Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function

Background

The Nef protein of HIV facilitates virus replication and disease progression in infected patients. This role as pathogenesis factor depends on several genetically separable Nef functions that are mediated by interactions of highly conserved protein-protein interaction motifs with different host cell proteins. By studying the functionality of a series of nef alleles from clinical isolates, we identified a dysfunctional HIV group O Nef in which a highly conserved valine-glycine-phenylalanine (VGF) region, which links a preceding acidic cluster with the following proline-rich motif into an amphipathic surface was deleted. In this study, we aimed to study the functional importance of this VGF region.

Results

The dysfunctional HIV group O8 nef allele was restored to the consensus sequence, and mutants of canonical (NL4.3, NA-7, SF2) and non-canonical (B2 and C1422) HIV-1 group M nef alleles were generated in which the amino acids of the VGF region were changed into alanines (VGF??AAA) and tested for their capacity to interfere with surface receptor trafficking, signal transduction and enhancement of viral replication and infectivity. We found the VGF motif, and each individual amino acid of this motif, to be critical for downregulation of MHC-I and CXCR4. Moreover, Nef??s association with the cellular p21-activated kinase 2 (PAK2), the resulting deregulation of cofilin and inhibition of host cell actin remodeling, and targeting of Lck kinase to the trans-golgi-network (TGN) were affected as well. Of particular interest, VGF integrity was essential for Nef-mediated enhancement of HIV virion infectivity and HIV replication in peripheral blood lymphocytes. For targeting of Lck kinase to the TGN and viral infectivity, especially the phenylalanine of the triplet was essential. At the molecular level, the VGF motif was required for the physical interaction of the adjacent proline-rich motif with Hck.

Conclusion

Based on these findings, we propose that this highly conserved three amino acid VGF motif together with the acidic cluster and the proline-rich motif form a previously unrecognized amphipathic surface on Nef. This surface appears to be essential for the majority of Nef functions and thus represents a prime target for the pharmacological inhibition of Nef.     

Para‐psychobiotic Lactobacillus gasseri CP2305 ameliorates stress‐related symptoms and sleep quality

Aims

To confirm the stress‐relieving effects of heat‐inactivated, enteric‐colonizing Lactobacillus gasseri CP2305 (paraprobiotic CP2305) in medical students taking a cadaver dissection course.

Methods and Results

Healthy students (21 males and 11 females) took paraprobiotic CP2305 daily for 5 weeks during a cadaver dissection course. The General Health Questionnaire and the Pittsburgh Sleep Quality Index were employed to assess stress‐related somatic symptoms and sleep quality respectively. The aggravation of stress‐associated somatic symptoms was observed in female students (P = 0·029). Sleep quality was improved in the paraprobiotic CP2305 group (P = 0·038), particularly in men (P = 0·004). Among men, paraprobiotic CP2305 shortened sleep latency (P = 0·035) and increased sleep duration (P = 0·048). Diarrhoea‐like symptoms were also effectively controlled with CP2305 (P = 0·005) in men. Thus, we observed sex‐related differences in the effects of paraprobiotic CP2305. In addition, CP2305 affected the growth of faecal Bacteroides vulgatus and Dorea longicatena, which are involved in intestinal inflammation.

Conclusions

CP2305 is a potential paraprobiotic that regulates stress responses, and its beneficial effects may depend on specific cell component(s).

Significance and Impact of the Study

This study characterizes the effects of a stress‐relieving para‐psychobiotic in humans.     

Conservation prioritisation through genomic reconstruction of demographic histories applied to two endangered suids in the Malay Archipelago

Aim

The biodiversity of the Malay Archipelago is the product of the region's rich biogeographical history with periods of island connectivity and isolation during the Pleistocene glacial cycles. Here, the case of two endemic suid species, the Javan (Sus verrucosus) and Bawean (S. blouchi) warty pigs, was used to illustrate how biogeographic processes and recent anthropogenic pressures can shape demographic histories with significant implications for species conservation.

Location

Malay Archipelago, with focus on Bawean and Java.

Methods

We employed genome-wide single nucleotide polymorphisms from the Porcine SNP60 v2 BeadChip to assess interspecific genetic differentiation, to estimate divergence times and to perform demographic model selection.

