A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria

Sulfonamide-degrading bacteria have been discovered in various environments, suggesting the presence of novel resistance mechanisms via drug inactivation. In this study, Microbacterium sp. CJ77 capable of utilizing various sulfonamides as a sole carbon source was isolated from a composting facility. Genome and proteome analyses revealed that a gene cluster containing a flavin-dependent monooxygenase and a flavin reductase was highly up-regulated in response to sulfonamides. Biochemical analysis showed that the two-component monooxygenase system was key enzymes for the initial cleavage of sulfonamides. Co-expression of the two-component system in Escherichia coli conferred decreased susceptibility to sulfamethoxazole, indicating that the genes encoding drug-inactivating enzymes are potential resistance determinants. Comparative genomic analysis revealed that the gene cluster containing sulfonamide monooxygenase (renamed as sulX) and flavin reductase (sulR) was highly conserved in a genomic island shared among sulfonamide-degrading actinobacteria, all of which also contained sul1-carrying class 1 integrons. These results suggest that the sulfonamide metabolism may have evolved in sulfonamide-resistant bacteria which had already acquired the class 1 integron under sulfonamide selection pressures. Furthermore, the presence of multiple insertion sequence elements and putative composite transposon structures containing the sulX gene cluster indicated potential mobilization. This is the first study to report that sulX responsible for both sulfonamide degradation and resistance is prevalent in sulfonamide-degrading actinobacteria and its genetic signatures indicate horizontal gene transfer of the novel resistance gene

Revisiting Polymorphic Diversity of Aminoglycoside N-Acetyltransferase AAC(6′)-Ib Based on Bacterial Genomes of Human, Animal, and Environmental Origins

The prevalence of aac(6′)-Ib variants has been demonstrated in numerous epidemiological studies. We revisited the polymorphic diversity of aminoglycoside 6’-N-acetyltransferase gene [aac(6′)-Ib] in the bacterial genome databases based on One Health perspectives. aac(6′)-Ib was searched against bacterial complete and draft genome databases of NCBI. Based on the major polymorphic residues 102, 117, and 179, taxonomy, ecology, and temporal emergence of bacterial isolates harboring variants of aac(6′)-Ib gene were evaluated using whole-genome sequences available in the databases. A total of 3,964 aac(6′)-Ib sequences were found to be present in the genomes of 34 bacterial genera, mostly found in Gammaproteobacteria. Among these, aac(6′)-Ib-cr variant, known to confer fluoroquinolone resistance, were increasingly detected in bacterial genomes and most abundant in the genera Klebsiella and Escherichia, thereby suggesting that these genera were the major reservoirs of the plasmid-mediated quinolone resistance (PMQR) determinant. The proportions of the cr variant were higher in animal and environmental isolates than in human isolates, among which the variant was dominant (>50%) in the genomes of intestinal, rectal, and fecal origins. In addition, our study suggested that the prevalence of the cr variant was associated with the occurrence of a variant with the mutation L117 (IbL). An integrated surveillance system for antimicrobial resistance in human, animal, and environmental sectors, based on whole-genome sequencing, would provide a better insight into the evolution, ecology, and epidemiology of antimicrobial-resistant bacteria

Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance

BACKGROUND:The impact of human activities on the environmental resistome has been documented in many studies, but there remains the controversial question of whether the increased antibiotic resistance observed in anthropogenically impacted environments is just a result of contamination by resistant fecal microbes or is mediated by indigenous environmental organisms. Here, to determine exactly how anthropogenic influences shape the environmental resistome, we resolved the microbiome, resistome, and mobilome of the planktonic microbial communities along a single river, the Han, which spans a gradient of human activities. RESULTS:The bloom of antibiotic resistance genes (ARGs) was evident in the downstream regions and distinct successional dynamics of the river resistome occurred across the spatial continuum. We identified a number of widespread ARG sequences shared between the river, human gut, and pathogenic bacteria. These human-related ARGs were largely associated with mobile genetic elements rather than particular gut taxa and mainly responsible for anthropogenically driven bloom of the downstream river resistome. Furthermore, both sequence- and phenotype-based analyses revealed environmental relatives of clinically important proteobacteria as major carriers of these ARGs. CONCLUSIONS:Our results demonstrate a more nuanced view of the impact of anthropogenic activities on the river resistome: fecal contamination is present and allows the transmission of ARGs to the environmental resistome, but these mobile genes rather than resistant fecal bacteria proliferate in environmental relatives of their original hosts. Video abstract

Effects of cholesterol levels on outcomes of out-of-hospital cardiac arrest: a cross-sectional study

