Birds, with their broad geographic ranges and close association with humans, have historically played an important role as carriers of human disease and as reservoirs for drug-resistant bacteria. ...Here, we examine scientific literature over a 15-year timespan to identify reported avian-bacterial associations and factors that may impact zoonotic disease emergence by classifying traits of bird species and their bacteria. We find that the majority of wild birds studied were migratory, in temperate habitats, and in the order Passeriformes. The highest diversity of bacteria was found on birds in natural habitats. The most frequently reported bacteria were
Escherichia coli
,
Salmonella enterica,
and
Campylobacter jejuni
. Of the bacteria species reported, 54% have shown pathogenicity toward humans. Percentage-wise, more pathogens were found in tropical (vs. temperate) habitats and natural (vs. suburban, urban, or agricultural) habitats. Yet, only 22% were tested for antibiotic resistance, and of those tested, 75% of bacteria species were resistant to at least one antibiotic. There were no significant patterns of antibiotic resistance in migratory versus non-migratory birds, temperate versus tropical areas, or different habitats. We discuss biases in detection and representation, and suggest a need for increased sampling in non-temperate zones and in a wider range of avian species.
During corticogenesis, cells from the medial ganglionic eminence (MGE) migrate tangentially into the neocortical anlage. Here we report that γ-aminobutyric acid (GABA), via GABAA receptors, regulates ...tangential migration. In embryonic telencephalic slices, bicuculline produced an outward current in migrating MGE-derived cells in the neocortex, suggesting the presence of and tonic activation by ambient GABA. Ambient GABA was also present in the MGE, although this required demonstration using as bioassay HEK293 cells expressing high-affinity α6/β2/γ2s recombinant GABAA receptors. The concentration of ambient GABA was 0.5 ± 0.1 μM in both regions. MGE-derived cells before the corticostriate juncture (CSJ) were less responsive to GABA than those in the neocortex, and profiling of GABAA receptor subunit transcripts revealed different expression patterns in the MGE vis-à-vis the neocortex. These findings suggest a dynamic expression of GABAA receptor number or isoform as MGE-derived cells enter the neocortex and become tonically influenced by ambient GABA. Treatment with bicuculline or antibody against GABA did not affect migration of MGE-derived cells before the CSJ but decreased “crossing index,” reflecting impeded migration past the CSJ into the neocortex. Treatment with diazepam or addition of exogenous GABA increased crossing index. We conclude that ambient GABA promotes cortical entry of tangentially migrating MGE-derived cells.
In drug-drug interactions, there are surprising cases in which the growth inhibition of bacteria by a single antibiotic decreases when a second antibiotic is added. These interactions are termed ...suppressive and have been argued to have the potential to limit the evolution of resistance. Nevertheless, little attention has been given to suppressive interactions because clinical studies typically search for increases in killing efficiency and because suppressive interactions are believed to be rare based on pairwise studies.
Here, we quantify the effects of single-, double-, and triple-drug combinations from a set of 14 antibiotics and 3 bacteria strains, totaling 364 unique three-drug combinations per bacteria strain. We find that increasing the number of drugs can increase the prevalence of suppressive interactions: 17% of three-drug combinations are suppressive compared to 5% of two-drug combinations in this study. Most cases of suppression we find (97%) are "hidden" cases for which the triple-drug bacterial growth is less than the single-drug treatments but exceeds that of a pairwise combination.
We find a surprising number of suppressive interactions in higher-order drug combinations. Without examining lower-order (pairwise) bacterial growth, emergent suppressive effects would be missed, potentially affecting our understanding of evolution of resistance and treatment strategies for resistant pathogens. These findings suggest that careful examination of the full factorial of drug combinations is needed to uncover suppressive interactions in higher-order combinations.
