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The Entner–Doudoroff (ED) pathway provides an alternative to glycolysis. It converts 6-phosphogluconate (6-PG) to glyceraldehyde-3-phosphate and pyruvate in two steps consisting of a dehydratase (EDD) and an aldolase (EDA). Here, we investigate its distribution and significance in higher plants and determine the ED pathway is restricted to prokaryotes due to the absence of EDD genes in eukaryotes. EDDs share a common origin with dihydroxy-acid dehydratases (DHADs) of the branched chain amino acid pathway (BCAA). Each dehydratase features strict substrate specificity. E. coli EDD dehydrates 6-PG to 2-keto-3-deoxy-6-phosphogluconate, while DHAD only dehydrates substrates from the BCAA pathway. Structural modeling identifies two divergent domains which account for their non-overlapping substrate affinities. Coupled enzyme assays confirm only EDD participates in the ED pathway. Plastid ancestors lacked EDD but transferred metabolically promiscuous EDA, which explains the absence of the ED pathway from the Viridiplantae and sporadic persistence of EDA genes across the plant kingdom. The Enter-Doudoroff (ED) pathway is an alternative to glycolysis present in some prokaryotes. Evans et al. show that its dehydratase enzyme, evolved from a branched chain amino acid pathway paralog, acquired a new function through mutations in its active site.

Salicylic acid (SA) is produced by plants in response to pathogen infection. SA binds the NONEXPRESSOR OF PATHOGENESIS-RELATED GENES (NPR) family of receptors to regulate both positive (NPR1) and negative (NPR3/4) plant immune responses by interacting with the clade II TGACG (TGA) motif-binding transcription factors (TGA2, TGA5, and TGA6). Here, we report that the principal metabolome-level response to SA treatment in Arabidopsis is a reduction in sucrose and other free sugars. We observed nearly identical effects in the tga256 triple mutant, which lacks all clade II TGA transcription factors. The tga256 mutant presents reduced leaf blade development and elongated hypocotyls, roots, and petioles consistent with sucrose starvation. No changes were detected in auxin levels, and mutant seedling growth could be restored to that of wild-type by sucrose supplementation. Although the retrograde signal 2-C-methyl-D-erythritol-2,4-cyclodiphosphate is known to stimulate SA biosynthesis and defense signaling, we detected no negative feedback by SA on this or any other intermediate of the 2-C-methyl-D-erythritol-4-phosphate pathway. Trehalose, a proxy for the sucrose regulator trehalose-6-phosphate (T6P), was highly reduced in tga256, suggesting that defense-related reductions in sugar availability may be controlled by changes in T6P levels. We conclude that the negative regulatory roles of TGA2/5/6 include maintaining sucrose levels in healthy plants. Disruption of TGA2/5/6-NPR3/4 inhibitory complexes by mutation or SA triggers sucrose reductions in Arabidopsis leaves, consistent with the ‘pathogen starvation’ hypothesis. These findings highlight sucrose availability as a mechanism by which TGA2/5/6 balance defense and development.

Monoterpenoids are C 10 isoprenoid natural products with diverse functions as volatile and non-volatile secondary metabolites. Their biosynthesis from acyclic diphosphate precursors is often accompanied by one or more ring closures, which stabilize the linear, carbocationic intermediates generated during typical terpene synthase reaction sequences. The subset that remains uncyclized following the elimination of the diphosphate group correspondingly retains higher reactivity than their cyclized counterparts, a property that may explain the additional transformations that geraniol and other acyclics undergo to yield monoterpene aldehydes, acids, esters, glycosides, and iridoids, many of which possess allelochemical activity as pollinator attractants, feeding deterrents, or insect repellents. Essential oils of lemon grass (or citronella) ( Cymbopogon ), rose-scented geraniums ( Pelargonium ), and lemon-scented gums ( Corymbia ) are rich sources of the acyclic monoterpene alcohols we collectively refer to in this review as ‘citronelloids’. Their formation from geranyl diphosphate may be brought about by the tps-g or tps-b subclade of terpene synthases or, alternatively, by a subclade of Nudix hydrolases which act preferentially on prenyl diphosphate substrates, yielding monoterpene alcohols in a two step process that involves a monophosphate intermediate. In some members of the Lamiid and Campanulid clades, further oxidation of geraniol and a non-classical, reductive cyclization leads to the iridoids, a group of mostly non-volatile, bicyclic monoterpenes with potent anti-herbivory and anti-inflammatory properties. Here we review the recent literature on acyclic monoterpene biosynthesis, their natural distribution across the plant kingdom, and their emerging roles in medicine as biologically active natural products.

Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3 R451C , Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of Bilophila , Clostridium , Dorea and Lactobacillus and a decrease in Blautia genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including Akkermansia , Bacteroides , Bifidobacterium , Parabacteroides and Prevotella , suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.

Objective Hospitals serve as hotspots of antibiotic resistance. Despite several studies exploring antibiotic resistance in hospitals, none have explored the resistance profile of soil bacteria from a hospital precinct. This study examined and compared the antibiogram of the soil isolates from a hospital and its affiliated university precinct, to determine if antibiotic resistant bacteria were present closer to the hospital. Results 120 soil samples were collected from JSS Hospital and JSS University in Mysore, India across three consecutive seasons (monsoon, winter and summer). 366 isolates were randomly selected from culture. Antibiotic susceptibility testing was performed on 128 isolates of Pseudomonas (n = 73), Acinetobacter (n = 30), Klebsiella species (n = 15) and Escherichia coli (n = 10). Pseudomonas species exhibited the highest antibiotic resistance. Ticarcillin-clavulanic acid, an extended-spectrum carboxypenicillin antibiotic used to treat moderate-to-severe infections, ranked highest amongst the antibiotics to whom these isolates were resistant (n = 51 out of 73, 69.9%). Moreover, 56.8% (n = 29) were from the hospital and 43.1% (n = 22) were from the university precinct, indicating antibiotic resistant bacteria were closer to the hospital setting. This study highlights the effect of antibiotic usage in hospitals and the influence of anthropogenic activities in the hospital on the dissemination of antibiotic resistance into hospital precinct soil.

