each spectrum was submitted to a peptide mass fingerprinting search, in the case of MS/MS spectra, using Mascot version 2.2 (Matrix Science – http://​www.​matrixscience.​com/​ ). For protein identification, the search was performed against the NCBI-nr non-redundant database (NCBI-nr200709, National Center for Biotechnology Information, http://​www.​ncbi.​nlm.​nih.​gov/​) without taxonomy restriction. When necessary, further searches were performed against the Mycobacterium tuberculosis database (http://​genolist.​pasteur.​fr/​tuberculist).

However,

in the present work, no evidence of Er reductive

However,

in the buy PFT�� present work, no evidence of Er reductive peaks was found in the cyclic voltammetries carried out on pristine PSi layers in the same range of potentials (data not shown). Moreover, a jelly-like phase, constituted by Er ethanolate, has been observed following Er doping with similar parameters [14]. The presence of this jelly-like phase within the pores and the proportionality of the rate of the deposit formation to the current density have also been reported [13]. On the basis of these results, a possible interpretative model of the observed selleck kinase inhibitor behavior can be proposed: the applied electric field induces a migration of the Er3+ ions present in the electrochemical solution towards the inner pores surface, so generating a distribution of charges inside the pores, as well as a charge transfer of the ions inside of the solid structure. These two processes originate two resistive/capacitive responses in the

GEIS spectra (second and third circles in Figure 4a,b). At high electric fields, the high ion flux in the liquid phase leads to a consistent Er3+ ion accumulation near the PSi surface up to a concentration high enough for the formation of the jelly-like layer, and in turn, a new interphase appears, originating the last semicircle in the spectra of Figure 4b.Finally, in order to derive information on the onset of the transients observed at different current doping, GEIS measurements were carried out applying different constant bias current densities, Galunisertib matching those used for the continuous doping of the samples of Figure 1. For each sample, a series of GEIS spectra were recorded, starting from the pristine Adenosine PSi layer, so to follow the behavior observed for the continuous doping. In fact, since each GEIS cycle is identical to the others, we can assimilate the series of GEIS cycles to a sort of step-by-step doping.Figures 5 and 6 show some examples of the GEIS results, in terms of Nyquist diagram, performed on nominally identical samples using different constant bias currents (indicated in each figure). Each curve of a graph corresponds

to a single GEIS cycle, and each point on a GEIS cycle is obtained at a single frequency. The first cycle in each series is at the bottom and the last at the top. Please note that the graphs of Figure 4 are the 4th and 3rd GEIS cycles of Figures 5a and 6b, respectively.The difference of the GEIS measurements results in Figures 5 and 6 is evident, and we associate the behavior shown in Figure 5 to the ST regime (lower currents) and the one in Figure 6 to the DT regime (higher currents). Figure 5 Examples of GEIS results for low doping current intensities. Evolution in time of Nyquist plots during the Er doping of two nominally identical PSi samples, 1.25 μm thick, carried out at low current intensities (I = +0.010 mA for a and I = +0.015 mA for b).

A reduction in the expression of comX by carolacton after CSP sti

A reduction in the expression of comX by carolacton after CSP stimulation could therefore be caused by a direct interaction of carolacton with ComD, with CSP, or with the binding of CSP to ComD, resulting in an impaired signaling cascade and reduced comX expression. Since a ΔcomD mutant, which cannot respond to CSP through ComD, shows only slightly reduced sensitivity to carolacton, this scenario is not supported by the data. It appears more likely that one of the other two-component systems involved in competence regulation or stress response is inhibited by carolacton, and that this inhibition is relayed to comX via the specific signaling cascade. The comD gene was shown to be differentially expressed

in a RR11 mutant [47], and therefore an indirect effect of carolacton on comD expression through one of the other two-component systems is also possible.

