Millennium Initiative for Collaborative Research on Bacterial Resistance

OBJECTIVES: In the context of the coronavirus disease 2019 (COVID-19) pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. This study was performed to evaluate a novel rapid antigen detection test (RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory samples. METHODS: The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected COVID-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real-time (RT)-PCR. RESULTS: A total of 127 samples were included; 82 were RT-PCR-positive. The median patient age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (95% confidence interval 86.5-97.4%) and 100% (95% confidence interval 92.1-100%), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. CONCLUSIONS: The RDT evaluated in this study showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health.

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.

BACKGROUND: Several countries have authorised or begun using a booster vaccine dose against COVID-19. Policy makers urgently need evidence of the effectiveness of additional vaccine doses and its clinical spectrum for individuals with complete primary immunisation schedules, particularly in countries where the primary schedule used inactivated SARS-CoV-2 vaccines. METHODS: Using individual-level data, we evaluated a prospective, observational, national-level cohort of individuals (aged ≥16 years) affiliated with the Fondo Nacional de Salud insurance programme in Chile, to assess the effectiveness of CoronaVac (Sinovac Biotech), AZD1222 (Oxford-AstraZeneca), or BNT162b2 (Pfizer-BioNTech) vaccine boosters in individuals who had completed a primary immunisation schedule with CoronaVac, compared with unvaccinated individuals. Individuals administered vaccines from Feb 2, 2021, to the prespecified study end date of Nov 10, 2021, were evaluated; we excluded individuals with a probable or confirmed SARS-CoV-2 infection (RT-PCR or antigen test) on or before Feb 2, 2021, and individuals who had received at least one dose of any COVID-19 vaccine before Feb 2, 2021. We estimated the vaccine effectiveness of booster doses against laboratory-confirmed symptomatic COVID-19 (symptomatic COVID-19) cases and COVID-19 outcomes (hospitalisation, admission to the intensive care unit [ICU], and death We used inverse probability-weighted and stratified survival regression models to estimate hazard ratios, accounting for time-varying vaccination status and adjusting for relevant demographic, socioeconomic, and clinical confounders. We estimated the change in hazard from unvaccinated status to vaccinated status associated with the primary immunisation series and a booster vaccine. FINDINGS: 11 174 257 individuals were eligible for this study, among whom 4 127 546 completed a primary immunisation schedule (two doses) with CoronaVac and received a booster dose during the study period. 1 921 340 (46·5%) participants received an AZD1222 booster, 2 019 260 (48·9%) received a BNT162b2 booster, and 186 946 (4·5%) received a homologous booster with CoronaVac. We calculated an adjusted vaccine effectiveness (weighted stratified Cox model) in preventing symptomatic COVID-19 of 78·8% (95% CI 76·8-80·6) for a three-dose schedule with CoronaVac, 96·5% (96·2-96·7) for a BNT162b2 booster, and 93·2% (92·9-93·6) for an AZD1222 booster. The adjusted vaccine effectiveness against COVID-19-related hospitalisation, ICU admission, and death was 86·3% (83·7-88·5), 92·2% (88·7-94·6), and 86·7% (80·5-91·0) for a homologous CoronaVac booster, 96·1% (95·3-96·9), 96·2% (94·6-97·3), and 96·8% (93·9-98·3) for a BNT162b2 booster, and 97·7% (97·3-98·0), 98·9% (98·5-99·2), and 98·1% (97·3-98·6) for an AZD1222 booster. INTERPRETATION: Our results suggest that a homologous or heterologous booster dose for individuals with a complete primary vaccination schedule with CoronaVac provides a high level of protection against COVID-19, including severe disease and death. Heterologous boosters showed higher vaccine effectiveness than a homologous booster for all outcomes, providing additional support for a mix-and-match approach. FUNDING: Agencia Nacional de Investigación y Desarrollo through the Fondo Nacional de Desarrollo Científico y Tecnológico, Millennium Science Initiative Program, and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias.

We present scientific perspectives on the impact of the COVID-19 pandemic and global food security. International organizations and current evidence based on other respiratory viruses suggests COVID-19 is not a food safety issue, i.e., there is no evidence associating food or food packaging with the transmission of the virus causing COVID-19 (SARS-CoV-2), yet an abundance of precaution for this exposure route seems appropriate. The pandemic, however, has had a dramatic impact on the food system, with direct and indirect consequences on lives and livelihoods of people, plants, and animals. Given the complexity of the system at risk, it is likely that some of these consequences are still to emerge over time. To date, the direct and indirect consequences of the pandemic have been substantial including restrictions on agricultural workers, planting, current and future harvests; shifts in agricultural livelihoods and food availability; food safety; plant and animal health and animal welfare; human nutrition and health; along with changes in public policies. All aspects are crucial to food security that would require "One Health" approaches as the concept may be able to manage risks in a cost-effective way with cross-sectoral, coordinated investments in human, environmental, and animal health. Like climate change, the effects of the COVID-19 pandemic will be most acutely felt by the poorest and most vulnerable countries and communities. Ultimately, to prepare for future outbreaks or threats to food systems, we must take into account the Sustainable Development Goals of the United Nations and a "Planetary Health" perspective.

