Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies

Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources.     

Hemodynamic effects of incremental doses of acepromazine in isoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of incremental doses of acepromazine on hemodynamics in isoflurane-anesthetized dogs.Study designProspective, experimental study.AnimalsHealthy, adult, mixed-breed dogs (two male and four female) weighing 16.8 ± 5.1 kg (mean ± standard deviation).MethodsDogs were anesthetized with propofol (7 mg kg^–1) intravenously (IV) and isoflurane. Thermodilution and arterial catheters were placed for hemodynamic monitoring and arterial blood sampling for blood gas analysis. Baseline measurements were performed with stable expired concentration of isoflurane (Fe′Iso) at 1.8%. Each dog was then administered four incremental acepromazine injections (10, 15, 25 and 50 μg kg^–1) IV, and measurements were repeated 20 minutes after each acepromazine injection with Fe′Iso decreased to 1.2%. The four acepromazine injections resulted in cumulative doses of 10, 25, 50 and 100 μg kg^–1 (time points ACP₁₀, ACP₂₅, ACP₅₀ and ACP₁₀₀, respectively).ResultsCompared with baseline, cardiac index (CI) increased significantly by 34%, whereas systemic vascular resistance index (SVRI) decreased by 25% at ACP₅₀ and ACP₁₀₀. Arterial oxygen content (CaO₂) was significantly lower than baseline after all acepromazine injections (maximum decreases of 11%) and was lower at ACP₅₀ and ACP₁₀₀ than at ACP₁₀. No significant change was found in heart rate, stroke index, oxygen delivery index and systolic, mean and diastolic blood pressures. Hypotension (mean arterial pressure < 60 mmHg) was observed in one dog at baseline, ACP₁₀, ACP₂₅ and ACP₁₀₀, and in two dogs at ACP₅₀.Conclusions and clinical relevanceCompared with isoflurane alone, anesthesia with acepromazine–isoflurane resulted in increased CI and decreased SVRI and CaO₂ values. These effects were dose-related, being more pronounced at ACP₅₀ and ACP₁₀₀. Under the conditions of this study, acepromazine administration did not change blood pressure.     

Ace and ace-like genes of invasive redlegged earth mite: copy number variation,target-site mutations,and their associations with organophosphate insensitivity

Background

Invasive Australian populations of redlegged earth mite, Halotydeus destructor (Tucker), are evolving increasing organophosphate resistance. In addition to the canonical ace gene, the target gene of organophosphates, the H. destructor genome contains many radiated ace-like genes that vary in copy number and amino acid sequence. In this work, we characterise copy number and target-site mutation variation at the canonical ace and ace-like genes and test for potential associations with organophosphate insensitivity. This was achieved through comparisons of whole-genome pool-seq data from alive and dead mites following organophosphate exposure.

Results

A combination of increased copy number and target-site mutations at the canonical ace was associated with organophosphate insensitivity in H. destructor. Resistant populations were segregating for G119S, A201S, F331Y at the canonical ace. A subset of populations also had copy numbers of canonical ace > 2, which potentially helps overexpress proteins carrying these target-site mutations. Haplotypes possessing different copy numbers and target-site mutations of the canonical ace gene may be under selection across H. destructor populations. We also detected some evidence that increases in copy number of radiated ace-like genes are associated with organophosphate insensitivity, which might suggest potential roles in sequestration or breakdown of organophosphates.

Conclusion

Different combinations of target-site mutations and (or) copy number variation in the canonical ace and ace-like genes may provide non-convergent ways for H. destructor to respond to organophosphate selection. However, these changes may only play a partial role in organophosphate insensitivity, which appears to have a polygenic architecture. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Genome-wide in silico analysis of SOD genes in common bean (Phaseolus vulgaris L.)

Journal of Crop Science and Biotechnology - Superoxide dismutases (SODs) are a group of enzymes that play essential roles in catalyzing the dismutation of superoxide radicals to protect cells from...     