Other mechanisms could also contribute to cell Osimertinib clinical trial death in a growth dependent way. For example, the gene atlA was discovered to decrease autolysis and cause elongated cell chains, thus affecting biofilm formation [49, 50]. Interestingly, the ΔcomD mutant, which is unable to induce comX expression after CSP stimulation, was slightly less sensitive to carolacton, but carolacton reduced the CSP induced comX expression, which appears to be contradictory. However, the sigma factor comX and the histidine kinase comD are connected through a complex signaling network which receives input from several histidine kinases as well as additional regulators. The experimental conditions analysed here, e.g. knock-out of comD, and determination Selleckchem GS-9973 of comX expression after CSP stimulation, both are highly artificial. Thus, since the mechanism of carolacton is not known, the causal relationship between them cannot be inferred from the data presented here. ComD plays apparently only a small role for the (-)-p-Bromotetramisole Oxalate effect of carolacton. If one or several of the other thirteen two-component systems of S. mutans are affected by carolacton, this could lead to the observed result with the highly sensitive pcomX reporter strain. A transcriptome analysis would be needed to determine the effect of carolacton on

comD and comX expression as well as on the other two-component systems of S. mutans under “”natural”" conditions, d.h. without additional stimulation by CSP. CSP has been shown to inhibit biofilms and to cause elongated cells at high concentrations [33]. Antibacterial activity of other peptides has been tested against S. mutans, but relatively high concentrations are required [51]. Killing activity was therefore enhanced by a combination of inhibitory peptides with desinfectants [52]. Killing activity has also been enhanced by constructing synthetic peptides consisting of two inhibitory domains [53]. In another approach, the cytotoxic effect of inhibitory peptides was combined with the specificity of the ComD receptor, resulting in so called STAMPs (targeted LOXO-101 nmr antimicrobial peptides).

The precipitation of hydrazide 3 was filtered, dried, and

The precipitation of hydrazide 3 was filtered, dried, and crystallized from ethanol. Yield: 91.4 %, mp: 196–198 °C (dec.). Analysis for C16H15N5OS (325.39); calculated: C, 59.06; H, 4.65; N, 21.52; S, 9.82; found: C, 59.10; H, 4.63; N, 21.49; S, 9.78. IR (KBr), ν (cm−1): 3105 (CH Foretinib aromatic), 2980, 1423 (CH aliphatic), 1698 (C=O),

1611 (C=N), 1522 (C–N), 699 (C–S). 1H NMR (DMSO-d 6) δ (ppm): 3.91 (s, 2H, CH2), 4.31 (s, 2H, NH2), 7.31–7.57 (m, 10H, 10ArH), 9.40 (brs, 1H, NH). Derivatives of thiosemicarbazide (4a–l) General method (for compounds 4a–l) A mixture of 3.25 g (10 mmol) of hydrazide (3) and 10 mmol appropriate isothiocyanate was heated in an oil bath at 50–110 °C for 8–20 h. The product was washed with learn more diethyl ether to remove unreacted isothiocyanate. Then it was filtered, dried, and crystallized from ethanol 4a–c, d, g–l, butanol 4e, or methanol 4f. Method B (for compounds 4a, c, d) 10 mmol of appropriate isothiocyanate

was added to 3.25 g (10 mmol) of hydrazide 3 in 10 mL of anhydrous diethyl ether. The mixture, placed in a conical bulb, was mixed for 5 min and left in room temperature for 24 h. The precipitation of thiosemicarbazide 4a, c, d was filtered, dried, and crystallized from ethanol. The obtained compounds had the same melting points as the compounds obtained by the general method. 4-Ethyl-1-[(4,5-diphenyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetyl thiosemicarbazide (4a) Yield: 94.0 %. Temperature of reaction: 70 °C

