Antibiotic resistance patterns and beta-lactamase identification in Escherichia coli isolated from young children in rural Limpopo Province, South Africa: The MAL-ED cohort

Background. Antibiotic resistance is a growing problem worldwide. Mechanisms of resistance vary, and some can confer resistance to multiple classes of antibiotics.Objective. To characterise the antibiotic resistance profiles of Escherichia coli isolates obtained from stool samples of young rural children exposed or unexposed to antibiotics.Methodology. The samples were collected from children aged 4 - 12 months who were participants in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) project at the South Africa research site. We isolated 87 E. coli samples (clones) from 65 individual participants, all of which were subjected to disc diffusion assay to determine resistance. We characterised the minimum inhibitory concentration of antibiotics in a subset of strains as well as the mechanism by which these strains were resistant to beta-lactam antibiotics.Results. Our results revealed high resistance rates to co-trimoxazole (54.0%), penicillin (47.1%) and tetracycline (44.8%) in our isolates, and indicated that the beta-lactamase TEM-1 is a prevalent source of beta-lactam resistance. We also identified two isolates with the extended-spectrum beta-lactamase CTX-M-14.Conclusions. This study identified antibiotic-resistant E. coli in children with and without prior exposure to antibiotics, with some isolates showing resistance to multiple classes of antibiotics. Clinicians should bear in mind that transmission of extended-spectrum beta-lactamase-resistant E. coli exists at the community level, and that children as young as 2 years may be harbouring these resistant phenotypes

Antibiotic resistance patterns and beta-lactamase identification in Escherichia coli isolated from young children in rural Limpopo Province, South Africa: The MAL-ED cohort

Background. Antibiotic resistance is a growing problem worldwide. Mechanisms of resistance vary, and some can confer resistance to multiple classes of antibiotics. Objective. To characterise the antibiotic resistance profiles of Escherichia coli isolates obtained from stool samples of young rural children exposed or unexposed to antibiotics. Methodology. The samples were collected from children aged 4 - 12 months who were participants in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) project at the South Africa research site. We isolated 87 E. coli samples (clones) from 65 individual participants, all of which were subjected to disc diffusion assay to determine resistance. We characterised the minimum inhibitory concentration of antibiotics in a subset of strains as well as the mechanism by which these strains were resistant to beta-lactam antibiotics. Results. Our results revealed high resistance rates to co-trimoxazole (54.0%), penicillin (47.1%) and tetracycline (44.8%) in our isolates, and indicated that the beta-lactamase TEM-1 is a prevalent source of beta-lactam resistance. We also identified two isolates with the extended-spectrum beta-lactamase CTX-M-14. Conclusions. This study identified antibiotic-resistant E. coli in children with and without prior exposure to antibiotics, with some isolates showing resistance to multiple classes of antibiotics. Clinicians should bear in mind that transmission of extended-spectrum beta-lactamase-resistant E. coli exists at the community level, and that children as young as 2 years may be harbouring these resistant phenotypes

Discovery of Western European R1b1a2 Y Chromosome Variants in 1000 Genomes Project Data: An Online Community Approach

The authors have used an online community approach, and tools that were readily available via the Internet, to discover genealogically and therefore phylogenetically relevant Y-chromosome polymorphisms within core haplogroup R1b1a2-L11/S127 (rs9786076). Presented here is the analysis of 135 unrelated L11 derived samples from the 1000 Genomes Project. We were able to discover new variants and build a much more complex phylogenetic relationship for L11 sub-clades. Many of the variants were further validated using PCR amplification and Sanger sequencing. The identification of these new variants will help further the understanding of population history including patrilineal migrations in Western and Central Europe where R1b1a2 is the most frequent haplogroup. The fine-grained phylogenetic tree we present here will also help to refine historical genetic dating studies. Our findings demonstrate the power of citizen science for analysis of whole genome sequence data

Regional chromosomal localization of the human gene for galactose-1-phosphate uridyltransferase

In the progeny of somatic cell hybrids formed by fusion of human lymphocytes and Chinese hamster mutant cells, a single human chromosome A2 was selectively retained when grown in appropriate medium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47607/1/439_2004_Article_BF00393609.pd

Human Integrin α3β1 Regulates TLR2 Recognition of Lipopeptides from Endosomal Compartments

Toll-like receptor (TLR)-2/TLR1 heterodimers recognize bacterial lipopeptides and initiate the production of inflammatory mediators. Adaptors and co-receptors that mediate this process, as well as the mechanisms by which these adaptors and co-receptors function, are still being discovered.Using shRNA, blocking antibodies, and fluorescent microscopy, we show that U937 macrophage responses to the TLR2/1 ligand, Pam(3)CSK(4), are dependent upon an integrin, α(3)β(1). The mechanism for integrin α(3)β(1) involvement in TLR2/1 signaling is through its role in endocytosis of lipopeptides. Using inhibitors of endosomal acidification/maturation and physical tethering of the ligand, we show that the endocytosis of Pam(3)CSK(4) is necessary for the complete TLR2/1-mediated pro-inflammatory cytokine response. We also show that TLR2/1 signaling from the endosome results in the induction of different inflammatory mediators than TLR2/1 signaling from the plasma membrane.Here we identify integrin α(3)β(1) as a novel regulator for the recognition of bacterial lipopeptides. We demonstrate that induction of a specific subset of cytokines is dependent upon integrin α(3)β(1)-mediated endocytosis of the ligand. In addition, we address an ongoing controversy regarding endosomal recognition of bacterial lipopeptides by demonstrating that TLR2/1 signals from within endosomal compartments as well as the plasma membrane, and that downstream responses may differ depending upon receptor localization. We propose that the regulation of endosomal TLR2/1 signaling by integrin α(3)β(1) serves as a mechanism for modulating inflammatory responses