Results

In contrast to the hypothesis of recent divergence during the last glacial maximum, S. blouchi was found to have diverged from S. verrucosus at least 166 k years ago following a founder event. The contemporary S. blouchi population was characterised by a recent bottleneck that reduced the effective population size to less than 20. The genomic assessment supports the single species status of S. blouchi, as was previously proposed based on morphometrics. The demographic history of S. verrucosus showed evidence of secondary contact with the sympatric banded pig (S. scrofa vittatus) that colonised Java 70 k years ago.

Main Conclusions

While the Javan and Bawean warty pigs have persisted throughout the Pleistocene climatic oscillations, contemporary pressures from human activities threaten their survival and immediate action should be taken to grant legal protection to both S. verrucosus and S. blouchi. This study highlighted the use of demographic history modelling using genomic data to identify evolutionary significant units and inform conservation.     

Human appropriation of net primary production as driver of change in landscape-scale vertebrate richness

Aim

Land use is the most pervasive driver of biodiversity loss. Predicting its impact on species richness (SR) is often based on indicators of habitat loss. However, the degradation of habitats, especially through land-use intensification, also affects species. Here, we evaluate whether an integrative metric of land-use intensity, the human appropriation of net primary production, is correlated with the decline of SR in used landscapes across the globe.

Location

Global.

Time period

Present.

Major taxa studied

Birds, mammals and amphibians.

Methods

Based on species range maps (spatial resolution: 20 km × 20 km) and an area-of-habitat approach, we calibrated a “species–energy model” by correlating the SR of three groups of vertebrates with net primary production and biogeographical covariables in “wilderness” areas (i.e., those where available energy is assumed to be still at pristine levels). We used this model to project the difference between pristine SR and the SR corresponding to the energy remaining in used landscapes (i.e., SR loss expected owing to human energy extraction outside wilderness areas). We validated the projected species loss by comparison with the realized and impending loss reconstructed from habitat conversion and documented by national Red Lists.

Results

Species–energy models largely explained landscape-scale variation of mapped SR in wilderness areas (adjusted R²-values: 0.79–0.93). Model-based projections of SR loss were lower, on average, than reconstructed and documented ones, but the spatial patterns were correlated significantly, with stronger correlation in mammals (Pearson's r = 0.68) than in amphibians (r = 0.60) and birds (r = 0.57).

Main conclusions

Our results suggest that the human appropriation of net primary production is a useful indicator of heterotrophic species loss in used landscapes, hence we recommend its inclusion in models based on species–area relationships to improve predictions of land-use-driven biodiversity loss.     

The identity and distribution of neural cells expressing the mesodermal determinant spadetail

Background  

The spadetail (spt) gene of zebrafish is expressed in presomitic mesoderm and in neural cells previously suggested to be Rohon-Beard neurons. The mechanism(s) generating the apparently irregular rostrocaudal distribution of spt-expressing cells in the developing CNS is unknown.     

Biochanin A improves fibre fermentation by cellulolytic bacteria

Aims

The objective was to determine the effect of the isoflavone biochanin A (BCA) on rumen cellulolytic bacteria and consequent fermentative activity.

Methods and Results

When bovine microbial rumen cell suspensions (n = 3) were incubated (24 h, 39°C) with ground hay, cellulolytic bacteria proliferated, short‐chain fatty acids were produced and pH declined. BCA (30 μg ml^?1) had no effect on the number of cellulolytic bacteria or pH, but increased acetate, propionate and total SCFA production. Addition of BCA improved total digestibility when cell suspensions (n = 3) were incubated (48 h, 39°C) with ground hay, Avicel, or filter paper. Fibrobacter succinogenes S85, Ruminococcus flavefaciens 8 and Ruminococcus albus 8 were directly inhibited by BCA. Synergistic antimicrobial activity was observed with BCA and heat killed cultures of cellulolytic bacteria, but the effects were species dependent.

Conclusions

These results indicate that BCA improves fibre degradation by influencing cellulolytic bacteria competition and guild composition.

Significance and Impact of the Study

BCA could serve as a feed additive to improve cellulosis when cattle are consuming high‐fibre diets. Future research is needed to evaluate the effect of BCA on fibre degradation and utilization in vivo.     

