Bacterial biofilms in the human body: prevalence and impacts on health and disease.

Bacterial biofilms can be found in most environments on our planet, and the human body is no exception. Consisting of microbial cells encased in a matrix of extracellular polymers, biofilms enable bacteria to sequester themselves in favorable niches, while also increasing their ability to resist numerous stresses and survive under hostile circumstances. In recent decades, biofilms have increasingly been recognized as a major contributor to the pathogenesis of chronic infections. However, biofilms also occur in or on certain tissues in healthy individuals, and their constituent species are not restricted to canonical pathogens. In this review, we discuss the evidence for where, when, and what types of biofilms occur in the human body, as well as the diverse ways in which they can impact host health under homeostatic and dysbiotic states.

Prevalence and Correlates of Phenazine Resistance in Culturable Bacteria from a Dryland Wheat Field.

Phenazines are a class of bacterially produced redox-active natural antibiotics that have demonstrated potential as a sustainable alternative to traditional pesticides for the biocontrol of fungal crop diseases. However, the prevalence of bacterial resistance to agriculturally relevant phenazines is poorly understood, limiting both the understanding of how these molecules might shape rhizosphere bacterial communities and the ability to perform a risk assessment for off-target effects. Here, we describe profiles of susceptibility to the antifungal agent phenazine-1-carboxylic acid (PCA) across more than 100 bacterial strains isolated from a wheat field where PCA producers are indigenous and abundant. We found that Gram-positive bacteria are typically more sensitive to PCA than Gram-negative bacteria, and there was significant variability in susceptibility both within and across phyla. Phenazine-resistant strains were more likely to be isolated from the wheat rhizosphere, where PCA producers were also more abundant, compared to bulk soil. Furthermore, PCA toxicity was pH-dependent for most susceptible strains and broadly correlated with PCA reduction rates, suggesting that uptake and redox-cycling were important determinants of phenazine toxicity. Our results shed light on which classes of bacteria are most likely to be susceptible to phenazine toxicity in acidic or neutral soils. In addition, the taxonomic and phenotypic diversity of our strain collection represents a valuable resource for future studies on the role of natural antibiotics in shaping wheat rhizosphere communities. IMPORTANCE Microbial communities contribute to crop health in important ways. For example, phenazine metabolites are a class of redox-active molecules made by diverse soil bacteria that underpin the biocontrol of diseases of wheat and other crops. Their physiological functions are nuanced. In some contexts, they are toxic. In others, they are beneficial. While much is known about phenazine production and the effect of phenazines on producing strains, our ability to predict how phenazines might shape the composition of environmental microbial communities is poorly constrained. In addition, phenazine prevalence in the rhizosphere has been predicted to increase in arid soils as the climate changes, providing an impetus for further study. As a step toward gaining a predictive understanding of phenazine-linked microbial ecology, we document the effects of phenazines on diverse bacteria that were coisolated from a wheat rhizosphere and identify conditions and phenotypes that correlate with how a strain will respond to phenazines.

Gut microbiota of the threatened takahe: biogeographic patterns and conservation implications.

BACKGROUND: The Aotearoa New Zealand takahe (Porphyrio hochstetteri), once thought to be extinct, is a nationally threatened flightless rail under intensive conservation management. While there has been previous research into disease-related microbes in takahe, little is known about the microbes present in the gastrointestinal tract. Given the importance of gut-associated microbes to herbivore nutrition and immunity, knowledge of these communities is likely to be of considerable conservation value. Here we examined the gut microbiotas of 57 takahe at eight separate locations across Aotearoa New Zealand. RESULTS: Faecal samples, taken as a proxy for the hindgut bacterial community, were subjected to 16S rRNA gene amplicon sequencing using Illumina MiSeq. Phylogenetic analysis of > 2200 amplicon sequence variants (ASVs) revealed nine main bacterial phyla (Acidobacteriota, Actinobacteriota, Bacteroidota, Campilobacterota, Firmicutes, Fusobacteriota, Planctomycetota, Proteobacteria, and Verrucomicrobiota) that accounted for the majority of sequence reads. Location was a significant effect (p value < 0.001, 9999 permutations) that accounted for 32% of the observed microbiota variation. One ASV, classified as Lactobacillus aviarius, was present in all samples at an average relative abundance of 17% (SD = 23.20). There was strong evidence (p = 0.002) for a difference in the abundance of the genus Lactobacillus between locations. A common commensal bacterium previously described in takahe, Campylobacter spp., was also detected in most faecal samples. CONCLUSIONS: Location plays a pivotal role in the observed variation among takahe gut bacterial communities and is potentially due to factors such as supplemental feeding and medical treatment experienced by birds housed in captivity at one of the eight sampled sites. These data present a first glimpse of the previously unexplored takahe gut microbiota and provide a baseline for future microbiological studies and conservation efforts.

From the soil to the clinic: the impact of microbial secondary metabolites on antibiotic tolerance and resistance.