The prediction of reactivity is one of the long-standing objectives of chemistry, contributing to enforce the link between theory and experiment. In particular, the regioselectivity of aromatic molecules has motivated the proposal of different reactivity descriptors based on foundational theories, like Frontier Molecular Orbital (FMO) theory and density functional theory, to predict and rationalize such regioselectivity. This article examines cases where reactivity descriptors, based on FMO theories, are known to have failed, specifically on electrophilic aromatic substitution reactions, through a simple but effective new reactivity model: the Orbital-weighted Fukui function ( fw-(r)) and its topological analysis. Interestingly, this descriptor proves to be effective in adequately predicting regioselectivities where other approximations failed. © 2017 Wiley Periodicals, Inc.

The angular dependence of the remanence and coercivity of Ni nanowire arrays produced inside the pores of anodic alumina membranes has been studied. By comparing our analytical calculations with our measurements, we conclude that the magnetization reversal in this array is driven by means of the nucleation and propagation of a transverse wall. A simple model based on an adapted Stoner–Wohlfarth model is used to explain the angular dependence of the coercivity.

Atomic layer deposition (ALD) and electrodeposition are combined with a porous template to create ordered arrays of nanowires in which a nickel core and an iron oxide shell are separated by a silica spacer layer. The switching of each magnetic component is distinct and occurs at a field that depends on the tunable thicknesses of the various layers. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND: Early severity estimates of coronavirus disease 2019 (COVID-19) are critically needed to assess the potential impact of the ongoing pandemic in different demographic groups. Here we estimate the real-time delay-adjusted case fatality rate across nine age groups by gender in Chile, the country with the highest testing rate for COVID-19 in Latin America. METHODS: We used a publicly available real-time daily series of age-stratified COVID-19 cases and deaths reported by the Ministry of Health in Chile from the beginning of the epidemic in March through August 31, 2020. We used a robust likelihood function and a delay distribution to estimate real-time delay-adjusted case-fatality risk and estimate model parameters using a Monte Carlo Markov Chain in a Bayesian framework. RESULTS: As of August 31, 2020, our estimates of the time-delay adjusted case fatality rate (CFR) for men and women are 4.16% [95% Credible Interval (CrI): 4.09-4.24%] and 3.26% (95% CrI: 3.19-3.34%), respectively, while the overall estimate is 3.72% (95% CrI: 3.67-3.78%). Seniors aged 80 years and over have an adjusted CFR of 56.82% (95% CrI: 55.25-58.34%) for men and 41.10% (95% CrI: 40.02-42.26%) for women. Results showed a peak in estimated CFR during the June peak of the epidemic. The peak possibly reflects insufficient laboratory capacity, as illustrated by high test positivity rates (33% positive 7-day average nationally in June), which may have resulted in lower reporting rates. CONCLUSIONS: Severity estimates from COVID-19 in Chile suggest that male seniors, especially among those aged ≥ 70 years, are being disproportionately affected by the pandemic, a finding consistent with other regions. The ongoing pandemic is imposing a high death toll in South America, and Chile has one of the highest reported mortality rates globally thus far. These real-time estimates may help inform public health officials' decisions in the region and underscore the need to implement more effective measures to ameliorate fatality.

Antimicrobial resistance (AMR) represents a major threat to human and animal health. Part of the AMR dimension is the circulation of extended-spectrum β-lactamases producing-Escherichia coli (ESBL-E. coli), which is now commonly reported among companion animals. However, the global perspective of the prevalence and population structure of ESBL-E. coli circulating in dogs and cats has not been estimated limiting our understanding of their role in the dissemination of ESBL-E. coli. The aim of this study was to compare the prevalence of ESBL-E. coli between dogs and cats and across countries through meta-analysis. We also performed a scoping review to summarize the current knowledge on ESBL genes and E. coli clones circulating among companion animals. A total of 128 studies published in PubMed, Web of Science, and Scopus up to April 2020 were selected and contained information on prevalence and/or molecular characterization of ESBL genes and ESBL-E. coli clones. Our review shows an increase in the number of publications between 2000 and 2019, concentrated mainly in Europe. Prevalence varied across continents, ranging from 0.63% (Oceania) to 16.56% (Africa) in dogs and from 0% (Oceania) to 16.82% (Asia) in cats. Although there were twice as many studies reporting prevalence on dogs (n = 61) than on cats (n = 32), and only 9 studies focused exclusively on cats, our meta-analysis showed no difference in the global prevalence of ESBL-E. coli between dogs (6.87% [95% CI: 4.46–10.45%]) and cats (5.04% [95% CI: 2.42–10.22%]). A considerable diversity of ESBL genes (n = 60) and sequence types (ST) (n = 171) were recovered from companion animals. ESBL-E. coli encoded by CTX-M-15 (67.5%, 77/114) and SHV-12 (21.9%, 25/114), along with resistant strains of ST38 (22.7%, 15/66) and ST131 (50%, 33/66) were widespread and detected in all continents. While presence of ESBL-E. coli is widespread, the drivers influencing the observed ESBL-E. coli prevalence and the clinical relevance in veterinary medicine and public health along with economic impact of ESBL-E. coli infections among companion animals need to be further investigated.