Clavibacter nebraskensis causing Goss's wilt of maize: Five decades of detaining the enemy in the New World

Goss's bacterial wilt and leaf blight of maize (Zea mays) caused by the gram-positive coryneform bacterium Clavibacter nebraskensis is an economically important disease in North America. C. nebraskensis is included within the high-risk list of quarantine pathogens by several plant protection organizations (EPPO code: CORBMI), hence it is under strict quarantine control around the world. The causal agent was reported for the first time on maize in Nebraska (USA) in 1969. After an outbreak during the 1970s, prevalence of the disease decreased in the 1980s to the early 2000s, before the disease resurged causing a serious threat to maize production in North America. The re-emergence of Goss's wilt in the corn belt of the United States led to several novel achievements in understanding the pathogen biology and disease control. In this review, we provide an updated overview of the pathogen taxonomy, biology, and epidemiology as well as management strategies of Goss's wilt disease. First, a taxonomic history of the pathogen is provided followed by symptomology and host range, genetic diversity, and pathogenicity mechanisms of the bacterium. Then, utility of high-throughput molecular approaches in the precise detection and identification of the pathogen and the management strategies of the disease are explained. Finally, we highlight the role of integrated pest management strategies to combat the risk of Goss's wilt in the 21st century maize industry.

Disease symptoms

Large (2–15 cm) tan to grey elongated oval lesions with wavy, irregular water-soaked margins on the leaves. The lesions often start at the leaf tip or are associated with wounding caused by hail or wind damage. Small (1 mm in diameter), dark, discontinuous water-soaked spots, known as “freckles”, can be observed in the periphery of lesions. When backlit, the freckles appear translucent. Early infection (prior to growth stage V6) may become systemic and cause seedlings to wilt, wither, and die. Coalescence of lesions results in leaf blighting.

Host range

Maize (Zea mays) is the only economic host of the pathogen. A number of Poaceae species are reported to act as secondary hosts for C. nebraskensis.

Taxonomic status of the pathogen

Class: Actinobacteria; Order: Micrococcales; Family: Microbacteriaceae; Genus: Clavibacter; Species: Clavibacter nebraskensis.

Synonyms

Corynebacterium nebraskense (Schuster, 1970) Vidaver & Mandel 1974; Corynebacterium michiganense pv. nebraskense (Vidaver & Mandel 1974) Dye & Kemp 1977; Corynebacterium michiganense subsp. nebraskense (Vidaver & Mandel 1974) Carlson & Vidaver 1982; Clavibacter michiganense subsp. nebraskense (Vidaver & Mandel 1974) Davis et al. 1984; Clavibacter michiganensis subsp. nebraskensis (Vidaver & Mandel 1974) Davis et al. 1984.

Type materials

ATCC 27794^T; CFBP 2405^T; ICMP 3298^T; LMG 3700^T; NCPPB 2581^T.

Microbiological properties

Cells are gram-positive, orange-pigmented, pleomorphic club- or rod-shaped, nonspore-forming, nonmotile, and without flagella, approximately 0.5 × 1–2.0 μm.

Distribution

The pathogen is restricted to Canada and the United States.

Phytosanitary categorization

EPPO code CORBNE.     

Identification of a gonadotropin-releasing hormone receptor orthologue in Caenorhabditis elegans

Background  

The Caenorhabditis elegans genome is known to code for at least 1149 G protein-coupled receptors (GPCRs), but the GPCR(s) critical to the regulation of reproduction in this nematode are not yet known. This study examined whether GPCRs orthologous to human gonadotropin-releasing hormone receptor (GnRHR) exist in C. elegans.     

Helicobacter pylori infection reduces the risk of Barrett's esophagus: A meta‐analysis and systematic review

Introduction

The prevalence of Helicobacter pylori infection (HPI) has been decreasing in developed countries, with an increasing prevalence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) at the same time. The aim of our meta‐analysis was to quantify the risk of BE in the context of HPI.

Methods

A systematic search was conducted in 3 databases for studies on BE with data on prevalence of HPI from inception until December 2016. Odds ratios for BE in HPI were calculated by the random effects model with subgroup analyses for geographical location, presence of dysplasia in BE, and length of the BE segment.

Results

Seventy‐two studies were included in the meta‐analysis, including 84 717 BE cases and 390 749 controls. The overall analysis showed that HPI reduces the risk of BE; OR = 0.68 (95% CI: 0.58‐0.79, P < .001). Subgroup analyses revealed risk reduction in Asia OR = 0.53 (95% CI: 0.33‐0.84, P = .007), Australia OR = 0.56 (95% CI: 0.39‐0.80, P = .002), Europe OR = 0.77 (95% CI: 0.60‐0.98, P = .035), and North‐America OR = 0.59 (95% CI: 0.47‐0.74, P < .001). The risk was significantly reduced for dysplastic BE, OR = 0.37 (95% CI: 0.26‐0.51, P < .001) for non‐dysplastic BE, OR = 0.51 (95% CI: 0.35‐0.75, P = .001), and for long segment BE, OR = 0.25 (95% CI: 0.11‐0.59, P = .001) in case of HPI.

