Systemic inflammation indicators and risk of incident arrhythmias in 478,524 individuals: evidence from the UK Biobank cohort.

BACKGROUND: The role of systemic inflammation in promoting cardiovascular diseases has attracted attention, but its correlation with various arrhythmias remains to be clarified. We aimed to comprehensively assess the association between various indicators of systemic inflammation and atrial fibrillation/flutter (AF), ventricular arrhythmia (VA), and bradyarrhythmia in the UK Biobank cohort. METHODS: After excluding ineligible participants, a total of 478,524 eligible individuals (46.75% male, aged 40-69 years) were enrolled in the study to assess the association between systemic inflammatory indicators and each type of arrhythmia. RESULTS: After covariates were fully adjusted, CRP levels were found to have an essentially linear positive correlation with the risk of various arrhythmias; neutrophil count, monocyte count, and NLR showed a non-linear positive correlation; and lymphocyte count, SII, PLR, and LMR showed a U-shaped association. VA showed the strongest association with systemic inflammation indicators, and it was followed sequentially by AF and bradyarrhythmia. CONCLUSIONS: Multiple systemic inflammatory indicators showed strong associations with the onset of AF, VA, and bradyarrhythmia, of which the latter two have been rarely studied. Active systemic inflammation management might have favorable effects in reducing the arrhythmia burden and further randomized controlled studies are needed.

Chitinase-Like Protein Ym2 (Chil4) Regulates Regeneration of the Olfactory Epithelium via Interaction with Inflammation.

The adult olfactory epithelium (OE) regenerates sensory neurons and nonsensory supporting cells from resident stem cells after injury. How supporting cells contribute to OE regeneration remains largely unknown. In this study, we elucidated a novel role of Ym2 (also known as Chil4 or Chi3l4), a chitinase-like protein expressed in supporting cells, in regulating regeneration of the injured OE in vivo in both male and female mice and cell proliferation/differentiation in OE colonies in vitro We found that Ym2 expression was enhanced in supporting cells after OE injury. Genetic knockdown of Ym2 in supporting cells attenuated recovery of the injured OE, while Ym2 overexpression by lentiviral infection accelerated OE regeneration. Similarly, Ym2 bidirectionally regulated cell proliferation and differentiation in OE colonies. Furthermore, anti-inflammatory treatment reduced Ym2 expression and delayed OE regeneration in vivo and cell proliferation/differentiation in vitro, which were counteracted by Ym2 overexpression. Collectively, this study revealed a novel role of Ym2 in OE regeneration and cell proliferation/differentiation of OE colonies via interaction with inflammatory responses, providing new clues to the function of supporting cells in these processes.SIGNIFICANCE STATEMENT The mammalian olfactory epithelium (OE) is a unique neural tissue that regenerates sensory neurons and nonsensory supporting cells throughout life and postinjury. How supporting cells contribute to this process is not entirely understood. Here we report that OE injury causes upregulation of a chitinase-like protein, Ym2, in supporting cells, which facilitates OE regeneration. Moreover, anti-inflammatory treatment reduces Ym2 expression and delays OE regeneration, which are counteracted by Ym2 overexpression. This study reveals an important role of supporting cells in OE regeneration and provides a critical link between Ym2 and inflammation in this process.

Global magnitude and long-term trend of ischemic heart disease burden attributed to household air pollution from solid fuels in 204 countries and territories, 1990-2019.

Understanding the spatiotemporal variation in the household air pollution from solid fuels (HAP)-related ischemic heart disease (IHD) burden on a global scale from 1990 to 2019 is essential to reduce IHD burden, as well as control HAP exposure. Based on the Global Burden of Disease Study 2019, the numbers and age-standardized rates of IHD mortality and disability-adjusted life years (DALYs) (ASMR and ASDR) attributed to HAP were analyzed by sex and age at global, regional, and national levels. The estimated annual percentage change was calculated to evaluate the temporal trend in burden rates. In 2019, IHD attributed to HAP resulted in 511 170 deaths and 13.18 million DALYs globally. The corresponding ASMR and ASDR were higher in males, increased with age peaking at about 80-94 years, and varied greatly across the world. Despite a remarkable decline in HAP-related IHD was achieved across the world over the past decades, an undesirable increase could be observed in some low-income but with high-burden countries. Sustained and comprehensive efforts are needed to control HAP and reduce the IHD burden, especially in countries and territories with a heavy or increasing burden, such as the Solomon Islands, Vanuatu, Afghanistan, Philippines, Zimbabwe, Lesotho, and Somalia.

