We investigated mutations in the genesIsoniazid (INH), a first-line antituberculosis drug, is bactericidal and has a simple chemical structure consisting of a pyridine ring and a hydrazide group. INH is a prodrug that enters actively growing tubercle bacilli by passive diffusion (2). The bifunctional bacterial enzyme catalase-peroxidase (KatG) converts INH to a range of oxygenated and organic toxic radicals that attack multiple targets in the mycobacterial cell (35,36,48). The best-characterized target of these radicals is the cell wall mycolic acid, but DNA, carbohydrates, lipids, and NAD metabolism may be targeted as well (16,36,50).The tuberculosis case rate in Brazil is the 15th highest in the world, with an estimated prevalence of 64 cases per 100,000 population; moreover, ϳ0.9% of the new cases are multidrug resistant (45). A recent nationwide investigation of primary INH resistance found a national frequency of 3.8% (29); however, the percentages varied greatly between geographic regions of the country.

Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC-MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. The composition of the essential oil of Piper mosenii was described for the first time. The cytotoxicity of the essential oils was evaluated in peritoneal macrophages and the oils of P. rivinoides, P. arboretum, and P. aduncum exhibited the highest values, with cytotoxic concentration at 50% (CC 50 ) > 200 µg/mL. Both P. diospyrifolium and P. aduncum displayed activity against Leishmania amazonensis, and were more selective for the parasite than for the macrophages, with a selectivity index (SI) of 2.35 and >5.52, respectively. These SI values were greater than the 1 for the standard drug pentamidine. The antileishmanial activity of the essential oils of P. diospyrifolium and P. aduncum was described for the first time. P. rivinoides, P. cernuum, and P. diospyrifolium displayed moderate activity against the Mycobacterium tuberculosis H 37 Rv bacillus, with a minimum inhibitory concentration (MIC) of 125 µg/mL. These results are relevant and suggests their potential for therapeutic purposes. Nevertheless, further studies are required to explain the exact mechanism of action of these essential oils.

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These results contribute to the knowledge of the molecular mechanism of pyrazinamide resistance in Brazil and also expand the profile of pncA mutations worldwide. The MABA was successfully used to determine the MICs of pyrazinamide.

In developing nations, 10-20% of the human cases of tuberculosis are caused by Mycobacterium bovis. However, this percentage may be underestimated because most laboratories in developing countries do not routinely perform mycobacterial cultures, and only a few have the systems in place to identify M. bovis. There are few studies investigating genotypic diversity and drug resistance in M. bovis from animal and/or human infections. The genotypic diversity of M. bovis strains obtained from bovine lymph nodes were investigated by spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive unit-variable-number tandem repeat typing (MIRU-VNTR). The phenotypic resistance to isoniazid and rifampicin and MIC values of the isolates were determined using the resazurin microtiter assay plate method (REMA). The evaluation of the possible genetic basis for such resistance was performed with GenoType MTBDRplus. Sixty-seven isolates were obtained, of which 11 (16%) were MDR-TB, 8 (12%) were isoniazid-resistant, and 2 (3%) were rifampicin-resistant. Mutations associated with drug resistance were not found. Genotyping techniques enabled the grouping of the strains into 12 clusters and 21 isolates with unique profiles. The high frequency of M. bovis reinforces the impact of the pathogen as a major causal agent of bovine tuberculosis in the study area. The resistance of the strains to drugs used for first-line treatment of human tuberculosis raises public health concerns. Further studies are required to elucidate the basis of drug resistance and genotypic diversity in M. bovis.

Introduction The aim of this study was to determine the prevalence of GBS colonization in pregnant women in a public health service.Methods A study of 496 pregnant women at 35-37 gestational weeks was conducted from September 2011 to March 2014 in 21 municipalities of the 18th Health Region of Paraná State. Vaginal and anorectal samples of each woman were plated on sheep blood agar, and in HPTH and Todd-Hewitt enrichment broths.Results Of the 496 pregnant women, 141 (28.4%) were positive for GBS based on the combination of the three culture media with vaginal and anorectal samples. The prevalence was 23.7% for vaginal samples and 21.9% for anorectal ones. Among the variables analyzed in this study, only urinary infection was a significant factor (0.026) associated with GBS colonization in women.Conclusions Based on these results, health units should performs universal screening of pregnant women and hospitals should provide adequate prophylaxis, when indicated.

The aim of the present study was to (i) evaluate the in vitro action of rifampicin (RIF), ethambutol or isoniazid with efflux pumps inhibitors (EPIs) in Mycobacterium tuberculosis (Mtb) H37Rv and (ii) evaluate the morphological and efflux pumps (EPs) transcriptional changes by the action of rifampicin + verapamil combination (RIF + VP). The minimal inhibitory concentration and synergic effect of drug combinations were determined by Resazurin Microtiter Plate Assay and Resazurin Drugs Combination Microtiter Assay, respectively. VP showed greater capacity of ethidium bromide accumulation and RIF + VP had the lower fractional inhibitory concentration index. The RIF + VP exerted a similar reduction of viable cell counts to RIF by time-kill curve, but decreases in the expression of EPs genes were observed by Real time PCR at 72 h of RIF + VP exposure. Accumulative morphological changes (wrinkled and rounding) caused by each drug were observed by scanning electron microscopy after RIF + VP exposure. The downexpression of EPs related genes exposed to RIF + VP, suggest an effective inhibitory activity of VP in Mtb H37Rv. The role of EPs and the use of EPIs open up a powerful approach and the RIF + VP combination should be studied in Mtb more thoroughly.

SUMMARYIntroduction:Group B streptococcus (GBS) or Streptococcus agalactiae can colonize the gastrointestinal and genitourinary tracts and has been considered one of the most important risk factors for the development of neonatal disease. The present study evaluated the antimicrobial susceptibility of GBS isolates from pregnant women who were attended at a public health service in Northern Paraná, Brazil. Methods:A descriptive analytical cross-sectional study was performed with 544 pregnant women, at ≥ 35 weeks of gestation. One hundred and thirty-six GBS isolates from pregnant women were tested for antimicrobial susceptibility. Results:All of the GBS isolates showed susceptibility to the drug that is most frequently used for intrapartum prophylaxis: penicillin. Resistance to clindamycin and erythromycin was detected, thus decreasing the options of prophylaxis in women who are allergic to penicillin. Conclusions: Additional studies should be conducted to increase the knowledge of GBS sensitivity profile to antimicrobials in other health centers.