Genomic characterisation of Leptospira inadai serogroup Lyme isolated from captured rat in Brazil and comparative analysis with human reference strain.

Leptospira inadai is classified as a species of the Leptospira intermediate group that has been poorly studied due to its apparent insignificance to human and animal health. Nevertheless, over the last two decades the species has been described in human cases in India and in carrier animals in Ecuador. Here, we present the first identification and genomic characterisation of L. inadai serogroup Lyme isolated from captured rodent in Brazil. Even though the M34/99 strain was not pathogenic for hamsters, it was able to establish renal colonisation. The M34/99 strain presented high similarity with L. inadai serogroup Lyme human reference indicating that animal strain could also infect humans, although it does not represent high risk of severe disease. An extrachromosomal sequence was also identified in M34/99 strain and presented high identity with previously described L. inadai phage LinZ_10, suggesting that phage-like extrachromosomal sequence may be another feature of this understudied species.

Comparative genomic analysis of Brazilian Leptospira kirschneri serogroup Pomona serovar Mozdok.

Leptospira kirschneri is one of the pathogenic species of the Leptospira genus. Human and animal infection from L. kirschneri gained further attention over the last few decades. Here we present the isolation and characterisation of Brazilian L. kirschneri serogroup Pomona serovar Mozdok strain M36/05 and the comparative genomic analysis with Brazilian human strain 61H. The M36/05 strain caused pulmonary hemorrhagic lesions in the hamster model, showing high virulence. The studied genomes presented high symmetrical identity and the in silico multilocus sequence typing analysis resulted in a new allelic profile (ST101) that so far has only been associated with the Brazilian L. kirschneri serogroup Pomona serovar Mozdok strains. Considering the environmental conditions and high genomic similarity observed between strains, we suggest the existence of a Brazilian L. kirschneri serogroup Pomona serovar Mozdok lineage that could represent a high public health risk; further studies are necessary to confirm the lineage significance and distribution.

Genital bovine leptospirosis: A new look for an old disease.

Bovine leptospirosis is often associated with host-adapted leptospires infections, such as strains belonging to the Sejroe serogroup. Although bovine leptospirosis by adapted strains may result in abortions, fetal death, premature births and the birth of weak and/or low-weight calves, this infection is more closely associated with subtler syndromes, such as subfertility and early embryonic death. In this way, this silent disease can go unnoticed and undiagnosed, compromising reproductive efficiency with a consequent decrease in the productivity of herds over long periods. For many years, genital tract infection has been considered a secondary effect of renal infection with the assumption being that leptospires are found in the genital tract due to bacteremia caused by renal colonization. In contrast to this hypothesis, there is some evidence in the literature that suggests that genital leptospirosis should be considered a specific syndrome dissociated from renal/systemic disease. Therefore, this paper aims to gather and critically analyze information about genital leptospirosis in cattle, considering the disease a distinct syndrome, herein denominated bovine genital leptospirosis (BGL), that requires a unique approach to diagnosis and treatment.

Molecular epidemiology of Leptospira noguchii reveals important insights into a One Health context.

Leptospirosis presents a complex and dynamic epidemiology. Bovine leptospirosis has been described as a major infectious disease impairing reproductive efficiency. Although infections by Leptospira interrogans, L. santarosai and L. borgpetersenii are frequently reported in cattle, the presence of L. noguchii in these animals should not be neglected. In this study, we describe serological (MAT) and molecular characterization (rrs and secY gene sequencing, multilocus sequence typing [MLST] and pulsed-field gel electrophoresis [PFGE]) of eight L. noguchii strains obtained from slaughtered cows. Intraspecific genetic diversity was evaluated, and haplotype networks were constructed based on hosts and geographical localizations. Strains were characterized as belonging to serogroups Australis, Autumnalis and Panama, and molecular characterization showed a high heterogeneity of these strains. Ten different STs were found (including nine new STs and 39 novel alleles) as well as nine different pulsotypes. Two clonal complexes were found. Phylogenetic trees based on secY locus and concatenated MLST loci showed two main clusters, with sequences from the present study included in the first. In general, there was no relationship between the geographical origin and the secY phylogenetic clusters, as well as between secY phylogenetic clusters and serogroups. Molecular diversity indexes confirmed a high variability (H > 0.8). This high intraspecific variation observed may be related to differences in virulence, pathogenicity and antigenicity or even adaptability of the strains. In addition, haplotype networks clearly demonstrated the circulation of genotypes between humans and animals, confirming the zoonotic potential. The present study provides relevant data for the study of leptospirosis in the One Health context, where human, animal and environmental health is closely connected.

