Antibacterial activities of the methanol extracts of Albizia adianthifolia,Alchornea laxiflora,Laportea ovalifolia and three other Cameroonian plants against multi-drug resistant Gram-negative bacteria

In the last 10 years, resistance in Gram-negative bacteria has been increasing. The present study was designed to evaluate the in vitro antibacterial activities of the methanol extracts of six Cameroonian medicinal plants Albizia adianthifolia, Alchornea laxiflora, Boerhavia diffusa, Combretum hispidum, Laportea ovalifolia and Scoparia dulcis against a panel of 15 multidrug resistant Gram-negative bacterial strains. The broth microdilution was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts. The preliminary phytochemical screening of the extracts was conducted according to the reference qualitative phytochemical methods. Results showed that all extracts contained compounds belonging to the classes of polyphenols and triterpenes, other classes of chemicals being selectively distributed. The best antibacterial activities were recorded with bark and root extracts of A. adianthifolia as well as with L. ovalifolia extract, with MIC values ranging from 64 to 1024 μg/mL on 93.3% of the fifteen tested bacteria. The lowest MIC value of 64 μg/mL was recorded with A. laxiflora bark extract against Enterobacter aerogenes EA289.Finally, the results of this study provide evidence of the antibacterial activity of the tested plants and suggest their possible use in the control of multidrug resistant phenotypes.     

A framework for how environment contributes to cancer risk

Evolutionary theory explains why metazoan species are largely protected against the negative fitness effects of cancers. Nevertheless, cancer is often observed at high incidence across a range of species. Although there are many challenges to quantifying cancer epidemiology and assessing its causes, we claim that most modern‐day cancer in animals – and humans in particular – are due to environments deviating from central tendencies of distributions that have prevailed during cancer resistance evolution. Such novel environmental conditions may be natural and/or of anthropogenic origin, and may interface with cancer risk in numerous ways, broadly classifiable as those: increasing organism body size and/or life span, disrupting processes within the organism, and affecting germline. We argue that anthropogenic influences, in particular, explain much of the present‐day cancer risk across life, including in humans. Based on a literature survey of animal species and a parameterised mathematical model for humans, we suggest that combined risks of all cancers in a population beyond c. 5% can be explained to some extent by the influence of novel environments. Our framework provides a basis for understanding how natural environmental variation and human activity impact cancer risk, with potential implications for species ecology.     

Food webs obscure the strength of plant diversity effects on primary productivity

Plant diversity experiments generally find that increased diversity causes increased productivity; however, primary productivity is typically measured in the presence of a diverse food web, including pathogens, mutualists and herbivores. If food web impacts on productivity vary with plant diversity, as predicted by both theoretical and empirical studies, estimates of the effect of plant diversity on productivity may be biased. We experimentally removed arthropods, foliar fungi and soil fungi from the longest‐running plant diversity experiment. We found that fungi and arthropods removed a constant, large proportion of biomass leading to a greater reduction of total biomass in high diversity plots. As a result, the effect of diversity on measured plant productivity was much higher in the absence of fungi and arthropods. Thus, diversity increases productivity more than reported in previous studies that did not control for the effects of heterotrophic consumption.     

Mechanisms and functions of guanylate‐binding proteins and related interferon‐inducible GTPases: Roles in intracellular lysis of pathogens

Guanylate‐binding proteins (GBPs) are a group interferon‐inducible GTPases within the constellation of the dynamin GTPase superfamily. These proteins restrict the replication of intracellular pathogens in both immune and non‐immune cells. GBPs and their related family members immunity‐related GTPases target and lyse the membrane of the pathogen‐containing vacuole, destroying the residential niche of vacuolar protozoal and bacterial pathogens. They also prevent virion infectivity and target replication complexes of ribonucleic acid viruses. The exciting concept that GBPs and immunity‐related GTPases can directly target the membrane of bacteria and protozoa has emerged. Rupture and lysis of the pathogen membrane mediates liberation of concealed microbial ligands for activation of innate immune sensing pathways and the inflammasome. Further studies have demonstrated a capacity of GBPs to recruit additional antimicrobial factors, highlighting the complexity of the molecular mechanisms involved in pathogen killing. In this mini‐review, we discuss recent advances describing the localisation and functions of GBPs on the host and pathogen membrane. We also highlight unresolved questions related to the regulation of GBPs in cell‐autonomous immunity to intracellular pathogens.     