Objective High cholesterol level is a risk factor for coronary artery disease, and coronary artery disease is a major risk factor for out-of-hospital cardiac arrest (OHCA). However, the effect of cholesterol level on outcomes of OHCA has been poorly studied. This study aimed to determine the effect of cholesterol level on outcomes of OHCA. Methods This cross-sectional study used the CAPTURES (Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance) project database in Korea. Multivariable conditional logistic regression analysis was performed to estimate the effect of cholesterol level on outcomes in OHCA. Results In all, 584 cases of OHCA were analyzed; those with cholesterol levels <120 mg/dL were classified as having low total cholesterol (TC) (n=197), those with levels ranging from 120–199 mg/dL as middle TC (n=322), and those with ≥200 mg/dL as high TC (n=65). Compared to low TC, more patients with middle TC and high TC survived to discharge (9.1% vs. 22.0% and 26.2%, respectively, P=0.001). The good cerebral performance category also increased in that order (4.1 % vs. 14.6% and 23.1%, respectively, P≤0.001). Comparing middle TC and high TC with low TC, adjusted odds ratios (95% confidence intervals) were 1.97 (1.06 to 3.64) and 2.53 (1.08 to 5.92) for survival to discharge, respectively, and 2.53 (1.07 to 5.98) and 4.73 (1.63 to 13.71) for good neurological recovery, respectively. Conclusion Higher cholesterol is associated with better outcomes in OHCA; cholesterol level is a good predictor of outcomes of OHCA

Comparison of trauma systems in Asian countries: a cross-sectional study.

OBJECTIVE: This study aimed to compare the demographic characteristics and trauma service structures and processes of hospitals in 15 countries across the Asia Pacific, and to provide baseline data for the integrated trauma database: the Pan-Asian Trauma Outcomes Study (PATOS). METHODS: Medical directors and emergency physicians at PATOS-participating hospitals in countries across the Asia Pacific were surveyed through a standardized questionnaire. General information, trauma care system data, and trauma emergency department (ED) outcomes at each hospital were collected by email and analyzed using descriptive statistics. RESULTS: Survey data from 35 hospitals across 15 countries were collected from archived data between June 2014 and July 2015. Designated trauma centers were identified as the highest hospital level for trauma patients in 70% of surveyed countries. Half of the hospitals surveyed had special teams for trauma care, and almost all prepared activation protocol documents for these teams. Most hospitals offered specialized trauma education programs, and 72.7% of hospitals had a hospital-based trauma registry. The total number of trauma patients visiting the ED across 25 of the hospitals was 300,376. The overall survival-to-discharge rate was 97.2%; however, it varied greatly between 85.1% and 99.7%. The difference between survival-to-discharge rates of moderate and severe injury groups was highest in Taiwan (41.8%) and lowest in Thailand (18.6%). CONCLUSION: Trauma care systems and ED outcomes vary widely among surveyed hospitals and countries. This information is useful to build further detailed, systematic platforms for trauma surveillance and evidence-based trauma care policies

Impact of sulfamethoxazole on a riverine microbiome

The continued emergence of bacterial pathogens presenting antimicrobial resistance is widely recognised as a global health threat and recent attention focused on potential environmental reservoirs of antibiotic resistance genes (ARGs). Freshwater environments such as rivers represent a potential hotspot for ARGs and antibiotic resistant bacteria as they are receiving systems for effluent discharges from wastewater treatment plants (WWTPs). Effluent also contains low levels of different antimicrobials including antibiotics and biocides. Sulfonamides are antibacterial chemicals widely used in clinical, veterinary and agricultural settings and are frequently detected in sewage sludge and manure in addition to riverine ecosystems. The impact of such exposure on ARG prevalence and diversity is unknown, so the aim of this study was to investigate the release of a sub-lethal concentration of the sulfonamide compound sulfamethoxazole (SMX) on the river bacterial microbiome using a flume system. This system was a semi-natural in vitro flume using river water (30 L) and sediment (6 kg) with circulation to mimic river flow. A combination of ‘omics’ approaches were conducted to study the impact of SMX exposure on the microbiomes within the flumes. Metagenomic analysis showed that the addition of low concentrations of SMX (<4 μg L−1) had a limited effect on the bacterial resistome in the water fraction only, with no impact observed in the sediment. Metaproteomics did not show differences in ARGs expression with SMX exposure in water. Overall, the river bacterial community was resilient to short term exposure to sub-lethal concentrations of SMX which mimics the exposure such communities experience downstream of WWTPs throughout the year

Comparison of trauma systems in Asian countries: a cross-sectional study

Objective This study aimed to compare the demographic characteristics and trauma service structures and processes of hospitals in 15 countries across the Asia Pacific, and to provide baseline data for the integrated trauma database: the Pan-Asian Trauma Outcomes Study (PATOS). Methods Medical directors and emergency physicians at PATOS-participating hospitals in countries across the Asia Pacific were surveyed through a standardized questionnaire. General information, trauma care system data, and trauma emergency department (ED) outcomes at each hospital were collected by email and analyzed using descriptive statistics. Results Survey data from 35 hospitals across 15 countries were collected from archived data between June 2014 and July 2015. Designated trauma centers were identified as the highest hospital level for trauma patients in 70% of surveyed countries. Half of the hospitals surveyed had special teams for trauma care, and almost all prepared activation protocol documents for these teams. Most hospitals offered specialized trauma education programs, and 72.7% of hospitals had a hospital-based trauma registry. The total number of trauma patients visiting the ED across 25 of the hospitals was 300,376. The overall survival-to-discharge rate was 97.2%; however, it varied greatly between 85.1% and 99.7%. The difference between survival-to-discharge rates of moderate and severe injury groups was highest in Taiwan (41.8%) and lowest in Thailand (18.6%). Conclusion Trauma care systems and ED outcomes vary widely among surveyed hospitals and countries. This information is useful to build further detailed, systematic platforms for trauma surveillance and evidence-based trauma care policies