DeepHost: phage host prediction with convolutional neural network.

Next-generation sequencing expands the known phage genomes rapidly. Unlike culture-based methods, the hosts of phages discovered from next-generation sequencing data remain uncharacterized. The high diversity of the phage genomes makes the host assignment task challenging. To solve the issue, we proposed a phage host prediction tool-DeepHost. To encode the phage genomes into matrices, we design a genome encoding method that applied various spaced $k$-mer pairs to tolerate sequence variations, including insertion, deletions, and mutations. DeepHost applies a convolutional neural network to predict host taxonomies. DeepHost achieves the prediction accuracy of 96.05% at the genus level (72 taxonomies) and 90.78% at the species level (118 taxonomies), which outperforms the existing phage host prediction tools by 10.16-30.48% and achieves comparable results to BLAST. For the genomes without hits in BLAST, DeepHost obtains the accuracy of 38.00% at the genus level and 26.47% at the species level, making it suitable for genomes of less homologous sequences with the existing datasets. DeepHost is alignment-free, and it is faster than BLAST, especially for large datasets. DeepHost is available at https://github.com/deepomicslab/DeepHost.

Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia.

Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of Staphylococcus aureus. We previously identified a monoclonal antibody (MAb) against AT that reduced disease severity in a mouse dermonecrosis model. Here, we evaluate the activity of an affinity-optimized variant, LC10, in a mouse model of S. aureus pneumonia. Passive immunization with LC10 increased survival and reduced bacterial numbers in the lungs and kidneys of infected mice and showed protection against diverse S. aureus clinical isolates. The lungs of S. aureus-infected mice exhibited bacterial pneumonia, including widespread inflammation, whereas the lungs of mice that received LC10 exhibited minimal inflammation and retained healthy architecture. Consistent with reduced immune cell infiltration, LC10-treated animals had significantly lower (P < 0.05) proinflammatory cytokine and chemokine levels in the bronchoalveolar lavage fluid than did those of the control animals. This reduction in inflammation and damage to the LC10-treated animals resulted in reduced vascular protein leakage and CO2 levels in the blood. LC10 was also assessed for its therapeutic activity in combination with vancomycin or linezolid. Treatment with a combination of LC10 and vancomycin or linezolid resulted in a significant increase (P < 0.05) in survival relative to the monotherapies and was deemed additive to synergistic by isobologram analysis. Consistent with improved survival, the lungs of animals treated with antibiotic plus LC10 exhibited less inflammatory tissue damage than those that received monotherapy. These data provide insight into the mechanisms of protection provided by AT inhibition and support AT as a promising target for immunoprophylaxis or adjunctive therapy against S. aureus pneumonia.

Progression to insulin for patients with diabetes mellitus on dual oral antidiabetic therapy using the US Department of Defense Database.

AIM: To compare 'progression to insulin' for three cohorts on oral antidiabetic medication combinations: metformin/sulphonylurea (Met/SU), metformin/thiazolidinedione (Met/TZD) and sulphonylurea/thiazolidinedione (SU/TZD). METHODS: Retrospective cohort analysis design was used. The subjects were US nationwide members of military and their families. A total of 5608 patients who were on antidiabetic monotherapy for at least 1 year before adding a second agent to their medication regimen between October 2001 and September 2008 participated in this study. Mean age ranged from 64 to 71 years among the cohorts. Cox regression compared the progression to insulin, adjusting for demographics, months of follow-up and co-morbidities [measured with Chronic Disease Score (CDS)]. RESULTS: By the end of the 2- to 6-year follow-up period, 14.3% of the Met/TZD cohort, 23.6% of the Met/SU cohort and 28.2% of the SU/TZD cohort had insulin added to their regimen. Those in the Met/SU cohort had a 1.8 times higher probability of progression to insulin than those in the Met/TZD cohort [odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.51-2.14), and those in the SU/TZD cohort had a 2.5 times higher probability of progression to insulin than those in the Met/TZD cohort (OR = 2.51, 95% CI = 2.04-3.08). CONCLUSION: When sensitizers were paired (Met/TZD), a lower percentage of patients progressed to insulin during the study period, as opposed to patients who used a combination of a secretagogue with a sensitizer (SU/TZD or Met/SU).

Mycobacterium tuberculosis in zoo and wildlife species.

Tuberculosis caused by Mycobacterium tuberculosis and M. tuberculosis-like organisms has been identified in a wide range of species, including non-human primates, elephants and other exotic ungulates, carnivores, marine mammals and psittacine birds. Disease associated with M. tuberculosis has occurred mostly within captive settings and does not appear to occur naturally in free-living mammals. Mycobacterium tuberculosis probably originated as an infection of humans, but from the zoonotic standpoint, non-human primates, Asian elephants and psittacine birds have the potential to transmit this disease to humans. However, the overall prevalence of disease in these susceptible species is low and documented transmissions of M. tuberculosis between animals and humans are uncommon. Mycobacterium tuberculosis causes progressive pulmonary disease in mammals and a muco-cutaneous disease in parrots. In all cases, the disease can disseminate and be shed into the environment. Diagnosis in living animals is based on intradermal tuberculin testing in non-human primates, culturing trunk secretions in elephants, and biopsy and culture of external lesions in parrots. Ancillary testing with deoxyribonucleic acid probes and nucleic acid amplification, and enzyme-linked immunosorbent assays have been adapted to some of these species with promising results. Additionally, new guidelines for controlling tuberculosis in elephants in the United States of America, and programmes for tuberculosis prevention in animal handlers have been established.