for 8 h, mp: 205–207 °C (dec.). Analysis for C19H20N6OS2 (412.53); selleck compound calculated: C, 55.32; H, 4.89; N, 20.37; S, 15.54; found: C, 55.23; H, 4.88; N, 20.43; S, 15.59. IR (KBr), ν (cm−1): 3199 (NH), 3101 (CH aromatic), 2974, 1453, 741 (CH aliphatic), 1699 (C=O), 1607 (C=N), 1519 (C–N), 1329 (C=S), 691 (C–S). 1H NMR (DMSO-d 6) δ (ppm): 1.12 (t, J = 9 Hz, 3H, CH3), 3.51–3.60 (q, J = 7.5 Hz, J = 7.5 Hz, 2H, CH2), 3.90 (s, 2H, CH2), 7.34–7.57 (m, 10H, 10ArH), 8.32, 9.33, 10.25 (3brs, 3H, 3NH). 13C NMR δ (ppm): 14.61 (CH3), 30.75 (–S–CH2–), 33.90 (–CH2–CH3), 126.42, 127.68, selleck 127.95, 128.79, 130.07, 130.11 (10CH aromatic), 130.33, 133.65 (2C aromatic), 152.08 (C–S), 154.59 (C-3 triazole), 166.82 (C=O), 181.23 (C=S). MS m/z (%): 412 (M+, 2), 397 (3), 335 (2), 325 (5), 294 (26), 253 (61), 252 (100), 194 (21), 180 (20), 149 (20), 118 (23), 104 (25), 91 (44), 77 (79). 4-Allyl-1-[(4,5-diphenyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetyl thiosemicarbazide (4b) Yield: 90.7 %. Temperature of reaction: 55 °C for 12 h, mp: 192–194 °C (dec.). Analysis for C20H20N6OS2 (424.54); calculated: C, 56.58; H, 4.75; N, 19.79; S, 15.10; found: C, 56.53; H, 4.76; N, 19.81; S, 15.14.

The ETGA AST method was successful in producing MICs that were in

The ETGA AST method was successful in producing MICs that were in agreement with results obtained from the macrobroth dilution method using bacteria harvested directly from positive blood cultures. In contrast, gsPCR was less successful: MRSA versus oxacillin produced a very major

error at six hours, and MRSA versus vancomycin produced gsPCR reactions that were not always detected. A point of concern with these experiments is that the inoculation verification indicated that the bacterial input was much lower than 5E + 05 CFU/mL because the CFU were too dilute to be countable. It has been reported that a 0.5 McFarland standard, which is expected to be within 1-2E + 08 CFU/mL may be as low as 1E + 07 CFU/mL depending CP-868596 nmr on the species being measured [3]. While this lower titer appeared not to affect the macrobroth or the ETGA results, it may have affected the gsPCR results. The procedure for harvesting the bacteria with a SST was followed as described by Beuving et al. [19, 20]. However, their manuscripts do not indicate whether the investigators verified their inoculation concentration performing their molecular AST assays. Harvesting

bacteria with SST from positive blood cultures Proteases inhibitor was previously described by Funke and Geneticin cost Funke-Kissling [13] for gram negative rods, and by Lupetti et al. [14] for gram positive cocci. In these reports, gram negative rods were harvested by applying positive blood culture directly into an SST, but gram positive cocci were first incubated in a 0.01% final concentration of saponin. The report from Beuving et al. harvests bacteria through an SST without any pre-treatment regardless of the gram status. If pre-treatment of the blood culture before serum separation is required for a more efficient bacterial yield, particularly for gram positive cocci, this could be a reason for some of the errors that we observed. Furthermore, we noticed that Thalidomide transferring

bacteria from the gel plug to the saline solution can also lead to transferring some of the gel which could lead to overestimating the turbidity of the 0.5 McFarland standard. This observation presents an opportunity to further improve the sample preparation for increased bacterial yield harvested directly from positive blood cultures and ultimately improve the accuracy of molecular AST. Wiegard et al. [7] describe a microdilution AST method performed in a 96-well microtiter plate. The authors present a protocol in which a bacterium of interest is inoculated into a matrix of various antibiotics and concentrations. This plate is incubated for 16–20 hours prior to interpreting the results by visual observation. Utilizing this design, a high-throughput ETGA AST method could be developed. In this scenario, an AST matrix can be assembled (keeping a few wells available for the required ETGA controls), and allowed to incubate for four to six hours.

