Forced synchronization of autonomous dynamical Boolean networks

"We present the design of an autonomous time-delay Boolean network realized with readily available electronic components. Through simulations and experiments that account for the detailed nonlinear response of each circuit element, we demonstrate that a network with five Boolean nodes displays complex behavior. Furthermore, we show that the dynamics of two identical networks display near-instantaneous synchronization to a periodic state when forced by a common periodic Boolean signal. A theoretical analysis of the network reveals the conditions under which complex behavior is expected in an individual network and the occurrence of synchronization in the forced networks. This research will enable future experiments on autonomous time-delay networks using readily available electronic components with dynamics on a slow enough time-scale so that inexpensive data collection systems can faithfully record the dynamics.

CTX-M Enzymes: Origin and Diffusion

CTX-M β-lactamases are considered a paradigm in the evolution of a resistance mechanism. Incorporation of different chromosomal blaCTX-M related genes from different species of Kluyvera has derived in different CTX-M clusters. In silico analyses have shown that this event has occurred at least nine times; in CTX-M-1 cluster (3), CTX-M-2 and CTX-M-9 clusters (2 each), and CTX-M-8 and CTX-M-25 clusters (1 each). This has been mainly produced by the participation of genetic mobilization units such as insertion sequences (ISEcp1 or ISCR1) and the later incorporation in hierarchical structures associated with multifaceted genetic structures including complex class 1 integrons and transposons. The capture of these blaCTX-M genes from the environment by highly mobilizable structures could have been a random event. Moreover, after incorporation within these structures, β-lactam selective force such as that exerted by cefotaxime and ceftazidime has fueled mutational events underscoring diversification of different clusters. Nevertheless, more variants of CTX-M enzymes, including those not inhibited by β-lactamase inhibitors such as clavulanic acid (IR-CTX-M variants), only obtained under in in vitro experiments, are still waiting to emerge in the clinical setting. Penetration and the later global spread of CTX-M producing organisms have been produced with the participation of the so-called “epidemic resistance plasmids” often carried in multi-drug resistant and virulent high-risk clones. All these facts but also the incorporation and co-selection of emerging resistance determinants within CTX-M producing bacteria, such as those encoding carbapenemases, depict the currently complex pandemic scenario of multi-drug resistant isolates

Insights into a Novel blaKPC-2-Encoding IncP-6 Plasmid Reveal Carbapenem-Resistance Circulation in Several Enterobacteriaceae Species from Wastewater and a Hospital Source in Spain

Untreated wastewater, particularly from hospitals and other healthcare facilities, is considered to be a reservoir for multidrug-resistant bacteria. However, its role in the spread of antibiotic resistances in the human population remains poorly investigated. We used whole genome sequencing (WGS) to analyze 25 KPC-2-producing Enterobacteriaceae isolates from sewage water collected during a 3-year period and three clinical Citrobacter freundii isolates from a tertiary hospital in the same collection area in Spain. We detected a common, recently described, IncP-6 plasmid carrying the gene blaKPC-2 in 21 isolates from both sources. The plasmid was present in diverse environmental bacterial species of opportunistic pathogens such as C. freundii, Enterobacter cloacae, Klebsiella oxytoca, and Raoultella ornithinolytica. The 40,186 bp IncP-6 plasmid encoded 52 coding sequences (CDS) and was composed of three uniquely combined regions that were derived from other plasmids recently reported in different countries of South America. The region harboring the carbapenem resistance gene (14 kb) contained a Tn3 transposon disrupted by an ISApu-flanked element and the core sequence composed by ISKpn6 / blaKPC-2 / ?blaTEM-1 / ISKpn27. We document here the presence of a novel promiscuous blaKPC-2 plasmid circulating in environmental bacteria in wastewater and human populations

Antibiotics as selectors and accelerators 1 of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem

Activity of telithromycin and comparators against bacterial pathogens isolated from 1,336 patients with clinically diagnosed acute sinusitis

BACKGROUND: Increasing antimicrobial resistance among the key pathogens responsible for community-acquired respiratory tract infections has the potential to limit the effectiveness of antibiotics available to treat these infections. Since there are regional differences in the susceptibility patterns observed and treatment is frequently empirical, the selection of antibiotic therapy may be challenging. PROTEKT, a global, longitudinal multicentre surveillance study, tracks the activity of telithromycin and comparator antibacterial agents against key respiratory tract pathogens. METHODS: In this analysis, we examine the prevalence of antibacterial resistance in 1,336 bacterial pathogens, isolated from adult and paediatric patients clinically diagnosed with acute bacterial sinusitis (ABS). RESULTS AND DISCUSSION: In total, 58.0%, 66.1%, and 55.8% of S. pneumoniae isolates were susceptible to penicillin, cefuroxime, and clarithromycin respectively. Combined macrolide resistance and reduced susceptibility to penicillin was present in 200/640 (31.3 %) of S. pneumoniae isolates (128 isolates were resistant to penicillin [MIC >= 2 mg/L], 72 intermediate [MIC 0.12–1 mg/L]) while 99.5% and 95.5% of isolates were susceptible to telithromycin and amoxicillin-clavulanate, respectively. In total, 88.2%, 87.5%, 99.4%, 100%, and 100% of H. influenzae isolates were susceptible to ampicillin, clarithromycin, cefuroxime, telithromycin, and amoxicillin-clavulanate, respectively. In vitro, telithromycin demonstrated the highest activity against M. catarrhalis (MIC(50 )= 0.06 mg/L, MIC(90 )= 0.12 mg/L). CONCLUSION: The high in vitro activity of against pathogens commonly isolated in ABS, together with a once daily dosing regimen and clinical efficacy with 5-day course of therapy, suggest that telithromycin may play a role in the empiric treatment of ABS