Genomic Diversity, Antimicrobial Resistance, and Virulence Gene Profiles of Salmonella Serovar Kentucky Isolated from Humans, Food, and Animal Ceca Content Sources in the United States.

Salmonella serovar Kentucky is frequently isolated from chickens and dairy cattle, but recovery from humans is comparatively low based on the U.S. National Antimicrobial Resistance Monitoring System (NARMS) reports. We aimed to better describe the genetic diversity, antimicrobial resistance, and virulence determinants of Salmonella Kentucky isolates from humans, food animal ceca, retail meat and poultry products, imported foods and food products, and other samples. We analyzed the genomes of 774 Salmonella Kentucky isolates and found that 63% (54/86) of human isolates were sequence type (ST)198, 33% (29/86) were ST152, and 3.5% (3/86) were ST314. Ninety-one percent (570/629) of cecal isolates and retail meat and poultry isolates were ST152 or ST152-like (one allele difference), and 9.2% (58/629) were ST198. Isolates from imported food were mostly ST198 (60%, 22/37) and ST314 (29.7%, 11/37). ST198 isolates clustered into two main lineages. Clade ST198.2 comprised almost entirely isolates from humans and imported foods, all containing triple mutations in the quinolone resistance-determining region (QRDR) that confer resistance to fluoroquinolones. Clade ST198.1 contained isolates from humans, ceca, retail meat and poultry products, and imported foods that largely lacked QRDR mutations. ST152 isolates from cattle had a lineage (Clade 2) distinct from ST152 isolates from chicken (Clade 4), and half of ST152 human isolates clustered within two other clades (Clades 1 and 3), largely distinct from Clades 2 and 4. Although clinical illness associated with Salmonella Kentucky is low, ST198 appears to account for most human infections in the Unites States but is uncommon among ceca of domestic food animals and retail meat and poultry products. These findings, combined with human exposure data, suggest that fluoroquinolone-resistant ST198 infections may be linked to the consumption of food products that are imported or consumed while traveling. We also found unique differences in the composition of virulence genes and antimicrobial resistance genes among the clades, which may provide clues to the host specificity and pathogenicity of Salmonella Kentucky lineages.

Rapid migration of mainland China's coastal erosion vulnerability due to anthropogenic changes.

With the global rise in sea levels caused by climate change and frequent extreme weather processes, high-density population aggregation and human development activities to enhance coastal areas vulnerability, populations, resources, and the ecological environment are facing huge pressure. Natural coastlines are being destroyed, and increasingly serious problems, such as coastal erosion and ecological fragility, have become disasters in coastal zones. The coastal vulnerability changed by climatic variables has created a major concern at regional, national and global scales. By comparing the data of two periods in the past 40 years, coastline vulnerability of coastal erosion in mainland China were evaluated by use of reverse cloud model and AHP with 10 indicators, including natural, anthropogenic, social and economic factors, etc. The main factors controlling coastal erosion included the proportion of Quaternary strata, the gradual reclamation of marine areas as land areas (in kilometres) and the percentage decrease in coastal sediment entering the sea. The secondary impact factors included the high proportion of artificial coastlines and the impacts of waves and storm surges under the influence of relative sea level changes. Human activities could further influence coastal vulnerability, making the erosion risk a considerable concern. Legislation, coordinated management system and technology are proposed to improve the quality of the marine ecological environment.

Purification and Structural Characterization of Dendrobium officinale Polysaccharides and Its Activities.