The outbreak of the B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron) has caused an unprecedented number of Coronavirus Disease 2019 (COVID-19) cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but, to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3-5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of Sinovac's inactivated SARS-CoV-2 vaccine (CoronaVac). We used inverse probability-weighted survival regression models to estimate hazard ratios of symptomatic COVID-19, hospitalization and admission to an intensive care unit (ICU) for children with complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between 6 December 2021 and 26 February 2022, during the Omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95% confidence interval (CI), 36.5-39.9) against symptomatic COVID-19, 64.6% (95% CI, 49.6-75.2) against hospitalization and 69.0% (95% CI, 18.6-88.2) against ICU admission. The effectiveness against symptomatic COVID-19 was modest; however, protection against severe disease was high. These results support vaccination of children aged 3-5 years to prevent severe illness and associated complications and highlight the importance of maintaining layered protections against SARS-CoV-2 infection.

Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host–pathogen interactions.

β-lactam antibiotics, such as penicillin share a very unstable chemical structure. In water-based solutions, such as those used for clinical applications, the β-lactam ring is readily opened due to a nucleophilic or electrophilic attack, leading to the loss of antimicrobial activity. Since the achievement and maintenance of optimum therapeutic levels of β-lactam antibiotics is critical for the resolution of many infectious clinical situations, and to avoid antibiotic resistance generation, the design of new non-aqueous dosage forms is urgent. Recently, natural deep eutectic solvents (NADES) have emerged as alternative non-toxic and non-aqueous solvents for different biomedical applications. In this work, we formulated and characterized a NADES composed by betaine and urea (BU). Using this solvent, we evaluated the stability of clavulanic acid (CLV) and imipenem (IMP) and characterized their antimicrobial activities calculating the minimal inhibitory concentration. Characterization of BU solvent by infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR) indicated that the obtained solvent has a microstructure mainly based on hydrogen bonding interactions and water addition strongly affects its dynamic. The stability of β-lactam antibiotic IMP and CLV using this solvent was increased by 7 fold and 2.5 fold respectively compared to water when analysed seven days after being dissolved. Microbiological assays showed that antibacterial activity at day seven was significantly decreased for both CLV and IMP when dissolved in water, while no change in their antibacterial properties was observed when antibiotics were dissolved in BU. The increased stability of IMP and CLV in BU may be related to the inert behaviour of the solvent and the higher dynamic restriction that helps antibiotics to maintain a more stable conformation. These data suggest the potential use of BU as a solvent to prevent degradation of β-lactam antibiotics.

Based on the one-body particle-antiparticle Dirac theory of electrons, a set of relativistic quantum fluid equations for a spin half plasma is derived. The particle-antiparticle nature of the relativistic particles is explicit in this fluid theory, which also includes quantum effects such as spin. The nonrelativistic limit is shown to be in agreement with previous attempts to develop a spin plasma theory derived from the Pauli Hamiltonian. Harnessing the formalism to the study of electromagnetic mode propagation, conceptually new phenomena are revealed; the particle-antiparticle effects increase the fluid opacity to these waves, while the spin effects tend to make the fluid more transparent.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Anthropic activity in Antarctica has been increasing considerably in recent years, which could have an important impact on the local microbiota affecting multiple features, including the bacterial resistome. As such, our study focused on determining the antibiotic-resistance patterns and antibiotic-resistance genes of bacteria recovered from freshwater samples collected in areas of Antarctica under different degrees of human influence. Aerobic heterotrophic bacteria were subjected to antibiotic susceptibility testing and PCR. The isolates collected from regions of high human intervention were resistant to several antibiotic groups, and were mainly associated with the presence of genes encoding aminoglycosides-modifying enzymes (AMEs) and extended-spectrum β-lactamases (ESBLs). Moreover, these isolates were resistant to synthetic and semi-synthetic drugs, in contrast with those recovered from zones with low human intervention, which resulted highly susceptible to antibiotics. On the other hand, we observed that zone A, under human influence, presented a higher richness and diversity of antibiotic-resistance genes (ARGs) in comparison with zones B and C, which have low human activity. Our results suggest that human activity has an impact on the local microbiota, in which strains recovered from zones under anthropic influence were considerably more resistant than those collected from remote regions.