The redox balance of healthy Brazilian adults is associated with GPX1 Pro198Leu and -602A/G polymorphisms, selenium status, and anthropometric and lifestyle parameters.

PURPOSE: Considering that oxidative stress is implicated in the pathogenesis and progression of different health conditions, we aimed to evaluate whether the redox balance of a healthy Brazilian population is associated with GPX1 polymorphisms, selenium status, lipid profile, and anthropometric and lifestyle parameters. METHODS: 343 healthy adults were assessed for redox balance markers [glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity; malondialdehyde (MDA) and oxygen radical absorption capacity (ORAC)]; genotyped for the polymorphisms GPX1 Pro198Leu (rs1050450), -602A/G (rs3811699) and Arg5Pro (rs8179169); evaluated for selenium biomarkers (plasma, erythrocyte, and urine) and intake; and assessed for lipid profile. Anthropometric (BMI) and lifestyle data (physical activity, current smoking habit and alcohol consumption) were collected. Multivariable regression models were applied to investigate the possible associations. RESULTS: Although there were no differences in GPx activity according to GPX1 Pro198Leu and -602A/G polymorphisms, this redox balance marker was positively associated with erythrocyte selenium and negatively associated with the presence of a minor allele of Pro198Leu. SOD activity was positively associated with the presence of a minor allele for these polymorphisms. ORAC showed the same pattern among Leu and G carriers and was positively associated with Leu allele presence, BMI and alcohol intake. MDA was only associated negatively with the male sex and plasma selenium. CONCLUSIONS: Our findings suggest that the redox balance of a Brazilian healthy population is associated with GPX1 polymorphisms (Pro198Leu and -602A/G), selenium status, BMI, sex, smoking habit and alcohol consumption.

Genomic characterization and comparative analysis of Leptospira interrogans serogroup Australis isolated from swine.

The Leptospira interrogans serogroup Australis is traditionally described as pathogenic for swine although animals usually present low serologic response and mild clinical signs. The first isolation of a Leptospira interrogans serogroup Australis strain from swine, in Brazil, was recently described. Herein we present the genomic characterization of this strain (SU5) and further comparison with the Leptospira serovars reference genomes available in the GenBank database. The SU5 strain was characterized with sequence types previously described in a serogroup Australis isolated from human and presented a new ST98 that is thus far exclusively of the Brazilian porcine L. interrogans serogroup Australis. Even though the SU5 strain presented higher similarity with the American porcine serogroup Australis strain PigK151, as expected, it also presented sequences blocks in both chromosomes which are absent in the genomes of the studied Leptospira serovars. These regions are flanked by insertion sequences and transposases genes, suggesting the existence of inter- and intra-serogroup genomic variability due to mobile elements transferring. This genomic plasticity has already been demonstrated for pathogenic Leptospira species; nevertheless, there is still a limited understanding of the relationship between genome organization and content and the divergence of Leptospira serogroups and serovars that needs to be further elucidated.

Usage of Leptospira spp. local strains as antigens increases the sensitivity of the serodiagnosis of bovine leptospirosis.

Leptospirosis is a zoonotic disease that occurs worldwide, particularly in tropical countries. In livestock the agent is responsible for reproductive problems such as infertility and abortion. Serogroup Sejroe, particularly serovar Hardjo, prevails in cattle in several regions. The microscopic agglutination test (MAT) is the current method for diagnosing leptospirosis. It has been proposed that the inclusion of local strains could detect a larger set of seroreactive animals. In that context, the aim of the present study was to evaluate if the usage of local strains as antigens increases the sensitivity of the serodiagnosis of bovine leptospirosis. Blood and urine samples were collected from 314 bovines from several herds randomly selected in a slaughterhouse in Rio de Janeiro, Brazil. Serological diagnosis was made with MAT using a 21 reference-strains panel (MAT21). Additionally, 12 local strains (MAT33) were included as antigens. PCR was performed with the urine samples and it was positive on 71 out of 222 samples (31.9%). MAT21 identified as seroreactive 173 (55.1%) out of the 314 animals studied, with Sejroe the most common (38.1%). In MAT33, 204 (65.0%) animals were seroreactive with a significant increase on seroreactivity (9.9%). In conclusion, MAT presented with a significant increase of sensitivity when local strains were used as antigens. Among the local strains, 2013_U152 (KP263062) (serogroup Shermani) and 2013_U280 (KP263069) (serogroup Grippotyphosa) showed to be more antigenic.