In this study, Dendrobium officinale polysaccharide (named DOPS-1) was isolated from the stems of Dendrobium officinale by hot-water extraction and purified by using Sephadex G-150 column chromatography. The structural characterization, antioxidant and cytotoxic activity were carried out. Based on the results of HPLC, GC, Congo red experiment, together with periodate oxidation, Smith degradation, SEM, FT-IR, and NMR spectral analysis, it expressed that DOPS-1 was largely composed of mannose, glucose and galacturonic acid in a molar ratio of 3.2 : 1.3 : 1. The molecular weight of DOPS-1 was 1530 kDa and the main chain was composed of (1→4)-ß-D-Glcp, (1→4)-ß-D-Manp and 2-O-acetyl-(1→4)-ß-D-Manp. The measurement results of antioxidant activity showed that DOPS-1 had the strong scavenging activities on hydroxyl radicals, DPPH radicals and superoxide radicals and the high reducing ability in vitro. Moreover, DOPS-1 was cytotoxic to all three human cancer cells of MDA-MB-231, A549 and HepG2.

Identification of a Novel Plasmid-Borne Gentamicin Resistance Gene in Nontyphoidal Salmonella Isolated from Retail Turkey.

The spread of antibiotic-resistant bacteria presents a global health challenge. Efficient surveillance of bacteria harboring antibiotic resistance genes (ARGs) is a critical aspect to controlling the spread. Increased access to microbial genomic data from many diverse populations informs this surveillance but only when functional ARGs are identifiable within the data set. Current, homology-based approaches are effective at identifying the majority of ARGs within given clinical and nonclinical data sets for several pathogens, yet there are still some whose identities remain elusive. By coupling phenotypic profiling with genotypic data, these unknown ARGs can be identified to strengthen homology-based searches. To prove the efficacy and feasibility of this approach, a published data set from the U.S. National Antimicrobial Resistance Monitoring System (NARMS), for which the phenotypic and genotypic data of 640 Salmonella isolates are available, was subjected to this analysis. Six isolates recovered from the NARMS retail meat program between 2011 and 2013 were identified previously as phenotypically resistant to gentamicin but contained no known gentamicin resistance gene. Using the phenotypic and genotypic data, a comparative genomics approach was employed to identify the gene responsible for the observed resistance in all six of the isolates. This gene, grdA, is harbored on a 9,016-bp plasmid that is transferrable to Escherichia coli, confers gentamicin resistance to E. coli, and has never before been reported to confer gentamicin resistance. Bioinformatic analysis of the encoded protein suggests an ATP binding motif. This work demonstrates the advantages associated with coupling genomics technologies with phenotypic data for novel ARG identification.

The mcr-9 Gene of Salmonella and Escherichia coli Is Not Associated with Colistin Resistance in the United States.

Reports of transmissible colistin resistance show the importance of comprehensive colistin resistance surveillance. Recently, a new allele of the mobile colistin resistance (mcr) gene family designated mcr-9, which shows variation in genetic context and colistin susceptibility, was reported. We tested over 100 Salmonella enterica and Escherichia coli isolates with mcr-9 from the National Antimicrobial Resistance Monitoring System (NARMS) in the United States for their susceptibility to colistin and found that every isolate was susceptible, with an MIC of ≤1 µg/ml. Long-read sequencing of 12 isolates revealed mcr-9 on IncHI plasmids that were either independent or integrated into the chromosome. Overall, these results demonstrate that caution is necessary when determining the clinical relevance of new resistance genes.

Zoonotic Source Attribution of Salmonella enterica Serotype Typhimurium Using Genomic Surveillance Data, United States.

Increasingly, routine surveillance and monitoring of foodborne pathogens using whole-genome sequencing is creating opportunities to study foodborne illness epidemiology beyond routine outbreak investigations and case-control studies. Using a global phylogeny of Salmonella enterica serotype Typhimurium, we found that major livestock sources of the pathogen in the United States can be predicted through whole-genome sequencing data. Relatively steady rates of sequence divergence in livestock lineages enabled the inference of their recent origins. Elevated accumulation of lineage-specific pseudogenes after divergence from generalist populations and possible metabolic acclimation in a representative swine isolate indicates possible emergence of host adaptation. We developed and retrospectively applied a machine learning Random Forest classifier for genomic source prediction of Salmonella Typhimurium that correctly attributed 7 of 8 major zoonotic outbreaks in the United States during 1998-2013. We further identified 50 key genetic features that were sufficient for robust livestock source prediction.