It was proved that ligand exchange with a short acid molecule is

It was proved that ligand exchange with a short acid molecule is beneficial to a better electric contact between nanocrystals in inorganic QD solar cells [13, 14]. In this work, the nanomorphology

of the hybrid is critical to the performance of solar cells. A dense contact interface and good interpenetration of the two phases will be expectably beneficial to the performance of inorganic hybrid solar cells. Thus, a comparison of hybrid films with and without MPA this website treatment was given through SEM characterization in Figure  1c. Densely packed nanocrystal films with homogenous and pinhole-free surface over large areas were observed in both samples. Although there are a few cracks appearing after MPA treatment which is caused by the replacement of a long OA molecule chain, nanocrystal

aggregation composed of NTs and QDs is more clearly observed (Figure  1c(right)). The variation in surface morphology after surfactant exchange was also confirmed by AFM characterization in Figure  2. Figure 2 AFM height images of hybrid films with OA-capped hybrids (a) and after MPA treatment (b). The bottom images show the corresponding film surface height along the lines in the AFM images. As can be seen, the OA-capped hybrid nanoparticle thin films exhibit a homogeneous topology, while clusters and agglomerates can be found on the selleck screening library hybrid film after MPA treatment. The surface height along the Sinomenine line part of the AFM image was shown at the corresponding bottom. Mainly, tiny and uniform nanoclusters are observed on the OA-capped hybrid surface, while larger sized nanostructures are demonstrated after

MPA treatment, which means that aggregation of nanoparticles appears due to the removal of the long OA surfactant. Thus, ligand exchange correspondingly promotes a closer contact between the two phases from which charge transfer and transportation is benefited. In order to more clearly observe the hybrid morphology, TEM thin film samples were prepared by spin coating a SB203580 diluted hybrid solution onto a fixed copper net. The characterization results are shown in Figure  3. Without MPA treatment (Figure  3a,b,c), the hybrid presents a homogenous connection among NTs and QDs although there are some accumulations due to a large solution concentration (Figure  3a). Self-assembly of nanocrystals can be observed, showing uniform gaps between the adjacent particles (Figure  3b). Especially, the small CdSe quantum dots are presently surrounding and filling the gap of branched CdTe tetrapods (Figure  3c). The obvious self-assembling is caused by the existence of surfactants such as OA or TOPO. In contrast, agglomeration and aggregation in a large scale are shown after the hybrid film was solvent-treated with MPA (Figure  3d). The nanoparticles are densely connected and packed, which makes it difficult to tell where the CdSe quantum dots are located (Figure  3e,f).

Ethical approval for the feeding study was granted

by Car

Ethical approval for the feeding study was granted

by Cardiff School of Biosciences, Cardiff University (Approval number 079-1). Cultivation of LAB from faecal samples Fresh faecal samples were weighed, diluted 1:10 MRD diluent (Oxoid, Basingstoke, UK) containing 15% glycerol, and frozen at -80°C; no significant loss of cultivable diversity or viability was observed when freshly resuspended and plated faecal samples were compared to replicate samples that had been stored frozen. Serial dilutions were plated in replicate onto MRS and MRS-P agar, incubated at 37°C for 72 hours, and enumerated quantitatively and qualitatively prior to random picking of up to 10 the different colony morphotypes for RAPD fingerprinting. Each serial dilution plate was documented PD173074 chemical structure using digital photography; if RAPD detected the presence of either feeding study Alvocidib nmr strain (L. salivarius strain NCIMB 30211 RG7112 molecular weight or L. acidophilus strain NCIMB 30156; see Fig. 6), then retrospective counting of all the morphotypes associated with the strains was performed to determine a total count per gram of faeces. Statistical analysis For enumeration of the faecal counts on MRS-P agar, the mean and standard error of the

mean were determined and a 2-sample t-test to compare means (all numerical analysis was performed using MINITAB®