Bacteria have evolved diverse mechanisms to survive environments with antibiotics. Temperature is both a key factor that affects the survival of bacteria in the presence of antibiotics and an ...environmental trait that is drastically increasing due to climate change. Therefore, it is timely and important to understand links between temperature changes and selection of antibiotic resistance. This review examines these links by synthesizing results from laboratories, hospitals, and environmental studies. First, we describe the transient physiological responses to temperature that alter cellular behavior and lead to antibiotic tolerance and persistence. Second, we focus on the link between thermal stress and the evolution and maintenance of antibiotic resistance mutations. Finally, we explore how local and global changes in temperature are associated with increases in antibiotic resistance and its spread. We suggest that a multidisciplinary, multiscale approach is critical to fully understand how temperature changes are contributing to the antibiotic crisis.
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Global Change; Microbiology
Novel selection pressures in new environments arise through two distinct processes. First, environmental conditions directly affect the fitness of different phenotypes. Second, phenotypic plasticity ...alters the distribution of phenotypes, thereby placing populations in new selective regimes. A small isolated population of dark‐eyed juncosJunco hyemalisbecame established in San Diego, probably in the early 1980s and probably from the nearby mountains. The relatively mild coastal climate has resulted in an increase in both the mean and the variance of the length of time females breed each year, and this is assumed to be a result of phenotypic plasticity. The population has evolved reduced white in the tail. We studied contemporary patterns of selection on tail white, in the context of the altered breeding season length. Late‐hatched nestlings had higher survival and were in better condition than early‐hatched nestlings, but among survivors, late‐hatched birds had less tail white. We suggest this reflects juvenile mortality favoring individuals with less tail white. In adults, we found weak sexual selection and no viability selection but positive selection on female tail white in association with fecundity. We argue that altered breeding season length had a major impact on patterns of selection and evolution in this population.
Degradation of acoustic signals during transmission presents a challenging selection pressure for animals dependent on vocal communication. Sound transmission properties differ among habitats and may ...drive the evolution of vocal signals in different directions. Urban habitat is expanding worldwide and an increasing number of species, including many birds, must now communicate around buildings and over concrete. Urban habitats are evolutionarily new, although to some extent they may acoustically resemble rocky habitat such as cliffs and canyons. Neither urban nor these natural habitats have been studied in any detail for the selection pressure they may exert on animal communication. Dark-eyed Juncos (Junco hyemalis) commonly inhabit montane pine forests across North America, but for about 25 years an isolated population has been successfully breeding in an urban environment in southern California. We investigated potentially divergent selection pressures on junco songs, using sound transmission experiments with artificial sound stimuli, in natural forest habitat and in this urban habitat. Transmission properties differed significantly, resulting in tails of reflected sound with gradually declining amplitude in the forest and in multiple discrete echoes in the urban environment. We expected environmental selection in urban habitat to favor shorter songs with higher frequencies and slower trill rates. Despite the presence of relatively short urban songs, there was no significant shortening overall. There were also no differences in trill rates, but we did find a significantly higher minimum frequency in the urban junco population compared to three of four forest populations. Although the pattern of song divergence was not consistent and it is difficult to draw firm conclusions from this single urban population, our transmission results suggest that echoes could be important in shaping urban birdsong.
Understanding how multiple stressors interact is needed to predict the dynamical outcomes of diverse biological systems, ranging from drug-resistant pathogens that are combated and treated with ...combination drug therapies to ecosystems impacted by environmental toxicants or disturbances. Nevertheless, extensive studies of higher-order (more than two component) interactions have been lacking. Here, we conduct experiments using 20 three-drug combinations and their effects on the bacterial growth of Escherichia coli. We report our measurements of growth rates in single, pairwise and triple-drug combinations. To uncover emergent interactions, we derive a simple framework to calculate expectations for three-way interactions based on the measured impact of each individual stressor and of each pairwise interaction. Using our framework, we find that (i) emergent antagonisms are more common than emergent synergies and (ii) emergent antagonisms are more common and emergent synergies are more rare than would be inferred from measures of net effects that do not disentangle pairwise interactions from three-way interactions.