Validating the AMRFinder Tool and Resistance Gene Database by Using Antimicrobial Resistance Genotype-Phenotype Correlations in a Collection of Isolates.

Antimicrobial resistance (AMR) is a major public health problem that requires publicly available tools for rapid analysis. To identify AMR genes in whole-genome sequences, the National Center for Biotechnology Information (NCBI) has produced AMRFinder, a tool that identifies AMR genes using a high-quality curated AMR gene reference database. The Bacterial Antimicrobial Resistance Reference Gene Database consists of up-to-date gene nomenclature, a set of hidden Markov models (HMMs), and a curated protein family hierarchy. Currently, it contains 4,579 antimicrobial resistance proteins and more than 560 HMMs. Here, we describe AMRFinder and its associated database. To assess the predictive ability of AMRFinder, we measured the consistency between predicted AMR genotypes from AMRFinder and resistance phenotypes of 6,242 isolates from the National Antimicrobial Resistance Monitoring System (NARMS). This included 5,425 Salmonella enterica, 770 Campylobacter spp., and 47 Escherichia coli isolates phenotypically tested against various antimicrobial agents. Of 87,679 susceptibility tests performed, 98.4% were consistent with predictions. To assess the accuracy of AMRFinder, we compared its gene symbol output with that of a 2017 version of ResFinder, another publicly available resistance gene detection system. Most gene calls were identical, but there were 1,229 gene symbol differences (8.8%) between them, with differences due to both algorithmic differences and database composition. AMRFinder missed 16 loci that ResFinder found, while ResFinder missed 216 loci that AMRFinder identified. Based on these results, AMRFinder appears to be a highly accurate AMR gene detection system.

Using Machine Learning To Predict Antimicrobial MICs and Associated Genomic Features for Nontyphoidal Salmonella.

Nontyphoidal Salmonella species are the leading bacterial cause of foodborne disease in the United States. Whole-genome sequences and paired antimicrobial susceptibility data are available for Salmonella strains because of surveillance efforts from public health agencies. In this study, a collection of 5,278 nontyphoidal Salmonella genomes, collected over 15 years in the United States, was used to generate extreme gradient boosting (XGBoost)-based machine learning models for predicting MICs for 15 antibiotics. The MIC prediction models had an overall average accuracy of 95% within ±1 2-fold dilution step (confidence interval, 95% to 95%), an average very major error rate of 2.7% (confidence interval, 2.4% to 3.0%), and an average major error rate of 0.1% (confidence interval, 0.1% to 0.2%). The model predicted MICs with no a priori information about the underlying gene content or resistance phenotypes of the strains. By selecting diverse genomes for the training sets, we show that highly accurate MIC prediction models can be generated with less than 500 genomes. We also show that our approach for predicting MICs is stable over time, despite annual fluctuations in antimicrobial resistance gene content in the sampled genomes. Finally, using feature selection, we explore the important genomic regions identified by the models for predicting MICs. To date, this is one of the largest MIC modeling studies to be published. Our strategy for developing whole-genome sequence-based models for surveillance and clinical diagnostics can be readily applied to other important human pathogens.

Plectin protects podocytes from adriamycin-induced apoptosis and F-actin cytoskeletal disruption through the integrin α6ß4/FAK/p38 MAPK pathway.

Podocyte injury is an early pathological change characteristic of various glomerular diseases, and apoptosis and F-actin cytoskeletal disruption are typical features of podocyte injury. In this study, we found that adriamycin (ADR) treatment resulted in typical podocyte injury and repressed plectin expression. Restoring plectin expression protected against ADR-induced podocyte injury whereas siRNA-mediated plectin silencing produced similar effects as ADR-induced podocyte injury, suggesting that plectin plays a key role in preventing podocyte injury. Further analysis showed that plectin repression induced significant integrin α6ß4, focal adhesion kinase (FAK) and p38 MAPK phosphorylation. Mutating Y1494, a key tyrosine residue in the integrin ß4 subunit, blocked FAK and p38 phosphorylation, thereby alleviating podocyte injury. Inhibitor studies demonstrated that FAK Y397 phosphorylation promoted p38 activation, resulting in podocyte apoptosis and F-actin cytoskeletal disruption. In vivo studies showed that administration of ADR to rats resulted in significantly increased 24-hour urine protein levels along with decreased plectin expression and activated integrin α6ß4, FAK, and p38. Taken together, these findings indicated that plectin protects podocytes from ADR-induced apoptosis and F-actin cytoskeletal disruption by inhibiting integrin α6ß4/FAK/p38 pathway activation and that plectin may be a therapeutic target for podocyte injury-related glomerular diseases.