Release 15, Minitab Inc.). The overall results of the Lactobacillus feeding study were analysed non-parametrically using Chi square because of the limited number of subjects and the variables measured. A 2 × 2 data table was constructed for the analysis categorising the data as follows: two columns for the number of volunteers positive and negative for the administered Lactobacillus strains, respectively, and two rows for before and after capsule consumption, respectively (positive cultures selleck chemicals llc for any given volunteer were only counted once). Acknowledgements This work was supported by a grant from the HELP Wales Programme and Cultech Ltd. P.D. acknowledges salary funding from the Wellcome Trust (grant 075586). We thank: Catrin Thomas and Mark Weaver for technical assistance; Martin Day, Peter Vandamme, Julian Marchesi and Nigel Plummer for helpful discussions concerning the manuscript; and Peter Randerson for advice on the statistical analysis. References 1. Reid G: Probiotics and prebiotics – Progress and challenges. International Dairy Journal 2008,18(10–11):969–975.CrossRef 2.

To verify the effects of mycobacterial infection on the IL-10-ind

To verify the effects of mycobacterial infection on the IL-10-induced M2 polarization, the cell cultures were treated with recombinant IL-10. This treatment

induced in the BMDM expression of Arg-1 (Figure 4E) and secretion of IL-10 (Figure 4F) and MCP-1 (Figure selleck products 4B). Infection of these cells with the mycobacterial strains promoted expression of M2 markers, further increasing expression of the Arg-1 and suppressing inhibition of the MR expression induced by the H37Rv and B2 strains (Figure 4E). The infected cultures continued to secrete low levels of IL-10, induced by the exogenic IL-10 preselleck chemicals llc treatment (Figure 4F). Additionally, the treatment of MΦ with IL-10 suppressed ability of some mycobacterial strains to induce increased levels of secretion of proinflammatory mediators. Significant reduction of secretion of IL-6 and MCP-1 by MΦ infected with the H37Rv CA-4948 strain and MIP-2 chemokine secretion, induced by the strains B2 and MP287/03, was observed (Figure 4B). These data show that the proinflammatory activities of MΦ induced by mycobacterial infection were significantly inhibited in

the cells that were infected after priming by IL-10. These cells expressed MR and increased levels of Arg-1, which were particularly high in the cells infected with MP287/03 strain. Thus, the treatment with IL-10 favored M2-type activation of the infected MΦ. Discussion In this study, we aimed to investigate the modulating effects of pathogenic Mbv strains, differing in virulence-associated properties, on activation phenotypes in MΦ treated with the main cytokines regulating proinflammatory MΦ activation: IFN-γ

and IL-10. Rapid growth of pathogenic mycobacteria in MΦ is one of the known factors contributing to bacterial virulence [18, 19]. Therefore, for this work, we selected Carnitine palmitoyltransferase II two Mbv isolates differing significantly in the capacity to grow in MΦ. One of these isolates, strain B2, was capable of growing in BMDM at a rate similar to that of moderately virulent Mtb strain H37Rv, whereas the intracellular multiplication of other Mbv strain (MP287/03) was significantly faster. Additionally, we demonstrated that bacteria of MP287/03 strain continued to grow rapidly in cells activated by IFN-γ, whereas the growth of the strains B2 and H37Rv was significantly inhibited under this treatment. These data suggested that the MP287/03 strain was either more resistant to the bactericidal effects of macrophages classically activated by IFN-γ, or were able to inhibit MΦ activation induced by this cytokine. The modulating effects of the Mbv strains were evaluated in comparison to those of the reference Mtb strain H37Rv, which was demonstrated in previous studies to induce in MΦ a proinflammatory activation and synergize with IFN-γ in induction of M1-type polarization of infected cells [7, 20].