Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases

The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours

Varieties of living things: Life at the intersection of lineage and metabolism

publication-status: Publishedtypes: Articl

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

High-Throughput Screen for Identifying Small Molecules That Target Fungal Zinc Homeostasis

Resistance to traditional antifungal drugs has increased significantly over the past three decades, making identification of novel antifungal agents and new targets an emerging priority. Based on the extraordinary zinc requirement of several fungal pathogens and their well-established sensitivity to zinc deprivation, we developed an efficient cell-based screen to identify new antifungal drugs that target the zinc homeostasis machinery. The screen is based on the zinc-regulated transcription factor Zap1 of Saccharomyces cerevisiae, which regulates transcription of genes like the high-affinity zinc transporter ZRT1. We generated a genetically modified strain of S. cerevisae that reports intracellular zinc deficiency by placing the coding sequence of green fluorescent protein (GFP) under the control of the Zap1-regulated ZRT1 promoter. After showing that the GFP fluorescence signal correlates with low intracellular zinc concentrations in this strain, a protocol was developed for screening small-molecule libraries for compounds that induce Zap1-dependent GFP expression. Comparison of control compounds and known modulators of metal metabolism from the library reveals a robust screen (Z′ = 0.74) and validates this approach to the discovery of new classes of antifungal compounds that interfere with the intracellular zinc homeostasis. Given that growth of many pathogenic organisms is significantly impaired by zinc limitation; these results identify new types of antifungal drugs that target critical nutrient acquisition pathways

Determinants of seasonal influenza vaccination in pregnant women in Valencia, Spain

Background: In most countries the coverage of seasonal influenza vaccination in pregnant women is low. We investigated the acceptance, reasons for rejection and professional involvement related to vaccine information in pregnant women in Valencia, Spain. Methods: Observational retrospective study in 200 pregnant women, 100 vaccinated and 100 unvaccinated, were interviewed during the 2014/2015 vaccination campaign. Electronic medical records, immunization registry and telephone interviews were used to determine reasons for vaccination and immunization rejection. Results: 40.5% of pregnant women in the health department were vaccinated. The midwife was identified as source of information for 89% of women. The vaccine was rejected due to low perceptions of risk of influenza infection (23%), lack of information (19%), considering the vaccine as superfluous (16%), close proximity of delivery date (13%) and fear of side effects (12%). Conclusion: Pregnant women in Spain declined to be vaccinated due to under-estimation of the risk of contracting or being harmed by influenza, and lack of information. Interventions aiming to optimize vaccination coverage should include information addressing the safety and effectiveness of the current vaccine together with improved professional training and motivation

Using a summary measure for multiple quality indicators in primary care: the Summary QUality InDex (SQUID)

BACKGROUND: Assessing the quality of primary care is becoming a priority in national healthcare agendas. Audit and feedback on healthcare quality performance indicators can help improve the quality of care provided. In some instances, fewer numbers of more comprehensive indicators may be preferable. This paper describes the use of the Summary Quality Index (SQUID) in tracking quality of care among patients and primary care practices that use an electronic medical record (EMR). All practices are part of the Practice Partner Research Network, representing over 100 ambulatory care practices throughout the United States. METHODS: The SQUID is comprised of 36 process and outcome measures, all of which are obtained from the EMR. This paper describes algorithms for the SQUID calculations, various statistical properties, and use of the SQUID within the context of a multi-practice quality improvement (QI) project. RESULTS: At any given time point, the patient-level SQUID reflects the proportion of recommended care received, while the practice-level SQUID reflects the average proportion of recommended care received by that practice's patients. Using quarterly reports, practice- and patient-level SQUIDs are provided routinely to practices within the network. The SQUID is responsive, exhibiting highly significant (p < 0.0001) increases during a major QI initiative, and its internal consistency is excellent (Cronbach's alpha = 0.93). Feedback from physicians has been extremely positive, providing a high degree of face validity. CONCLUSION: The SQUID algorithm is feasible and straightforward, and provides a useful QI tool. Its statistical properties and clear interpretation make it appealing to providers, health plans, and researchers

Antibacterial activity of traditional medicinal plants used by Haudenosaunee peoples of New York State

<p>Abstract</p> <p>Background</p> <p>The evolution and spread of antibiotic resistance, as well as the evolution of new strains of disease causing agents, is of great concern to the global health community. Our ability to effectively treat disease is dependent on the development of new pharmaceuticals, and one potential source of novel drugs is traditional medicine. This study explores the antibacterial properties of plants used in Haudenosaunee traditional medicine. We tested the hypothesis that extracts from Haudenosaunee medicinal plants used to treat symptoms often caused by bacterial infection would show antibacterial properties in laboratory assays, and that these extracts would be more effective against moderately virulent bacteria than less virulent bacteria.</p> <p>Methods</p> <p>After identification and harvesting, a total of 57 different aqueous extractions were made from 15 plant species. Nine plant species were used in Haudenosaunee medicines and six plant species, of which three are native to the region and three are introduced, were not used in traditional medicine. Antibacterial activity against mostly avirulent (<it>Escherichia coli, Streptococcus lactis</it>) and moderately virulent (<it>Salmonella typhimurium, Staphylococcus aureus</it>) microbes was inferred through replicate disc diffusion assays; and observed and statistically predicted MIC values were determined through replicate serial dilution assays.</p> <p>Results</p> <p>Although there was not complete concordance between the traditional use of Haudenosaunee medicinal plants and antibacterial activity, our data support the hypothesis that the selection and use of these plants to treat disease was not random. In particular, four plant species exhibited antimicrobial properties as expected (<it>Achillea millefolium, Ipomoea pandurata, Hieracium pilosella</it>, and <it>Solidago canadensis</it>), with particularly strong effectiveness against <it>S. typhimurium</it>. In addition, extractions from two of the introduced species (<it>Hesperis matronalis </it>and <it>Rosa multiflora</it>) were effective against this pathogen.</p> <p>Conclusions</p> <p>Our data suggest that further screening of plants used in traditional Haudenosaunee medicine is warranted, and we put forward several species for further investigation of activity against <it>S. typhimurium </it>(<it>A. millefolium, H. matronalis, I. pandurata, H. pilosella, R. multiflora, S. canadensis</it>).</p

Potassium and Sodium Transport in Yeast

[EN] As the proper maintenance of intracellular potassium and sodium concentrations is vital for cell growth, all living organisms have developed a cohort of strategies to maintain proper monovalent cation homeostasis. In the model yeast Saccharomyces cerevisiae, potassium is accumulated to relatively high concentrations and is required for many aspects of cellular function, whereas high intracellular sodium/potassium ratios are detrimental to cell growth and survival. The fact that S. cerevisiae cells can grow in the presence of a broad range of concentrations of external potassium (10 M–2.5 M) and sodium (up to 1.5 M) indicates the existence of robust mechanisms that have evolved to maintain intracellular concentrations of these cations within appropriate limits. In this review, current knowledge regarding potassium and sodium transporters and their regulation will be summarized. 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