Identification and Characterization of Conjugative Plasmids That Encode Ciprofloxacin Resistance in Salmonella.

This study aimed to characterize novel conjugative plasmids that encode transferable ciprofloxacin resistance in Salmonella In this study, 157 nonduplicated Salmonella isolates were recovered from food products, of which 55 were found to be resistant to ciprofloxacin. Interestingly, 37 of the 55 CiprSalmonella isolates (67%) did not harbor any mutations in the quinolone resistance-determining regions (QRDR). Six Salmonella isolates were shown to carry two novel types of conjugative plasmids that could transfer the ciprofloxacin resistance phenotype to Escherichia coli J53 (azithromycin resistant [Azir]). The first type of conjugative plasmid belonged to the ∼110-kb IncFIB-type conjugative plasmids carrying qnrB-bearing and aac(6')-Ib-cr-bearing mobile elements. Transfer of the plasmid between E. coli and Salmonella could confer a ciprofloxacin MIC of 1 to 2 µg/ml. The second type of conjugative plasmid belonged to ∼240-kb IncH1/IncF plasmids carrying a single PMQR gene, qnrS Importantly, this type of conjugative ciprofloxacin resistance plasmid could be detected in clinical Salmonella isolates. The dissemination of these conjugative plasmids that confer ciprofloxacin resistance poses serious challenges to public health and Salmonella infection control.

Antimicrobial Resistance in Campylobacter Species: Mechanisms and Genomic Epidemiology.

The Campylobacter genus is a large and diverse group of Gram-negative bacteria that are known to colonize humans and other mammals, birds, reptiles, and shellfish. While it is now recognized that several emerging Campylobacter species can be associated with human disease, two species, C. jejuni and C. coli, are responsible for the vast majority of bacterial gastroenteritis in humans worldwide. Infection with C. jejuni, in particular, has also been associated with a number of extragastrointestinal manifestations and autoimmune conditions, most notably Guillain-Barré syndrome. The antimicrobial drugs of choice for the treatment of severe Campylobacter infection include macrolides, such as erythromycin, clarithromycin, or azithromycin. Fluoroquinolones, such as ciprofloxacin, are also commonly used for empirical treatment of undiagnosed diarrheal disease. However, resistance to these and other classes of antimicrobial drugs is increasing and is a major public health problem. The US Centers for Disease Control and Prevention estimates that over 300,000 infections per year are caused by drug-resistant Campylobacter. In this chapter, we discuss the taxonomy of the Campylobacter genus, the clinical and global epidemiological aspects of Campylobacter infection, with an emphasis on C. jejuni and C. coli, and issues related to the treatment of infection and antimicrobial resistance mechanisms. We further discuss the use of next-generation sequencing for the detection and surveillance of antimicrobial resistance genes.

Use of whole-genome sequencing for Campylobacter surveillance from NARMS retail poultry in the United States in 2015.

Whole genome sequencing (WGS) has become a rapid and affordable tool for public health surveillance and outbreak detection. In this study, we used the Illuminia MiSeq® to sequence 589 Campylobacter isolates obtained in 2015 from retail poultry meats as part of the National Antimicrobial Resistance Monitoring System (NARMS). WGS data were used to identify the Campylobacter species and to compare the concordance between resistance genotypes and phenotypes. WGS accurately identified 386 C. jejuni and 203 C. coli using gyrA sequence information. Ten resistance genes, including tetO, blaOXA-61, aph(2″)-Ic, aph(2″)-If, aph(2″)-Ig, aph(3')-III, ant(6)-1a, aadE, aph(3")-VIIa, and Inu(C), plus mutations in housekeeping genes (gyrA at position 86, 23S rRNA at position 2074 and 2075), were identified by WGS analysis. Overall, there was a high concordance between phenotypic resistance to a given drug and the presence of known resistance genes. Concordance between both resistance and susceptible phenotypes and genotype was 100% for ciprofloxacin, nalidixic acid, gentamicin, azithromycin, and florfenicol. A few discrepancies were observed for tetracycline, clindamycin, and telithromycin. The concordance between resistance phenotype and genotype ranged from 67.9% to 100%; whereas, the concordance between susceptible phenotype and genotype ranged from 98.0% to 99.6%. Our study demonstrates that WGS can correctly identify Campylobacter species and predict antimicrobial resistance with a high degree of accuracy.