Urbanization affects the ecology of wildlife diseases and although it has been suggested that there are lower risks of infection in urban areas, there have been no experiments to support this ...conclusion. We assessed haemosporidian prevalence and intensity in House Sparrows Passer domesticus using field and experimental data under contrasting conditions (i.e. urban vs. non‐urban). For experimental data, we kept 32 male House Sparrows in captivity as a proxy of stress, and for field data we sampled 49 House Sparrows (17 females). We made use of microscopy to determine the relative intensity and used the polymerase chain reaction to estimate infection prevalence. We obtained total leucocyte counts, leucocyte differentials, heterophil/lymphocyte ratio (H/L) as a measure of stress, and the Polychromatic Index as a measure of physiological condition (erythropoiesis). We identified a total of 10 haemosporidian lineages. For field samples (both males and females), we found a significantly higher prevalence of infection in non‐urban House Sparrows than in urban ones. Under experimental conditions, non‐urban House Sparrows showed a higher prevalence than urban ones both before and after captivity, with a significant increase in parasite intensity. The number of infected birds increased after captivity for both urban (~ 32%) and non‐urban House Sparrows (~ 19%), indicating either a recrudescence of chronic and relapses of latent infections or the appearance of infections that had been acquired earlier. The H/L ratio was significantly higher for non‐urban than for urban male House Sparrows before captivity. No difference in H/L was found for urban House Sparrows before and after captivity, indicating tolerance to city stressors. Our results showed a significant decrease in H/L for non‐urban birds after captivity, suggesting higher stress in the non‐urban agricultural environment. Haemosporidian infections were not associated with the H/L ratio. Our study provides evidence that highly urbanized areas within cities represent lower haemosporidian infection risks than do non‐urban areas for House Sparrows.
Temperature variation-through time and across climatic gradients-affects individuals, populations, and communities. Yet how the thermal response of biological systems is altered by environmental ...stressors is poorly understood. Here, we quantify two key features-optimal temperature and temperature breadth-to investigate how temperature responses vary in the presence of antibiotics. We use high-throughput screening to measure growth of Escherichia coli under single and pairwise combinations of 12 antibiotics across seven temperatures that range from 22°C to 46°C. We find that antibiotic stress often results in considerable changes in the optimal temperature for growth and a narrower temperature breadth. The direction of the optimal temperature shifts can be explained by the similarities between antibiotic-induced and temperature-induced damage to the physiology of the bacterium. We also find that the effects of pairs of stressors in the temperature response can often be explained by just one antibiotic out of the pair. Our study has implications for a general understanding of how ecological systems adapt and evolve to environmental changes.
The growth of living organisms varies with temperature. This dependence is described by a temperature response curve that is described by an optimal temperature where growth is maximized and a temperature range (termed breadth) across which the organism can grow. Because an organism's temperature response evolves or acclimates to its environment, it is often assumed to change over only evolutionary or developmental timescales. Counter to this, we show here that antibiotics can quickly (over hours) change the optimal growth temperature and temperature breadth for the bacterium Escherichia coli. Moreover, our results suggest a shared-damage hypothesis: when an antibiotic damages similar cellular components as hot (or cold) temperatures do, this shared damage will combine and compound to more greatly reduce growth when that antibiotic is administered at hot (or cold) temperatures. This hypothesis could potentially also explain how temperature responses are modified by stressors other than antibiotics.
Antibiotics select for resistant bacteria whose existence and emergence is more likely in populations with high phenotypic and genetic diversity. Identifying the mechanisms that generate this ...diversity can thus have clinical consequences for drug-resistant pathogens. We show here that intermediate levels of antibiotics are associated with higher levels of phenotypic diversity in size of colony forming units (cfus), within a single bacterial population. We examine experimentally thousands of populations of bacteria subjected to different disturbance levels that are created by varying antibiotic concentrations. Based on colony sizes, we find that intermediate levels of antibiotics always result in the highest phenotypic variation of this trait. This result is supported across bacterial densities and in the presence of three different antibiotics with two different mechanisms of action. Our results suggest intermediate levels of a stressor (as opposed to very low or very high levels) could affect the phenotypic diversity of a population, at least with regards to the single trait measured here. While this study is limited to a single phenotypic trait within a single species, the results suggest examining phenotypic and genetic variation created by disturbances and stressors could be a promising way to understand and limit variation in pathogens.
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