ABSTRACT We analyzed 69 bacterial isolates, comprising seven species of gram-negative bacterial rods and three species of coagulase-negative staphylococci, recovered from both the hands of caretakers and their environment in households sampled in upper Manhattan. Repetitive sequence-based PCR and dendrogram analysis were used to determine strain similarity. Greater than 25% of individual species of Acinetobacter , Enterobacter , and coagulase-negative staphylococci recovered from the hands and immediate environment within each household shared the same genotype. This study is the first to demonstrate the frequency of bacteria shared within community households. These strains may serve as potential reservoirs for either community- or hospital-acquired infections.
Artificial cellular systems are minimal systems that mimic certain properties of natural cells, including signaling pathways, membranes, and metabolic pathways. These artificial cells (or protocells) can be constructed following a synthetic biology approach by assembling biomembranes, synthetic gene circuits, and cell‐free expression systems. As artificial cells are built from bottom‐up using minimal and a defined number of components, they are more amenable to predictive mathematical modeling and engineered controls when compared with natural cells. Indeed, artificial cells have been implemented as drug delivery machineries and in situ protein expression systems. Furthermore, artificial cells have been used as biomimetic systems to unveil new insights into functions of natural cells, which are otherwise difficult to investigate owing to their inherent complexity. It is our vision that the development of artificial cells would bring forth parallel advancements in synthetic biology, cell‐free systems, and in vitro systems biology. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Abstract The collective tolerance towards antimicrobial peptides (APs) is thought to occur primarily through mechanisms associated with live bacterial cells. In contrast to the focus on live cells, we discover that the LL37 antimicrobial peptide kills Escherichia coli , forming a subpopulation of dead cells that absorbs the remaining LL37 into its intracellular space. Combining mathematical modeling with population and single-cell experiments, we show that bacteria absorb LL37 at a timing that coincides with the permeabilization of their cytoplasmic membranes. Furthermore, we show that one bacterial strain can absorb LL37 and protect another strain from killing by LL37. Finally, we demonstrate that the intracellular absorption of LL37 can be reduced using a peptide adjuvant. In contrast to the existing collective tolerance mechanisms, we show that the dead-bacterial absorption of APs is a dynamic process that leads to emergent population behavior, and the work suggests new directions to enhance the efficacy of APs.
Objective: To investigate the antimicrobial resistance of clinical isolates in Kunming in 2002 for guiding the rational use of antimicrobial agents. Methods: From January to December in 2002,4 927 strains were collected from four hospitals in Kunming. Antimicrobial susceptibility was tested by disc diffusion method (K-B method ). Criteria of asssessment were according to NCCLS 2002, WHONET 5 was used for analysis of results. Results: 1 485 of 4 927 strains were gram-positive cocci (30. 1%)and 3 442 gram-negative bacilli (69. 9%). The common bacteria isolated were Escherichia coli, coagulase-negative staphylococci(CNS) ,Pseudomonas aeruginosa , Klebsiella spp. , Enterococcus faecalis , Acinetobacter spp.. 36. 3% (81/223) of Staphylococcus aureus and 72. 6% (522/719) of S. epidermidis were resistant to methicillin, all strains of staphylococci and E. faecalis were susceptible to vancomycin. Extended-spectrum beta-lactamases (ESBLs) were detected in 37. 9% and 36. 3% strains of E. coli and Klebsiella spp. , respectively. Resistance rates of ESBL-producing strains were higher than those of non ESBL-producing strains. Resistance rates of Citrobacter spp. ,Enterobacter spp. and Serratia spp. against ampicillin and amoxi cillin-clavulanic acid were 78. 6%and 94. 7%,while resistance rates to the third and forth-generation cephalosporins were much lower. Most stains of Acinetobacter spp. , P. aeruginosa were resistant to multiple antibiotics. Conclusions: Antimicrobial resistance of clinical isolates in Kunming hospitals have been a serious problem. Data of bacterial susceptibility tests are useful for the selection of antimicrobials in the treatment of bacterial infections.
Abstract Druggability refers to the capacity of a cellular target to be modulated by a small-molecule drug. To date, druggability is mainly studied by focusing on direct binding interactions between a drug and its target. However, druggability is impacted by cellular networks connected to a drug target. Here, we use computational approaches to reveal basic principles of network motifs that modulate druggability. Through quantitative analysis, we find that inhibiting self-positive feedback loop is a more robust and effective treatment strategy than inhibiting other regulations, and adding direct regulations to a drug-target generally reduces its druggability. The findings are explained through analytical solution of the motifs. Furthermore, we find that a consensus topology of highly druggable motifs consists of a negative feedback loop without any positive feedback loops, and consensus motifs with low druggability have multiple positive direct regulations and positive feedback loops. Based on the discovered principles, we predict potential genetic targets in Escherichia coli that have either high or low druggability based on their network context. Our work establishes the foundation toward identifying and predicting druggable targets based on their network topology.
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