Conclusions

This extensive meta‐analysis provides additional evidence that HPI is associated with reduced risk of BE. Subgroup analyses confirmed that this risk reduction is independent of geographical location. HPI is associated with significantly lower risk of dysplastic, non‐dysplastic, and long segment BE.     

Genetic diversity and colony structure of Tapinoma melanocephalum on the islands and mainland of South China

Aim

Tapinoma melanocephalum is listed as one of the most important invasive pest species in China. Information regarding the patterns of invasion and effects of geographic isolation on the population genetics of this species is largely lacking.

Location

South China.

Methods

To address this problem, we genotyped 39 colonies (two colonies were collapsed due to genetic similarity) using microsatellite markers and mitochondrial DNA sequencing to compare colony genetic structure of T. melanocephalum on the mainland and islands of South China.

Results

An analysis of the colony genotypes showed that the genetic diversity of the mainland population was slightly higher than that of the island populations but not significantly so. However, the observed heterozygosity on Shangchuan Island (SCD) was significantly lower than that of the other colonies. We also found six haplotypes in 111 mitochondrial DNA COI sequences. The relatedness (r) value between colonies of SCD was 0.410, higher than that of the other populations. The genetic clusters among colonies were not related to geographic locations and exhibited admixture likely due to frequent human‐mediated dispersal associated with trade between the mainland population and the islands. Pairwise F_STs between populations showed differentiation among mainland populations, while SCD displayed high levels of divergence (F_ST > 0.15) from most mainland populations. There was no significant isolation by distance among colonies. Most populations showed signs of a bottleneck effect.

Main conclusions

Our study suggests that there was no significant difference in the genetic diversity among the islands and the mainland; however, the lower genetic diversity, the higher degree of genetic divergence from other colonies, and the higher relatedness among nestmates made the SCD population stand out from all the others.     

Investigation of Mannheimia haemolytica bacteriophages relative to host diversity

Aims

This study aimed to characterize the impact of lytic and temperate bacteriophages on the genetic and phenotypic diversity of Mannheimia haemolytica from feedlot cattle.

Methods and Results

Strictly lytic phages were not detected from bovine nasopharyngeal (n = 689) or water trough (n = 30) samples, but Myoviridae‐ or Siphoviridae‐like phages were induced from 54 of 72 M. haemolytica strains by mitomycin C, occasionally from the same strain. Phages with similar restriction fragment length polymorphism profiles (RFLP ≥70% relatedness) shared common host serotypes 1 or 2 (P < 0·000 1). Likewise, phages with similar RFLP tended to occur in genetically related host bacteria (70–79% similarity). Host range assays showed that seven phages from host serotypes 1, 2 and 6 lysed representative strains of serotypes 1, 2 or 8. The genome of vB_MhM_1152AP from serotype 6 was found to be collinear with P2‐like phage φMhaA1‐PHL101.

Conclusions

Prophages are a significant component of the genome of M. haemolytica and contribute significantly to host diversity. Further characterization of the role of prophage in virulence and persistence of M. haemolytica in cattle could provide insight into approaches to control this potential respiratory pathogen.

Significance and Impact of the Study

This study demonstrated that prophages are widespread within the genome of M. haemolytica isolates and emphasized the challenge of isolating lytic phage as a therapeutic against this pathogen.     

Brief report: Lactobacillus bulgaricus GLB44 (Proviotic™) plus esomeprazole for Helicobacter pylori eradication: A pilot study

Background

Recent studies of Lactobacillus delbrueckii subsp. bulgaricus GLB44 plus a proton‐pump inhibitor (PPI) reported cures of more than 90% of patients with active Helicobacter pylori infections.

Aim

To confirm the high H. pylori cure rates reported previously.

Method

A pilot study was done in healthy H. pylori‐infected volunteers using 3‐gram sachet (3 billion cells) of L. delbrueckii GLB44 plus 22.3 mg of esomeprazole b.i.d., for 14 days. The result was determined by urea breath testing 4 weeks after therapy. Stopping rules required for ending enrollment if less than 3 of the first 10 subjects were cured.

Results

Nine subjects were entered and because all failed to achieve negative urea breath test, the stopping rule required the study to end.