Sequence Analysis of IncA/C and IncI1 Plasmids Isolated from Multidrug-Resistant Salmonella Newport Using Single-Molecule Real-Time Sequencing.

Multidrug-resistant (MDR) plasmids play an important role in disseminating antimicrobial resistance genes. To elucidate the antimicrobial resistance gene compositions in A/C incompatibility complex (IncA/C) plasmids carried by animal-derived MDR Salmonella Newport, and to investigate the spread mechanism of IncA/C plasmids, this study characterizes the complete nucleotide sequences of IncA/C plasmids by comparative analysis. Complete nucleotide sequencing of plasmids and chromosomes of six MDR Salmonella Newport strains was performed using PacBio RSII. Open reading frames were assigned using prokaryotic genome annotation pipeline (PGAP). To understand genomic diversity and evolutionary relationships among Salmonella Newport IncA/C plasmids, we included three complete IncA/C plasmid sequences with similar backbones from Salmonella Newport and Escherichia coli: pSN254, pAM04528, and peH4H, and additional 200 draft chromosomes. With the exception of canine isolate CVM22462, which contained an additional IncI1 plasmid, each of the six MDR Salmonella Newport strains contained only the IncA/C plasmid. These IncA/C plasmids (including references) ranged in size from 80.1 (pCVM21538) to 176.5 kb (pSN254) and carried various resistance genes. Resistance genes floR, tetA, tetR, strA, strB, sul, and mer were identified in all IncA/C plasmids. Additionally, blaCMY-2 and sugE were present in all IncA/C plasmids, excepting pCVM21538. Plasmid pCVM22462 was capable of being transferred by conjugation. The IncI1 plasmid pCVM22462b in CVM22462 carried blaCMY-2 and sugE. Our data showed that MDR Salmonella Newport strains carrying similar IncA/C plasmids clustered together in the phylogenetic tree using chromosome sequences and the IncA/C plasmids from animal-derived Salmonella Newport contained diverse resistance genes. In the current study, we analyzed genomic diversities and phylogenetic relationships among MDR Salmonella Newport using complete plasmids and chromosome sequences and provided possible spread mechanism of IncA/C plasmids in Salmonella Newport Lineage II.

Soil Moisture Retrieval from the Chinese GF-3 Satellite and Optical Data over Agricultural Fields.

Timely and accurate soil moisture information is of great importance in agricultural monitoring. The Gaofen-3 (GF-3) satellite, the first C-band multi-polarization synthetic-aperture radar (SAR) satellite in China, provides valuable data sources for soil moisture monitoring. In this study, a soil moisture retrieval algorithm was developed for the GF-3 satellite based on a backscattering coefficient simulation database. We adopted eight optical vegetation indices to determine the relationships between these indices and vegetation water content (VWC) by combining Landsat-8 data and field measurements. A backscattering coefficient database was built using an advanced integral equation model (AIEM). The effects of vegetation on backscattering coefficients were corrected using the water cloud model (WCM) to obtain the bare soil backscattering coefficient ( σ s o i l ° ). Then, soil moisture retrievals were obtained at HH, VV and HH+VV combination respectively by minimizing the observed bare soil backscattering coefficient ( σ s o i l ° ) and the AIEM-simulated backscattering coefficient ( σ soil-simu ° ). Finally, the proposed algorithm was validated in agriculture region of wheat and corn in China using ground soil moisture measurements. The results showed that the normalized difference infrared index (NDII) had the best fit with measured VWC values (R = 0.885) among the eight vegetation water indices; thus, it was adopted to correct the effects of vegetation. The proposed algorithm using GF-3 satellite data performed well in soil moisture retrieval, and the scheme combining HH and VV polarization exhibited the highest accuracy, with a root mean square error (RMSE) of 0.044 m³m-3, followed by HH polarization (RMSE = 0.049 m³m-3) and VV polarization (RMSE = 0.053 m³m-3). Therefore, the proposed algorithm has good potential to operationally estimate soil moisture from the new GF-3 satellite data.