Meta-analysis of fungicide efficacy on soybean target spot and cost–benefit assessment

Target spot of soybean has spread in Brazil, the southeastern United States and Argentina in the last decade. A collaborative network of field Uniform Fungicide Trials (UFT) in Brazil was created in 2011 to study the target spot control efficacy of fungicides, including azoxystrobin + benzovindiflupyr (AZ_BF), carbendazim (CZM), fluxapyroxad + pyraclostrobin (FLUX_PYRA), epoxiconazole + FLUX_PYRA (EPO_FLUX_PYRA), mancozeb (MZB) and prothioconazole + trifloxystrobin (PROT_TRIF). Network meta-analysis was used to conduct a quantitative synthesis of UFT data collected from 2012 to 2016 and to evaluate the effects of disease pressure (DP, low ≤ 35% target spot severity in the nontreated control < high) and year of experiment on the overall mean efficacy and yield response to each of the tested fungicides. Based on mean percentage control of target spot severity, the tested fungicides fall into three efficacy groups (EG): high EG, FLUX_PYRA (76.2% control relative to the nontreated control) and EPO_FLUX_PYRA (75.7% control); intermediate EG, PROT_TRIF (66.5% control) and low EG, MZB (49.6% control), AZ_BF (46.7% control) and CZM (32.4% control). DP had a significant effect on yield response. At DP_Low, the highest response was due to PROT_TRIF (+342 kg ha⁻¹, +12.8%) and EPO_FLUX_PYRA (+295.5 kg ha⁻¹, +11.2%), whereas at DP_High, EPO_FLUX_PYRA and FLUX_PYRA outperformed the other treatments, with yield responses of 503 kg ha⁻¹ (+20.2%) and 469 kg ha⁻¹ (+19.1%), respectively. The probability of a positive return on fungicide investment ranged from 0.26 to 0.56 at DP_Low and from 0.34 to 0.66 at DP_High.     

Differences in swimbladder volume between Baltic and Norwegian spring-spawning herring: Consequences for mean target strength

Fish swimbladders, where present, contribute most to the scattering of sound by fish, as measured by the target strength (TS). The volumes of the swimbladders of two different European stocks of Atlantic herring were compared to consider the effect on estimates of TS. Swimbladder volumes of Baltic and Norwegian spring-spawning herring (Clupea harengus) were measured, together with individual herring fat content. Swimbladder volumes were found to differ significantly between the two herring stocks. Baltic herring have a larger swimbladder volume, which is suggested to be associated with the fish's low fat content, which in turn may be linked to its specific energy budget and the low salinity of the Baltic Sea. A buoyancy model that considered the different salinity conditions and fat proportions was used to evaluate the observed differences in swimbladder volume. The swimbladder volume data were subsequently used to model the mean target strength as a function of depth and growth pattern. Backscattering of the swimbladder was modelled using the modal-series-based deformed-cylinder model (MSB-DCM), describing the swimbladder as a gas-filled, elongated prolate spheroid. The fish body component was modelled as a fluid-filled ellipsoid using the distorted wave Born approximation (DWBA). Modelling results support a different TS-to-size relationship for Baltic herring, with a stronger echo, due to the larger swimbladder. Depth- and length-dependent TS relationships based on the model results are suggested.     

A 3-year assessment of nitrous oxide emission factors for urine and dung of grazing sheep in a subtropical ecosystem

Purpose

Grazing livestock has strong impact on global nitrous oxide (N₂O) emissions by providing N sources through excreta. The scarcity of information on factors influencing N₂O emissions from sheep excreta in subtropical ecosystems such as those of Southern Brazil led us to conduct field trials in three different winter pasture seasons on an integrated crop–livestock system (ICL) in order to assess N₂O emission factors (EF-N₂O) in response to variable rates of urine and dung.