Conclusion

We were unable to confirm reports of achieving a high H. pylori cure rate with L. delbrueckii GLB44 plus a PPI.     

Applying the polio model to New Zealand: The contingent role of socioeconomic status in infectious disease mortality

Objectives

The traditional polio model depicts a positive relationship between the disease and socioeconomic status (SES), with higher SES associated with exposure to the poliovirus beyond infancy/early childhood and a higher mortality rate. This study uses occupation data from non-Māori New Zealand death registrations and the Census to assess evidence for differential mortality by SES during the polio epidemics of 1916, 1924–25, and 1936–37.

Materials and Methods

Polio deaths were classified by father's occupation using the Caversham Project scheme, which includes nine collapsible urban occupational strata and codes rural occupations separately. Evidence for differential mortality and differences in age at death between rural and urban areas and among urban occupational strata was assessed using nonparametric Mann–Whitney U, Kruskal–Wallis, Jonckheere-Terpstra, and chi-square tests.

Results

There was limited evidence of either differential mortality or differences in age at death among collapsed urban strata, mainly in 1924/25, only partially meeting the expectations of the traditional polio model. For 1916 only, the rural group had a higher proportion of deaths (χ² (1, n = 95) = 8.341, p = 0.0039, φ = 0.30)) and higher age at death (U = 828.00, p = 0.026, r = −0.23).

Discussion

These results suggest that rural New Zealand was more isolated from poliovirus infection prior to 1916, but thereafter rural and urban groups faced more similar exposure patterns and mortality—at least among non-Māori. The degree to which occupational categories reflect conditions of exposure requires further research.

     

MIF‐173G/C (rs755622) polymorphism as a risk factor for acute lymphoblastic leukemia development in children

Background

Macrophage inhibitory factor (MIF) is a pro‐inflammatory cytokine modulating monocyte motility and a pleiotropic regulator of different biological and cellular processes. The MIF‐173G/C (rs755622) polymorphism is found in the promoter region and affects its activity. The present study investigated the MIF polymorphism as a risk factor for the development of acute lymphoblastic leukemia (ALL) in Egyptian children.

Methods

We analyzed the MIF‐173G/C (rs755622) polymorphism in 180 ALL cases and 150 healthy control children by amplification of the gene using a polymerase chain reaction followed by restriction endonuclease digestion and running on an agarose gel for visualization of the product.

Results

We found a significant incidence of the homozygous polymorphic (CC) genotype and the combined polymorphic genotypes (GC + CC) in ALL patients compared to healthy controls (p = 0.001 and p = 0.007, respectively), whereas the wild‐type genotype (GG) was more common in healthy controls (p = 0.006). Multivariate logistic regression analysis adjustment for MIF different genotypes and other potential risk factors such as age, sex and parental smoking indicated that the CC genotype is the only significant risk factor for the test (p = 0.02). We also noted that, by increasing the C‐allele representation within the gene [GC, CC], there was an increase in total leukocytic count (p = 0.09 and p = 0.001, respectively) that may reflect the bad prognostic impact of the polymorphic allele, although further studies are needed.

Conclusions

The results of the present study indicate that the MIF‐173G/C (rs755622) polymorphism is a risk factor for childhood ALL development with respect to both homozygous and combined polymorphic genotypes. In addition, the increased leukocytic count in synchronization with the increased representation of the polymorphic C‐allele may reflect its bad prognostic impact.     

Effect of <Emphasis Type="Italic">HXT</Emphasis> 1 and <Emphasis Type="Italic">HXT</Emphasis> 7 hexose transporter overexpression on wild-type and lactic acid producing <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> cells

Background  

Since about three decades, Saccharomyces cerevisiae can be engineered to efficiently produce proteins and metabolites. Even recognizing that in baker's yeast one determining step for the glucose consumption rate is the sugar uptake, this fact has never been conceived to improve the metabolite(s) productivity.     

Molecular and physiological comparison of spoilage wine yeasts

Aims

Dekkera bruxellensis and Pichia guilliermondii are contaminating yeasts in wine due to the production of phenolic aromas. Although the degradation pathway of cinnamic acids, precursors of these phenolic compounds has been described in D. bruxellensis, no such pathway has been described in P. guilliermondii.