Genotype specificity among hosts,pathogens, and beneficial microbes influences the strength of symbiont‐mediated protection

The microbial symbionts of eukaryotes influence disease resistance in many host‐parasite systems. Symbionts show substantial variation in both genotype and phenotype, but it is unclear how natural selection maintains this variation. It is also unknown whether variable symbiont genotypes show specificity with the genotypes of hosts or parasites in natural populations. Genotype by genotype interactions are a necessary condition for coevolution between interacting species. Uncovering the patterns of genetic specificity among hosts, symbionts, and parasites is therefore critical for determining the role that symbionts play in host‐parasite coevolution. Here, we show that the strength of protection conferred against a fungal pathogen by a vertically transmitted symbiont of an aphid is influenced by both host‐symbiont and symbiont‐pathogen genotype by genotype interactions. Further, we show that certain symbiont phylogenetic clades have evolved to provide stronger protection against particular pathogen genotypes. However, we found no evidence of reciprocal adaptation of co‐occurring host and symbiont lineages. Our results suggest that genetic variation among symbiont strains may be maintained by antagonistic coevolution with their host and/or their host's parasites.     

Roq1 mediates recognition of the Xanthomonas and Pseudomonas effector proteins XopQ and HopQ1

Xanthomonas spp. are phytopathogenic bacteria that can cause disease on a wide variety of plant species resulting in significant impacts on crop yields. Limited genetic resistance is available in most crop species and current control methods are often inadequate, particularly when environmental conditions favor disease. The plant Nicotiana benthamiana has been shown to be resistant to Xanthomonas and Pseudomonas due to an immune response triggered by the bacterial effector proteins XopQ and HopQ1, respectively. We used a reverse genetic screen to identify Recognition of XopQ 1 (Roq1), a nucleotide‐binding leucine‐rich repeat (NLR) protein with a Toll‐like interleukin‐1 receptor (TIR) domain, which mediates XopQ recognition in N. benthamiana. Roq1 orthologs appear to be present only in the Nicotiana genus. Expression of Roq1 was found to be sufficient for XopQ recognition in both the closely‐related Nicotiana sylvestris and the distantly‐related beet plant (Beta vulgaris). Roq1 was found to co‐immunoprecipitate with XopQ, suggesting a physical association between the two proteins. Roq1 is able to recognize XopQ alleles from various Xanthomonas species, as well as HopQ1 from Pseudomonas, demonstrating widespread potential application in protecting crop plants from these pathogens.     

Compound design guidelines for evading the efflux and permeation barriers of Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole cell Gram-negative activity

Previously we reported the results from an effort to improve Gram-negative antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chemistry campaign focused entirely on C-ring modifications. In that series we set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-negative activity: i) low MW (<400), ii) high polarity (clogD_7.4 <1), and iii) zwitterionic character at pH 7.4. Indeed, we observed that only analogs residing within these limits were able to overcome these barriers. Herein we report the results from a parallel effort where we explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, analysis of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ≤4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts.     

Structure-activity relationship-based screening of antibiotics against Gram-negative Acinetobacter baumannii

To discover potent antibiotics against the Gram-negative bacteria, we performed a structure-activity relationship (SAR) study of YKsa-6, which was the most potent inhibitor of Staphylococcus aureus β-ketoacyl acyl carrier protein III in our previous study. We identified and selected 11 candidates, and finally screened two active compounds, YKab-4 (4-[(3-chloro-4-methylphenyl)aminoiminomethyl]benzene-1,3-diol) and YKab-6 (4-[[3-(trifluoromethyl)phenyl]aminoiminomethyl]phenol) as inhibitors of Acinetobacter baumannii KAS III (abKAS III). They showed potent antimicrobial activities at 2 or 8 μg/mL, specifically against Acinetobacter baumannii and a strong binding affinity for abKAS III. From the homology modeling, we defined the three-dimensional (3D) structure of abKAS III for the first time and found that it had an extra loop region compared with common Gram-negative bacteria derived KAS IIIs. The docking study revealed that the hydroxyl groups of inhibitors formed extensive hydrogen bonds and the complicated hydrophobic and cation-stacking interactions are important to binding with abKAS III. We confirmed that the hydrophobicity of these compounds might be the essential factor for their antimicrobial activities against Gram-negative bacteria as well as their structural rigidity, a cooperative feature for retaining the hydrophobic interactions between abKAS III and its inhibitors. This study may provide an insight developing strategies for potent antibiotics against A. baumannii.     

The role of nutrition, crowding and interspecific interactions in the development of winged aphids

1. Winged morph production in aphids is a phenotypic trait that has traditionally been seen as a response to unfavourable environmental conditions. The evidence to support this theory is reviewed and the ecological and evolutionary significance of the findings is discussed. 2. The common assertion of poor host‐plant nutritional quality leading to increased production of winged morphs does not always apply, particularly when the host‐plant quality is exceptionally poor. The available data are skewed heavily towards Myzus persicae, and for this species the dynamical change in plant quality appears to be important with respect to wing induction. 3. Crowding may be a less influential stimulus for wing induction as study methods approach natural conditions experienced by aphids on their host plant. 4. The growing evidence that interactions with other organisms can induce the production of winged morphs by aphid colonies is reviewed. In the case of natural enemies, such a response by an aphid colony may be regarded as induced defence. Wing induction may also act as a means of transmission for a virus or fungal pathogen.