Bacterial quorum sensing (QS) is a cell-to-cell communication system that governs the expression of a large set of genes involved in bacterial-host interactions, including the production of virulence factors. Conversely, the hosts can produce anti-QS compounds to impair virulence of bacterial pathogens. One of these inhibitors is the plant flavonoid naringenin, which impairs the production of QS-regulated Pseudomonas aeruginosa virulence factors. In the present work, we analyse the molecular basis for such inhibition. Our data indicate that naringenin produces its effect by directly binding the QS regulator LasR, hence competing with its physiological activator, N-(3-oxo-dodecanoyl)-L-homoserine lactone (3OC12-HSL). The in vitro analysis of LasR binding to its cognate target DNA showed that the capacity of naringenin to outcompete 3OC12-HSL, when the latter is previously bound to LasR, is low. By using an E. coli LasR-based biosensor strain, which does not produce 3OC12-HSL, we determined that the inhibition of LasR is more efficient when naringenin binds to nascent LasR than when this regulator is already activated through 3OC12-HSL binding. According to these findings, at early exponential growth phase, when the amount of 3OC12-HSL is low, naringenin should proficiently inhibit the P. aeruginosa QS response, whereas at later stages of growth, once 3OC12-HSL concentration reaches a threshold enough for binding LasR, naringenin would not efficiently inhibit the QS response. To test this hypothesis, we analyse the potential effect of naringenin over the QS response by adding naringenin to P. aeruginosa cultures at either time zero (early inhibition) or at stationary growth phase (late inhibition). In early inhibitory conditions, naringenin inhibited the expression of QS-regulated genes, as well as the production of the QS-regulated virulence factors, pyocyanin and elastase. Nevertheless, in late inhibitory conditions, the P. aeruginosa QS response was not inhibited by naringenin. Therefore, this time-dependent inhibition may compromise the efficiency of this flavonoid, which will be effective just when used against bacterial populations presenting low cellular densities, and highlight the importance of searching for QS inhibitors whose mechanism of action does not depend on the QS status of the population.

BACKGROUND: Governments worldwide have implemented large-scale non-pharmaceutical interventions, such as social distancing or school closures, to prevent and control the growth of the COVID-19 pandemic. These strategies, implemented with varying stringency, have imposed substantial social and economic costs to society. As some countries begin to reopen and ease mobility restrictions, lockdowns in smaller geographic areas are increasingly considered an attractive policy intervention to mitigate societal costs while controlling epidemic growth. Nevertheless, there is a lack of empirical evidence to support these decisions. METHODS: Drawing from a rich data set of localized lockdowns in Chile, we used econometric methods to measure the reduction in local economic activity from lockdowns when applied to smaller or larger geographical areas. We measured economic activity by tax collection at the municipality-level. RESULTS: Our results show that lockdowns were associated with a 10%-15% drop in local economic activity, which is twice the reduction in local economic activity suffered by municipalities that were not under lockdown. A three-to-four-month lockdown had a similar effect on economic activity than a year of the 2009 great recession. We found costs are proportional to the population under lockdown, without differences when lockdowns were measured at the municipality or city-wide levels. CONCLUSIONS: Our findings suggest that localized lockdowns have a large effect on local economic activity, but these effects are proportional to the population under lockdown. Our results suggest that epidemiological criteria should guide decisions about the optimal size of lockdown areas since the proportional impact of lockdowns on the economy seems to be unchanged by scale.

Peru implemented strict social distancing measures during the early phase of the epidemic and is now experiencing one of the largest CoVID-19 epidemics in Latin America. Estimates of disease severity are an essential indicator to inform policy decisions about the intensity and duration of interventions needed to mitigate the outbreak. Here we derive delay-adjusted case fatality risks (aCFR) of CoVID-19 in a middle-income country in South America.We utilize government-reported time series of CoVID-19 cases and deaths in Peru stratified by age group and gender.As of May 25, 2020, we estimate the aCFR for men and women at 10.8% (95%CrI: 10.5-11.1%) and 6.5% (95%CrI: 6.2-6.8%), respectively, whereas the overall aCFR was estimated at 9.1% (95%CrI: 8.9-9.3%). Our results show that senior individuals have been the most severely affected by CoVID-19, particularly men, with an aCFR of nearly 60% for those aged 80- years. We also found that men have a significantly higher cumulative morbidity ratio across most age groups (proportion test, p-value< 0.001), with the exception of those aged 0-9 years.The ongoing CoVID-19 pandemic is generating a substantial mortality burden in Peru. Senior individuals, especially those older than 70 years, are being disproportionately affected by the CoVID-19 pandemic.