Comparative genomic analysis and characterization of incompatibility group FIB plasmid encoded virulence factors of Salmonella enterica isolated from food sources.

BACKGROUND: The degree to which the chromosomal mediated iron acquisition system contributes to virulence of many bacterial pathogens is well defined. However, the functional roles of plasmid encoded iron acquisition systems, specifically Sit and aerobactin, have yet to be determined for Salmonella spp. In a recent study, Salmonella enterica strains isolated from different food sources were sequenced on the Illumina MiSeq platform and found to harbor the incompatibility group (Inc) FIB plasmid. In this study, we examined sequence diversity and the contribution of factors encoded on the IncFIB plasmid to the virulence of S. enterica. RESULTS: Whole genome sequences of seven S. enterica isolates were compared to genomes of serovars of S. enterica isolated from food, animal, and human sources. SeqSero analysis predicted that six strains were serovar Typhimurium and one was Heidelberg. Among the S. Typhimurium strains, single nucleotide polymorphism (SNP)-based phylogenetic analyses revealed that five of the isolates clustered as a single monophyletic S. Typhimurium subclade, while one of the other strains branched with S. Typhimurium from a bovine source. DNA sequence based phylogenetic diversity analyses showed that the IncFIB plasmid-encoded Sit and aerobactin iron acquisition systems are conserved among bacterial species including S. enterica. The IncFIB plasmid was transferred to an IncFIB plasmid deficient strain of S. enterica by conjugation. The transconjugant SE819::IncFIB persisted in human intestinal epithelial (Caco-2) cells at a higher rate than the recipient SE819. Genes of the Sit and aerobactin operons in the IncFIB plasmid were differentially expressed in iron-rich and iron-depleted growth media. CONCLUSIONS: Minimal sequence diversity was detected in the Sit and aerobactin operons in the IncFIB plasmids present among different bacterial species, including foodborne Salmonella strains. IncFIB plasmid encoded factors play a role during infection under low-iron conditions in host cells.

Identification of Plasmid-Mediated Quinolone Resistance in Salmonella Isolated from Swine Ceca and Retail Pork Chops in the United States.

Fluoroquinolones are important antimicrobial drugs used to treat human Salmonella infections, and resistance is rare in the United States for isolates from human and animal sources. Recently, a number of Salmonella isolates from swine cecal contents and retail pork products from National Antimicrobial Resistance Monitoring System (NARMS) surveillance exhibited decreased susceptibility to ciprofloxacin. We identified two qnrB19 quinolone resistance plasmids that are predominantly responsible for this phenomenon and found them distributed among several Salmonella serotypes isolated throughout the United States.

Establishing Genotypic Cutoff Values To Measure Antimicrobial Resistance in Salmonella.

Whole-genome sequencing (WGS) has transformed our understanding of antimicrobial resistance, helping us to better identify and track the genetic mechanisms underlying phenotypic resistance. Previous studies have demonstrated high correlations between phenotypic resistance and the presence of known resistance determinants. However, there has never been a large-scale assessment of how well resistance genotypes correspond to specific MICs. We performed antimicrobial susceptibility testing and WGS of 1,738 nontyphoidal Salmonella strains to correlate over 20,000 MICs with resistance determinants. Using these data, we established what we term genotypic cutoff values (GCVs) for 13 antimicrobials against Salmonella For the drugs we tested, we define a GCV as the highest MIC of isolates in a population devoid of known acquired resistance mechanisms. This definition of GCV is distinct from epidemiological cutoff values (ECVs or ECOFFs), which currently differentiate wild-type from non-wild-type strains based on MIC distributions alone without regard to genetic information. Due to the large number of isolates involved, we observed distinct MIC distributions for isolates with different resistance gene alleles, including for ciprofloxacin and tetracycline, suggesting the potential to predict MICs based on WGS data alone.