Methods and Results

A molecular and physiological characterization of 14 D. bruxellensis and 15 P. guilliermondii phenol‐producing strains was carried out. Both p‐coumarate decarboxylase (CD) and vinyl reductase (VR) activities, responsible for the production of volatile phenols, were quantified and the production of 4‐vinylphenol and 4‐ethylphenol were measured. All D. bruxellensis and some P. guilliermondii strains showed the two enzymatic activities, whilst 11 of the 15 strains of this latter species showed only CD activity and did not produce 4‐EP in the assay conditions. Furthermore, PCR products obtained with degenerated primers showed a low homology with the sequence of the gene for a phenyl acrylic acid decarboxylase activity described in Saccharomyces cerevisiae.

Conclusions

D. bruxellensis and P. guilliermondii may share a similar metabolic pathway for the degradation of cinnamic acids.

Significance and Impact of the Study

This is the first work that analyses the CD and VR activities in P. guilliermondii, and the results suggest that within this species, there are differences in the metabolization of cinnamic acids.     

Recombination and selectional forces in cyanopeptolin NRPS operons from highly similar,but geographically remote <Emphasis Type="Italic">Planktothrix</Emphasis> strains

Background  

Cyanopeptolins are nonribosomally produced heptapetides showing a highly variable composition. The cyanopeptolin synthetase operon has previously been investigated in three strains from the genera Microcystis, Planktothrix and Anabaena. Cyanopeptolins are displaying protease inhibitor activity, but the biological function(s) is (are) unknown. Cyanopeptolin gene cluster variability and biological functions of the peptide variants are likely to be interconnected.     

Attenuation of a virulent Aeromonas hydrophila with novobiocin and pathogenic characterization of the novobiocin‐resistant strain

Aim

To determine whether novobiocin resistance strategy could be used to attenuate a virulent Aeromonas hydrophila AH11P strain and to characterize the growth and pathogenic differences between the novobiocin‐resistant strain and its virulent parent strain AH11P.

Methods and Results

A novobiocin‐resistant strain AH11NOVO was obtained from a virulent Aer. hydrophila strain AH11P through selection of resistance to novobiocin. AH11NOVO was found to be avirulent to channel catfish (Ictalurus punctatus), whereas AH11P was virulent. When AH11NOVO vaccinated channel catfish were challenged with AH11P at 14 days postvaccination, relative per cent of survival of vaccinated fish was 100%. The cell proliferation rate of AH11NOVO was found to be significantly (P < 0·05) less than that of AH11P. In vitro motility assay revealed that AH11NOVO was nonmotile, whereas AH11P was motile. AH11NOVO had significantly (P < 0·05) lower in vitro chemotactic response to catfish mucus than that of AH11P. Although the ability of AH11NOVO to attach catfish gill cells was similar to that of AH11P, the ability of AH11NOVO to invade catfish gill cells was significantly (P < 0·05) lower than that of AH11P.

Conclusions

The novobiocin‐resistant AH11NOVO is attenuated and different from its parent AH11P in pathogenicity.

Significance and Impact of the Study

The significantly lower chemotactic response and invasion ability of AH11NOVO compared with that of its virulent parent strain AH11P might shed light on the pathogenesis of Aer. hydrophila.     

Neuraminidase Inhibitors from marine‐derived actinomycete Streptomyces seoulensis

Aims

This work was performed to characterize new secondary metabolites with neuraminidase (NA) inhibitory activity from marine actinomycete strains.

Methods and Results

An actinomycete strain IFB‐A01, capable of producing new NA inhibitors, was isolated from the gut of shrimp Penasus orientalis and identified as Streptomyces seoulensis according to its 16S rRNA sequence (over 99% homology with that of the standard strain). Repeated chromatography of the methanol extract of the solid‐substrate culture of S. seoulensis IFB‐A01 led to the isolation of streptoseolactone ( 1 ), and limazepines G ( 2 ) and H ( 3 ). The structures of 1 – 3 were determined by a combination of IR, ESI‐MS, 1D (¹H and ¹³C NMR, and DEPT) and 2D NMR experiments (HMQC, HMBC, ¹H‐¹H COSY and NOESY). Compounds 1 – 3 showed significant inhibition on NA in a dose‐dependent manner with IC₅₀ values of 3·92, 7·50 and 7·37 μmol l^?1, respectively.

Conclusions

This is the first report of two new ( 1 and 2 ) and known ( 3 , recovered as a natural product for the first time in the work) NA inhibitors from the marine‐derived actinomycete S. seoulensis IFB‐A01.

Significance and Impact of the Study

The three natural NA inhibitors maybe of value for the development of drug(s) necessitated for the treatment of viral infections.