Soil contains an enormous diversity of microorganisms and can act as a reservoir of antibiotic resistance determinants. This study identified and compared the bacterial diversity and the antimicrobial resistance profile of clinically-relevant isolates around a newly developed hospital and university precinct. Eight soil samples were collected, genomic DNA was extracted and 16S rRNA gene sequencing was performed. Bacterial isolates cultured from the soil were identified using MALDI-TOF. Antibiotic sensitivity testing (AST) was performed on a subset of isolates. The soil from both precincts were similarly diverse. Phylum Proteobacteria was prevalent in all samples and was the most abundant in one of the hospital sites. Cyanobacteria was abundant in two hospital sites closer to a sewage treatment plant. Bacterial diversity was only significantly different between two of the hospital sites. A total of 22 Gram-negative organisms were isolated by culture. AST revealed that the soil isolates from both precincts exhibited low resistance. The unidentified bacteria closer to the hospital precinct with human interactions possibly hints at the role of anthropogenic activities on the soil microbial diversity. The abundance of Proteobacteria (causing majority of human infections) and Cyanobacteria nearer to the hospital premises, comprising more immunocompromised and immunocompetent individuals, is concerning.

Cerebral malaria (CM) is the most severe form of malaria with the highest mortality rate and can result in life-long neurological deficits and ongoing comorbidities. Factors contributing to severity of infection and development of CM are not fully elucidated. Recent studies have indicated a key role of the gut microbiome in a range of health conditions that affect the brain, but limited microbiome research has been conducted in the context of malaria. To address this knowledge gap, the impact of CM on the gut microbiome was investigated in mice. C57BL/6J mice were infected with Plasmodium berghei ANKA (PbA) parasites and compared to non-infected controls. Microbial DNA from faecal pellets collected daily for 6-days post-infection were extracted, and microbiome comparisons conducted using 16S rRNA profiling. We identified significant differences in the composition of bacterial communities between the infected and the non-infected groups, including a higher abundance of the genera Akkermansia , Alistipes and Alloprevotella in PbA-infected mice. Furthermore, intestinal samples were collected post-cull for morphological analysis. We determined that the caecal weight was significantly lower, and the small intestine was significantly longer in PbA-infected mice than in the non-infected controls. We concluded that changes in microbial community composition were primarily driven by the infection protocol and, to a lesser extent, by the time of infection. Our findings pave the way for a new area of research and novel intervention strategies to modulate the severity of cerebral malaria disease.

Gastrointestinal (GI) dysfunction is a common comorbidity of autism spectrum disorders (ASD) and is associated with increased severity of characteristic autism-associated symptoms. However, the underlying biological mechanisms for GI dysfunction symptoms in children with ASD are unknown. This review explores potential explanations for these symptoms including altered enteric microbiota, impaired intestinal permeability, changes in immune homeostasis, and genetic factors such as single nucleotide polymorphisms. It was shown that genetic factors not only influence the development of altered enteric microbiota and impaired intestinal permeability, but also are a strong, independent contributor to GI dysfunction in ASD patients.

Pelvic floor disorders, including pelvic organ prolapse and stress urinary incontinence, are prevalent health concerns, affecting approximately 50% of females over their lifetime, with about 75% of women over 65 years of age being impacted. Traditional surgical interventions, such as transvaginal mesh implants, have led to numerous complications, resulting in their prohibition in several countries. This study introduces an innovative composite mesh designed to mitigate these issues by combining polymethylmethacrylate and thermoplastic polyurethane, further enhanced with iodine-doped carbon nanoparticles to enable visibility via medical imaging. The mesh is coated with 2-methacryloyloxyethyl phosphorylcholine polymer to prevent protein adsorption and promote tissue regeneration. In vitro studies showed high cell viability and low protein adsorption, indicating excellent biocompatibility. Implantation of mesh (with or without iodine) in mice revealed no adverse effects on overall animal health. Mouse spleen weight (an indicator of inflammation) was similar between groups; however, levels of some cytokines (i.e., IL-10, IL-17A and GM-CSF) were elevated following implantation of iodinated mesh in mice suggesting that further refinement of the composite mesh is required. Analysis of the fecal microbiome, which is correlated with physiological states, showed that sham and iodinated mesh implant groups maintained consistent microbial profiles with stable diversity (richness and evenness) measures over time. In contrast, the non-iodinated mesh group exhibited decreased species richness post mesh implantation, likely due to a distinct starting microbiome composition prior to implantation. This research is envisaged to contribute to a safer and more effective solution for treating pelvic floor disorders, providing non-invasive post-implantation monitoring and enhanced mechanical compatibility of surgical mesh with native tissue. Our findings demonstrate that this composite mesh possesses mechanical properties that closely mimic human tissue, ensuring biocompatibility, strength, and flexibility without stimulating significant inflammatory or foreign body responses.Competing Interest StatementThe authors have declared no competing interest.