The fall and rise of group B Streptococcus in dairy cattle: reintroduction due to human-to-cattle host jumps?
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ABSTRACT:
SUBMITTER: Crestani C
PROVIDER: S-EPMC8715428 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Group B Streptococcus (GBS), is a leading cause of neonatal death and an emerging pathogen in adults. Additionally, GBS is a bovine pathogen causing intramammary infections. The likelihood of GBS interspecies transmission is largely unknown. We explored the potential transmission of GBS between cattle and people on dairy farms in Colombia and compared the antimicrobial resistance (AMR) profiles of isolates from both host species. Across 33 farms, throat swabs and rectal swabs were collected from 191 people, and rectal swabs and composite milk samples from 2092 cattle, yielding 60 human isolates and 301 bovine isolates. The majority (64%) of isolates belonged to shared sequence types (ST). Sequence type (ST) 1 was the most common strain in both host species, suggesting that interspecies transmission may be possible. Two members of the bovine-specific clonal complex 61/67 were detected in human samples (ST718 and ST1175), providing evidence for the lack of genuine species barriers. Apparent prevalence of penicillin resistance was surprisingly high in human and bovine isolates. Further investigation of this phenomenon is needed and could lead to modification of standard testing and treatment recommendations in human and veterinary medicine.
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Project description:Dimebon (latrepirdine) was developed and used in Russia as an over-the-counter oral antihistamine for allergy treatment. In the early 1990s, Dimebon was characterized as a low-affinity NMDA receptor antagonist by Dr. Sergey Bachurin and his colleagues. An initial small-scale, open-label trial of Dimebon in 14 Alzheimer's disease (AD) patients demonstrated potential efficacy. Dimebon was then patented for the treatment of neurodegenerative disorders and licensed by Medivation. Extremely promising results were obtained in a double-blind, placebo-controlled, phase II AD trial in 183 patients; however, a phase II trial of Dimebon in 91 Huntington's disease patients was much less successful. Recently, a phase III AD trial of Dimebon in 598 patients failed to result in any significant improvement in primary or secondary outcomes. The failure of Dimebon may be in large part due to insufficient understanding of its mechanism of action. The NMDA receptor blocking activity of Dimebon is too weak to be physiologically relevant, while the proposed "novel mitochondrial mechanism of action" lacks credible scientific evidence or a molecular target. Independent studies indicate that the clinical effects of Dimebon most likely result from inhibition of histamine H₁ and serotonin 5-HT₆ receptors. Careful preclinical studies of novel potential therapies are needed to minimize chances of making similar costly mistakes in the future.
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Project description:BACKGROUND:Inbreeding decreases animal performance (inbreeding depression), but not all inbreeding is expected to be equally harmful. Recent inbreeding is expected to be more harmful than ancient inbreeding, because selection decreases the frequency of deleterious alleles over time. Selection efficiency is increased by inbreeding, a process called purging. Our objective was to investigate effects of recent and ancient inbreeding on yield, fertility and udder health traits in Dutch Holstein-Friesian cows. METHODS:In total, 38,792 first-parity cows were included. Pedigree inbreeding ([Formula: see text]) was computed and 75 k genotype data were used to compute genomic inbreeding, among others based on regions of homozygosity (ROH) in the genome ([Formula: see text]). RESULTS:Inbreeding depression was observed, e.g. a 1% increase in [Formula: see text] was associated with a 36.3 kg (SE?=?2.4) decrease in 305-day milk yield, a 0.48 day (SE?=?0.15) increase in calving interval and a 0.86 unit (SE?=?0.28) increase in somatic cell score for day 150 through to 400. These effects equalled -?0.45, 0.12 and 0.05% of the trait means, respectively. When [Formula: see text] was split into generation-based components, inbreeding on recent generations was more harmful than inbreeding on more distant generations for yield traits. When [Formula: see text] was split into new and ancestral components, based on whether alleles were identical-by-descent for the first time or not, new inbreeding was more harmful than ancestral inbreeding, especially for yield traits. For example, a 1% increase in new inbreeding was associated with a 2.42 kg (SE?=?0.41) decrease in 305-day fat yield, compared to a 0.03 kg (SE?=?0.71) increase for ancestral inbreeding. There were no clear differences between effects of long ROH (recent inbreeding) and short ROH (ancient inbreeding). CONCLUSIONS:Inbreeding depression was observed for yield, fertility and udder health traits. For yield traits and based on pedigree, inbreeding on recent generations was more harmful than inbreeding on distant generations and there was evidence of purging. Across all traits, long and short ROH contributed to inbreeding depression. In future work, inbreeding depression and purging should be assessed in more detail at the genomic level, using higher density information and genomic time series.
