Explore the vast range of titles available.

Background Over one million yearly deaths are attributable to Streptococcus pneumoniae and people living with HIV are particularly vulnerable. Emerging penicillin non-susceptible Streptococcus pneumoniae (PNSP) challenges therapy of pneumococcal disease. The aim of this study was to determine the mechanisms of antibiotic resistance among PNSP isolates by next generation sequencing. Methods We assessed 26 PNSP isolates obtained from the nasopharynx from 537 healthy human immunodeficiency virus (HIV) infected adults in Dar es Salaam, Tanzania, participating in the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890, registered on 23rd March, 2017). Next generation whole genome sequencing on the Illumina platform was used to identify mechanisms of resistance to antibiotics among PNSP. Results Fifty percent (13/26) of PNSP were resistant to erythromycin, of these 54% (7/13) and 46% (6/13) had MLS B phenotype and M phenotype respectively. All erythromycin resistant PNSP carried macrolide resistance genes; six isolates had mef (A)- msr (D), five isolates had both erm (B) and mef (A)- msr (D) while two isolates carried erm (B) alone. Isolates harboring the erm (B) gene had increased MIC (> 256 µg/mL) towards macrolides, compared to isolates without erm (B) gene (MIC 4-12 µg/mL) p < 0.001. Using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, the prevalence of azithromycin resistance was overestimated compared to genetic correlates. Tetracycline resistance was detected in 13/26 (50%) of PNSP and all the 13 isolates harbored the tet (M) gene. All isolates carrying the tet (M) gene and 11/13 isolates with macrolide resistance genes were associated with the mobile genetic element Tn 6009 transposon family. Of 26 PNSP isolates, serotype 3 was the most common (6/26), and sequence type ST271 accounted for 15% (4/26). Serotypes 3 and 19 displayed high-level macrolide resistance and frequently carried both macrolide and tetracycline resistance genes. Conclusion The erm (B) and mef (A)- msr (D) were common genes conferring resistance to MLS B in PNSP. Resistance to tetracycline was conferred by the tet (M) gene. Resistance genes were associated with the Tn 6009 transposon.

The study objective was to determine the effects of two treatment regimens on quantities of ceftiofur and tetracycline resistance genes in feedlot cattle. The two regimens were ceftiofur crystalline-free acid (CCFA) administered to either one or all steers within a pen and subsequent feeding/not feeding of therapeutic doses of chlortetracycline. A 26-day randomized controlled field trial was conducted on 176 steers. Real-time PCR was used to quantify bla CMY-2 , bla CTX-M , tet (A), tet (B) and 16S rRNA gene copies/gram of feces from community DNA. A significant increase in ceftiofur resistance and a decrease in tetracycline resistance elements were observed among the treatment groups in which all steers received CCFA treatment, expressed as gene copies/gram of feces. Subsequent chlortetracycline administration led to rapid expansion of both ceftiofur and tetracycline resistance gene copies/gram of feces. Our data suggest that chlortetracycline is contraindicated when attempting to avoid expansion of resistance to critically important third-generation cephalosporins.

A metagenomic approach and network analysis was used to investigate the wide-spectrum profiles of antibiotic resistance genes (ARGs) and their co-occurrence patterns in 50 samples from 10 typical environments. In total, 260 ARG subtypes belonging to 18 ARG types were detected with an abundance range of 5.4 × 10 −6 –2.2 × 10 −1 copy of ARG per copy of 16S-rRNA gene. The trend of the total ARG abundances in environments matched well with the levels of anthropogenic impacts on these environments. From the less impacted environments to the seriously impacted environments, the total ARG abundances increased up to three orders of magnitude, that is, from 3.2 × 10 −3 to 3.1 × 10 0 copy of ARG per copy of 16S-rRNA gene. The abundant ARGs were associated with aminoglycoside, bacitracin, β-lactam, chloramphenicol, macrolide-lincosamide-streptogramin, quinolone, sulphonamide and tetracycline, in agreement with the antibiotics extensively used in human medicine or veterinary medicine/promoters. The widespread occurrences and abundance variation trend of vancomycin resistance genes in different environments might imply the spread of vancomycin resistance genes because of the selective pressure resulting from vancomycin use. The simultaneous enrichment of 12 ARG types in adult chicken faeces suggests the coselection of multiple ARGs in this production system. Non-metric multidimensional scaling analysis revealed that samples belonging to the same environment generally possessed similar ARG compositions. Based on the co-occurrence pattern revealed by network analysis, tet M and aminoglycoside resistance protein, the hubs of the ARG network, are proposed to be indicators to quantitatively estimate the abundance of 23 other co-occurring ARG subtypes by power functions.

Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet (X) has been shown to encode a flavin-dependent monooxygenase that modifies tigecycline 1 , 2 . Here, we report two unique mobile tigecycline-resistance genes, tet (X3) and tet (X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet (X3) and tet (X4) increase (by 64–128-fold) the tigecycline minimal inhibitory concentration values for Escherichia coli , Klebsiella pneumoniae and Acinetobacter baumannii . In addition, both Tet(X3) ( A. baumannii ) and Tet(X4) ( E. coli ) significantly compromise tigecycline in in vivo infection models. Both tet (X3) and tet (X4) are adjacent to insertion sequence IS Vsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet (X3) and tet (X4) are globally present in clinical bacteria—even in the same bacteria as bla NDM-1 , resulting in resistance to both tigecycline and carbapenems. Our findings suggest that both the surveillance of tet (X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention. Mobile tet (X3) and tet (X4) genes are identified on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated from humans, meat for consumption and animals that confer resistance to tetracyclines, including tigecycline, eravacycline and omadacycline.

Infections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet (W) gene is under positive selective pressure. Our findings reveal that tet (W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health. Here, the authors combine in silico analysis of 435 genomes of ruminal bacteria and archaea with transcriptomics and in vitro assays to investigate the distribution, expression and mobility of antibiotic resistance genes within the ruminal microbiota, finding that the tet (W) gene is under positive selective pressure.

Background Antibiotic resistance genes (ARGs) are widespread but cause problems only when present in pathogens. Environments where selection and transmission of antibiotic resistance frequently take place are likely to be characterized by high abundance and diversity of horizontally transferable ARGs. Large-scale quantitative data on ARGs is, however, lacking for most types of environments, including humans and animals, as is data on resistance genes to potential co-selective agents, such as biocides and metals. This paucity prevents efficient identification of risk environments. Results We provide a comprehensive characterization of resistance genes, mobile genetic elements (MGEs) and bacterial taxonomic compositions for 864 metagenomes from humans ( n  = 350), animals ( n  = 145) and external environments ( n  = 369), all deeply sequenced using Illumina technology. Environment types showed clear differences in both resistance profiles and bacterial community compositions. Human and animal microbial communities were characterized by limited taxonomic diversity and low abundance and diversity of biocide/metal resistance genes and MGEs but a relatively high abundance of ARGs. In contrast, external environments showed consistently high taxonomic diversity which in turn was linked to high diversity of both biocide/metal resistance genes and MGEs. Water, sediment and soil generally carried low relative abundance and few varieties of known ARGs, whereas wastewater/sludge was on par with the human gut. The environments with the largest relative abundance and/or diversity of ARGs, including genes encoding resistance to last resort antibiotics, were those subjected to industrial antibiotic pollution and a limited set of deeply sequenced air samples from a Beijing smog event. Conclusions Our study identifies air and antibiotic-polluted environments as under-investigated transmission routes and reservoirs for antibiotic resistance. The high taxonomic and genetic diversity of external environments supports the hypothesis that these also form vast sources of unknown resistance genes, with potential to be transferred to pathogens in the future.