Secondary metabolites profoundly affect microbial physiology, metabolism and stress responses. Increasing evidence suggests that these molecules can modulate microbial susceptibility to commonly used antibiotics; however, secondary metabolites are typically excluded from standard antimicrobial susceptibility assays. This may in part account for why infections by diverse opportunistic bacteria that produce secondary metabolites often exhibit discrepancies between clinical antimicrobial susceptibility testing results and clinical treatment outcomes. In this Review, we explore which types of secondary metabolite alter antimicrobial susceptibility, as well as how and why this phenomenon occurs. We discuss examples of molecules that opportunistic and enteric pathogens either generate themselves or are exposed to from their neighbours, and the nuanced impacts these molecules can have on tolerance and resistance to certain antibiotics.

Bacterial defenses against a natural antibiotic promote collateral resilience to clinical antibiotics.

Bacterial opportunistic human pathogens frequently exhibit intrinsic antibiotic tolerance and resistance, resulting in infections that can be nearly impossible to eradicate. We asked whether this recalcitrance could be driven by these organisms' evolutionary history as environmental microbes that engage in chemical warfare. Using Pseudomonas aeruginosa as a model, we demonstrate that the self-produced antibiotic pyocyanin (PYO) activates defenses that confer collateral tolerance specifically to structurally similar synthetic clinical antibiotics. Non-PYO-producing opportunistic pathogens, such as members of the Burkholderia cepacia complex, likewise display elevated antibiotic tolerance when cocultured with PYO-producing strains. Furthermore, by widening the population bottleneck that occurs during antibiotic selection and promoting the establishment of a more diverse range of mutant lineages, PYO increases apparent rates of mutation to antibiotic resistance to a degree that can rival clinically relevant hypermutator strains. Together, these results reveal an overlooked mechanism by which opportunistic pathogens that produce natural toxins can dramatically modulate the efficacy of clinical antibiotics and the evolution of antibiotic resistance, both for themselves and other members of clinically relevant polymicrobial communities.

The transcription factors ActR and SoxR differentially affect the phenazine tolerance of Agrobacterium tumefaciens.

Bacteria in soils encounter redox-active compounds, such as phenazines, that can generate oxidative stress, but the mechanisms by which different species tolerate these compounds are not fully understood. Here, we identify two transcription factors, ActR and SoxR, that play contrasting yet complementary roles in the tolerance of the soil bacterium Agrobacterium tumefaciens to phenazines. We show that ActR promotes phenazine tolerance by proactively driving expression of a more energy-efficient terminal oxidase at the expense of a less efficient alternative, which may affect the rate at which phenazines abstract electrons from the electron transport chain (ETC) and thereby generate reactive oxygen species. SoxR, on the other hand, responds to phenazines by inducing expression of several efflux pumps and redox-related genes, including one of three copies of superoxide dismutase and five novel members of its regulon that could not be computationally predicted. Notably, loss of ActR is far more detrimental than loss of SoxR at low concentrations of phenazines, and also increases dependence on the otherwise functionally redundant SoxR-regulated superoxide dismutase. Our results thus raise the intriguing possibility that the composition of an organism's ETC may be the driving factor in determining sensitivity or tolerance to redox-active compounds.

The Low-Diversity Fecal Microbiota of the Critically Endangered Kakapo Is Robust to Anthropogenic Dietary and Geographic Influences.

The critically endangered kakapo, an herbivorous parrot endemic to New Zealand, is subject to intensive management to increase its population size. Key aspects of the management program include supplementary feeding and translocation of kakapo between different predator-free islands to optimize the genetic composition of the breeding populations. While these practices have helped boost the kakapo population, their impact on the kakapo fecal microbiota is uncertain. Previous studies have found that the kakapo possesses a low-diversity fecal microbiota, typically dominated by Escherichia/Shigella spp. However, the question of whether the low diversity of the kakapo fecal microbiota is an inadvertent consequence of human interventions has yet to be investigated. To that end, we used high-throughput Illumina sequencing of 16S rRNA gene amplicons obtained from fecal material of 63 kakapo representing different diets, islands, and ages. Remarkably, neither supplementary feeding nor geographic location were associated with significant differences in the overall fecal microbial community structures of adult kakapo, suggesting that the kakapo's low-diversity fecal microbiota is both inherent to this species and robust to these external influences.

Nutrient Distribution and Absorption in the Colonial Hydroid Podocoryna carnea Is Sequentially Diffusive and Directional.

The distribution and absorption of ingested protein was characterized within a colony of Podocoryna carnea when a single polyp was fed. Observations were conducted at multiple spatial and temporal scales at three different stages of colony ontogeny with an artificial food item containing Texas Red conjugated albumin. Food pellets were digested and all tracer absorbed by digestive cells within the first 2-3 hours post-feeding. The preponderance of the label was located in the fed polyp and in a transport-induced diffusion pattern surrounding the fed polyp. After 6 hours post-feeding particulates re-appeared in the gastrovascular system and their absorption increased the area over which the nutrients were distributed, albeit still in a pattern that was centered on the fed polyp. At later intervals, tracer became concentrated in some stolon tips, but not in others, despite the proximity of these stolons either to the fed polyp or to adjacent stolons receiving nutrients. Distribution and absorption of nutrients is sequentially diffusive and directional.