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Project description:In response to tissue injury, hyaluronan (HA) polymers are cleaved by host hyaluronidases, generating small fragments that ligate Toll-like receptors (TLRs) to elicit inflammatory responses. Pathogenic bacteria such as group B Streptococcus (GBS) express and secrete hyaluronidases as a mechanism for tissue invasion, but it is not known how this activity relates to immune detection of HA. We found that bacterial hyaluronidases secreted by GBS and other Gram-positive pathogens degrade pro-inflammatory HA fragments to their component disaccharides. In addition, HA disaccharides block TLR2/4 signaling elicited by both host-derived HA fragments and other TLR2/4 ligands, including lipopolysaccharide. Application of GBS hyaluronidase or HA disaccharides reduced pulmonary pathology and pro-inflammatory cytokine levels in an acute lung injury model. We conclude that breakdown of host-generated pro-inflammatory HA fragments to disaccharides allows bacterial pathogens to evade immune detection and could be exploited as a strategy to treat inflammatory diseases.
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Project description:The surge of post-truth political argumentation suggests that we are living in a special historical period when it comes to the balance between emotion and reasoning. To explore if this is indeed the case, we analyze language in millions of books covering the period from 1850 to 2019 represented in Google nGram data. We show that the use of words associated with rationality, such as "determine" and "conclusion," rose systematically after 1850, while words related to human experience such as "feel" and "believe" declined. This pattern reversed over the past decades, paralleled by a shift from a collectivistic to an individualistic focus as reflected, among other things, by the ratio of singular to plural pronouns such as "I"/"we" and "he"/"they." Interpreting this synchronous sea change in book language remains challenging. However, as we show, the nature of this reversal occurs in fiction as well as nonfiction. Moreover, the pattern of change in the ratio between sentiment and rationality flag words since 1850 also occurs in New York Times articles, suggesting that it is not an artifact of the book corpora we analyzed. Finally, we show that word trends in books parallel trends in corresponding Google search terms, supporting the idea that changes in book language do in part reflect changes in interest. All in all, our results suggest that over the past decades, there has been a marked shift in public interest from the collective to the individual, and from rationality toward emotion.
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Project description:Science advances by pushing the boundaries of the adjacent possible. While the global scientific enterprise grows at an exponential pace, at the mesoscopic level the exploration and exploitation of research ideas are reflected through the rise and fall of research fields. The empirical literature has largely studied such dynamics on a case-by-case basis, with a focus on explaining how and why communities of knowledge production evolve. Although fields rise and fall on different temporal and population scales, they are generally argued to pass through a common set of evolutionary stages. To understand the social processes that drive these stages beyond case studies, we need a way to quantify and compare different fields on the same terms. In this paper we develop techniques for identifying common patterns in the evolution of scientific fields and demonstrate their usefulness using 1.5 million preprints from the arXiv repository covering 175 research fields spanning Physics, Mathematics, Computer Science, Quantitative Biology and Quantitative Finance. We show that fields consistently follow a rise and fall pattern captured by a two parameters right-tailed Gumbel temporal distribution. We introduce a field-specific re-scaled time and explore the generic properties shared by articles and authors at the creation, adoption, peak, and decay evolutionary phases. We find that the early phase of a field is characterized by disruptive works mixing of cognitively distant fields written by small teams of interdisciplinary authors, while late phases exhibit the role of specialized, large teams building on the previous works in the field. This method provides foundations to quantitatively explore the generic patterns underlying the evolution of research fields in science, with general implications in innovation studies.
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Project description:Streptococcus agalactiae is a pathogen-associated to bovine mastitis, a health disorder responsible for significant economic losses in the dairy industry. Antimicrobial therapy remains the main strategy for the control of this bacterium in dairy herds and human In order to get insight on molecular characteristics of S. agalactiae strains circulating among Argentinean cattle with mastitis, we received 1500 samples from 56 dairy farms between 2016 and 2019. We recovered 56 S. agalactiae isolates and characterized them in relation to serotypes, virulence genes, and antimicrobial susceptibility. Serotypes III and II were the most prevalent ones (46% and 41%, respectively), followed by Ia (7%). In relation to the 13 virulence genes screened in this study, the genes spb1, hylB, cylE, and PI-2b were present in all the isolates, meanwhile, bca, cpsA, and rib were detected in different frequencies, 36%, 96%, and 59%, respectively. On the other hand, bac, hvgA, lmb, PI-1, PI-2a, and scpB genes could not be detected in any of the isolates. Disk diffusion method against a panel of eight antimicrobial agents showed an important number of strains resistant simultaneously to five antibiotics. We also detected several resistance-encoding genes, tet(M), tet(O), ermB, aphA3, and lnu(B) (9%, 50%, 32%, 32%, and 5%, respectively). The results here presented are the first molecular data on S. agalactiae isolates causing bovine mastitis in Argentina and provide a foundation for the development of diagnostic, prophylactic, and therapeutic methods, including the perspective of a vaccine.
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