The history of clinical resistance to tetracycline antibiotics is characterized by cycles whereby the deployment of a new generation of drug molecules is quickly followed by the discovery of a new mechanism of resistance. This suggests mechanism-specific selection by each tetracycline generation; however, the evolutionary dynamics of this remain unclear. Here, we evaluate 24 recombinant Escherichia coli strains expressing tetracycline resistance genes from each mechanism (efflux pumps, ribosomal protection proteins, and enzymatic inactivation) in the context of each tetracycline generation. We employ a high-throughput barcode sequencing protocol that can discriminate between strains in mixed culture and quantify their relative abundances. We find that each mechanism is preferentially selected for by specific antibiotic generations, leading to their expansion. Remarkably, the minimum inhibitory concentration associated with individual genes is secondary to resistance mechanism for inter-mechanism relative fitness, but it does explain intra-mechanism relative fitness. These patterns match the history of clinical deployment of tetracycline drugs and resistance discovery in pathogens. Bacteria can use different mechanisms to become resistant to the same antibiotic class. Here, the authors study bacterial strains that express genes conferring tetracycline resistance via different mechanisms, and find that each mechanism is preferentially selected for by specific tetracycline generations.

The distribution of potential clinically relevant antibiotic resistance (AR) genes across soil, water, animal, plant and human microbiomes is not well understood. We aimed to investigate if there were differences in the distribution and relative abundances of resistance genes across a variety of ecological niches. All sequence reads (human, animal, water, soil, plant and insect metagenomes) from the MG-RAST database were downloaded and assembled into a local sequence database. We show that there are many reservoirs of the basic form of resistance genes e.g. bla TEM, but the human and mammalian gut microbiomes contain the widest diversity of clinically relevant resistance genes using metagenomic analysis. The human microbiomes contained a high relative abundance of resistance genes, while the relative abundances varied greatly in the marine and soil metagenomes, when datasets with greater than one million genes were compared. While these results reflect a bias in the distribution of AR genes across the metagenomes, we note this interpretation with caution. Metagenomics analysis includes limits in terms of detection and identification of AR genes in complex and diverse microbiome population. Therefore, if we do not detect the AR gene is it in fact not there or just below the limits of our techniques? Distribution and relative abundances of antibiotic resistance genes across the world from the ocean to the human gut and everywhere in between. Graphical Abstract Figure. Distribution and relative abundances of antibiotic resistance genes across the world from the ocean to the human gut and everywhere in between.

Sediment is an ideal medium for the aggregation and dissemination of antibiotics and antibiotic resistance genes (ARGs). The levels of antibiotics and ARGs in Honghu Lake and East Dongting Lake of central China were investigated in this study. The concentrations of eight antibiotics (four sulfonamides and four tetracyclines) in Honghu Lake were in the range 90.00–437.43 µg kg⁻¹ (dry weight (dw)) with mean value of 278.21 µg kg⁻¹ dw, which was significantly higher than those in East Dongting Lake (60.02–321.04 µg kg⁻¹ dw, mean value of 195.70 µg kg⁻¹ dw). Among the tested three sulfonamide resistance genes (sul) and eight tetracycline resistance genes (tet), sul 1, sul 2, tetA, tetC, and tetM had 100 % detection frequency in sediment samples of East Dongting Lake, while only sul1, sul2, and tetC were observed in all samples of Honghu Lake. The relative abundance of sul2 was higher than that of sul1 at p < 0.05 level in both lakes. The relative abundance of tet genes in East Dongting Lake was in the following order: tetM > tetB > tetC > tetA. Therelativeabundanceofsul1, sul2, and tetC in East Dongting Lake was significantly higher than those in Honghu Lake. The abundance of background bacteria may play an important role in the horizontal spread of sul2 andtetC genes in Honghu Lake and sul1 in East Dongting Lake, respectively. Redundancy analysis indicated that tetracyclines may play a more important role than sulfonamides in the abundance of sul1, sul2, and tetC gensin Honghu Lake and East Dongting Lake.

Streptococcus agalactiae (Group B Streptococcus , GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. Group B streptococci (GBS) started causing serious infections in newborn babies in the 1960s. Here, the authors show that the emergence of GBS diseases was associated with worldwide dissemination of a few clones that were resistant to tetracycline, an antibiotic that became widely used in the 1950s.