Materials and methods

The equivalent urine-N loading rates for the three winter seasons (2009, 2010, and 2013) ranged from 96 to 478 kg ha^?1, and the dung-N rates applied in 2009 and 2010 were 81 and 76 kg ha^?1, respectively. Air was sampled from closed static chambers (0.20 m in diameter) for approximately 40 days after excreta application and analyzed for N₂O by gas chromatography.

Results and discussion

Soil N₂O-N fluxes spanned the ranges 4 to 353 μg m^?2 h^?1 in 2009, ??47 to 976 μg m^?2 h^?1 in 2010, and 46 to 339 μg m^?2 h^?1 in 2013. Urine addition resulted in N₂O-N peaks within for up to 20–30 days after application in the 3 years, and the strength of the peaks was linearly related to the N rate used. Emission factors of N₂O (EF-N₂O, % of N applied that is emitted as N₂O) of urine ranged from 0.06 to 0.34% and were essentially independent of N rate applied. By considering a ratio of N excreted by urine and dung of 60:40, a single combined excretal EF-N₂O of 0.14% was estimated.

Conclusions

Our findings showed higher mean EF-N₂O for sheep urine than that for dung (0.21% vs 0.03%), irrespective of the occurrence or not of urine patches overlap. This value is much lower than default value of 1% of IPCC’s Tier 1 and reinforces the needs of its revision.

     

Short-wave solar radiation level willingly tolerated by lactating Holstein cows in an equatorial semi-arid environment

The amount of short-wave solar radiation willingly tolerated by lactating Holstein cows on pasture was determined in an equatorial semi-arid environment. The study was carried out on a dairy farm located in Limoeiro do Norte, CE, northeastern Brazil. The observed behaviours were as follows: grazing, under the sun, under the shade, standing, lying, ruminating, idling and wallowing in the water. The behaviours were recorded using instantaneous scan sampling at regular intervals of 15 min from 0600 to 1800 hours over 5 days. On all sampling days, the meteorological variables, including local short-wave solar radiation (R _S-W, W m^?2), were recorded. The R _S-W data were divided into five levels. The sun exposure was more frequent under low (100 %) and moderately low (97 %) levels, when R _S-W remained below 500 W m^?2. The grazing was more intense under low (100 %) and moderately low (93 %) levels. Above 500 W m^?2, the grazing time significantly decreased (11 %). The cows avoided grazing under high (0 %) and very high (0 %) levels, when R _S-W exceeded 700 W m^?2. The ruminating behaviour was more frequent under high (33 %) and very high (37 %) levels, in which the highest averages of R _S-W were recorded (815 and 958 W m^?2, respectively). The standing posture was more frequent under low (100 %) and moderately low (97 %) levels. Therefore, the critical R _S-W level that motivates cows to stop grazing and seek shade was in the interval between 500 and 700 W m^?2.     

Immunohistochemical Expression of Growth Factors in the Follicular Wall of Normal and Cystic Ovaries of Sows

The expression of growth factors was evaluated immunohistochemically in normal and cystic ovaries of sows. The immunohistochemically stained area (IHCSA) was quantified by image analysis to analyse the expression of these proteins in the follicular wall of secondary, tertiary and cystic follicles. IGF‐I immunoreactivity was strong in the granulosa cell layer (GC), moderate in the theca interna (TI) and mild in the theca externa (TE) of the normal follicles. There was severe reduction of the labelling to IGF‐I in the GC of the follicular and luteinized cysts. In the normal follicles, the reactivity for IGF‐II was very similar to pattern noted in IGF‐I. There was reduction of the IHCSAs in the GC of the follicular and luteinized cysts, but the decrease was not significant. The staining of the IGF‐II in the TI and TE of the cysts was increased, in comparison with normal follicles. The IHCSAs for VEGF were higher in the GC and TE of the normal follicles in contrast to TI, but this difference was noted only in the tertiary follicle. The VEGF reactivity increased in the GC of the cysts, in relation to normal follicles. The results of the current study show that the formation of ovarian cysts in sows is associated with alterations in the immunohistochemical expression of some growth factors.