Draft Genome Sequence of Brazilian Leptospira noguchii Serogroup Panama Strain U73, Isolated from Cattle.

Leptospira noguchii is a current zoonotic pathogen in Brazil. Here, we report the draft genome sequence of the Brazilian L. noguchii serogroup Panama strain U73, isolated from asymptomatic cattle urine.

Genomic characterisation of Leptospira inadai serogroup Lyme isolated from captured rat in Brazil and comparative analysis with human reference strain

Leptospira inadai is classified as a species of the Leptospira intermediate group that has been poorly studied due to its apparent insignificance to human and animal health. Nevertheless, over the last two decades the species has been described in human cases in India and in carrier animals in Ecuador. Here, we present the first identification and genomic characterisation of L. inadai serogroup Lyme isolated from captured rodent in Brazil. Even though the M34/99 strain was not pathogenic for hamsters, it was able to establish renal colonisation. The M34/99 strain presented high similarity with L. inadai serogroup Lyme human reference indicating that animal strain could also infect humans, although it does not represent high risk of severe disease. An extrachromosomal sequence was also identified in M34/99 strain and presented high identity with previously described L. inadai phage LinZ_10, suggesting that phage-like extrachromosomal sequence may be another feature of this understudied species.

Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death.

Induction of apoptotic cell death in response to chemotherapy and other external stimuli has proved extremely difficult in melanoma, leading to tumor progression, metastasis formation and resistance to therapy. A promising approach for cancer chemotherapy is the inhibition of proteasomal activity, as the half-life of the majority of cellular proteins is under proteasomal control and inhibitors have been shown to induce cell death programs in a wide variety of tumor cell types. 4-Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was able to induce the accumulation of ubiquitinated proteins, including classic targets of this process such as Mcl-1. As shown for other proteasomal inhibitors in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro-apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an artificial skin model containing melanoma also provided evidence that 4-NC prevented melanoma proliferation in a 3D model that more closely resembles normal human skin.

Comparative genomic analysis of Brazilian Leptospira kirschneri serogroup Pomona serovar Mozdok

Leptospira kirschneri is one of the pathogenic species of the Leptospira genus. Human and animal infection from L. kirschneri gained further attention over the last few decades. Here we present the isolation and characterisation of Brazilian L. kirschneri serogroup Pomona serovar Mozdok strain M36/05 and the comparative genomic analysis with Brazilian human strain 61H. The M36/05 strain caused pulmonary hemorrhagic lesions in the hamster model, showing high virulence. The studied genomes presented high symmetrical identity and the in silico multilocus sequence typing analysis resulted in a new allelic profile (ST101) that so far has only been associated with the Brazilian L. kirschneri serogroup Pomona serovar Mozdok strains. Considering the environmental conditions and high genomic similarity observed between strains, we suggest the existence of a Brazilian L. kirschneri serogroup Pomona serovar Mozdok lineage that could represent a high public health risk; further studies are necessary to confirm the lineage significance and distribution.

Lesoes em DNA produzidas por produtos secundarios da peroxidacao lipidica / DNA damage induced by secondary lipid oxidation products

A lipoperoxidacao tem sido associada a diversos mecanismos celulares deleterios que podem acarretar cancer, inflamacao e envelhecimento. Diversas evidencias indicam que os aldeidos, produzidos durante este processo sao mais toxicos do que os monohidroperoxidos dos quais sao originados. Aqui apresentamos um sumario dos principais resultados obtidos com relacao a danos em DNA produzidos por aldeidos reativos. Apesar dos mecanismos de envelhecimento e formacao de tumores ainda serem obscuros, a literatura recente indica a participacao de produtos secundarios da lipoperoxidacao na lesao cromossomal associada a estes processos