Dynamics of long-term colonization of respiratory tract by Haemophilus influenzae in cystic fibrosis patients shows a marked increase in hypermutable strains

The persistence and variability of 188 Haemophilus influenzae isolates in respiratory tract of 30 cystic fibrosis (CF) patients over the course of 7 years was studied. Antibiotic susceptibility testing, DNA fingerprinting, and analysis of outer membrane protein profiles were performed on all isolates. A total of 115 distinct pulsed-field gel electrophoresis profiles were identified. Ninety percent of patients were cocolonized with two or more clones over the studied period. A third of the patients were cross-colonized with one or two H. influenzae strains; 11% of the clones persisted for 3 or more months. Biotype, outer membrane protein profiles, and resistance profiles showed variation along the studied period, even in persisting clones. Four isolates (2.1%) recovered from 3 patients were type f capsulate, with three of them belonging to the same clone. beta-Lactamase production was detected in 23.9% of isolates while 7% of the beta-lactamase-negative isolates presented diminished susceptibility to ampicillin (beta-lactamase-negative ampicillin resistance phenotype). Remarkably, 21.3% of the H. influenzae isolates presented decreased susceptibility to ciprofloxacin, which was mainly observed in persisting clones. Of the H. influenzae isolates from CF patients, 18 (14.5%) were found to be hypermutable in comparison with 1 (1.4%) from non-CF patients (P < 0.0001). Ten patients (33.3%) were colonized by hypermutable strains over the study period. A multiresistance phenotype and long-term clonal persistence were significantly associated in some cases for up to 7 years. These results suggest that H. influenzae bronchial colonization in CF patients is a dynamic process, but better-adapted clones can persist for long periods of time.This work was supported by a research grant from the Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Madrid, Spain (95-98/0364). We are grateful to E. Moguel for his technical assistance and to C. García (Hospital Lozano Blesa, Zaragoza) and J. C. Alados (Hospital Virgen de las Nieves, Granada) for their cooperation

Multidisciplinary teaching of Biotechnology and Omics sciences

In the last years, there was a great boom in the Omics fields that have developed as multidisciplinary sciences. They use laboratory techniques related to Biology and Chemistry but also Bioinformatics tools. However, the developmental progress of these disciplines has led that much of undergraduate studies related to Biology have curricula that become outdated. From this point of view, it is necessary to focus the students to the fundamentals and techniques of complementary disciplines that will be essentials for the understanding of the Omics sciences. In the present work, we have developed a new teaching approach for Biochemistry, Biology and Bioinformatics students. They formed interdisciplinary working groups. These groups have prepared and presented communications about different techniques or methods in Molecular Biology, Omics or Bioinformatics participating in a technical meeting. This learning strategy “I do and I learn” has enabled to the students a first contact with the scientific communication including the approach to the scientific literature to acquire technical knowledge. The cooperation between students from different disciplines has enriched their point of view and even has been used in some practical master’s works.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Quality control for β-lactam susceptibility testing with a well-defined collection of Enterobacteriaceae and Pseudomonas aeruginosa strains in Spain

Eighteen Enterobacteriaceae and Pseudomonas aeruginosa strains, 16 of them with well-defined β-lactam re sistance mechanisms, were sent to 52 Spanish microbiology laboratories. Interpretative categories for 8 extended-spectrum β-lactams were collected. Participating laboratories used their own routine susceptibility testing procedures (88% automatic systems, 10% disk diffusion, and 2% agar dilution). Control results were established by two independent reference laboratories by applying the NCCLS microdilution method and interpretative criteria. Interpretative discrepancies were observed in 16% of the results (4.4% for cefepime, 3.0% for aztreonam, 2.8% for piperacillin-tazobactam, 1.7% for cefotaxime [CTX] and ceftazidime, 1.1% for ceftriaxone, 0.9% for meropenem, and 0.3% for imipenem). High consistency with reference values (30% major plus very major errors) was detected in K1-producing Klebsiella oxytoca, CTX-M-9-producing E. coli, and in OprD- P. aeruginosa strains. Extended- spectrum β-lactamase (ESBL) -producing strains accounted for 86% of very major errors. Recognition of the ESBL phenotype was particularly low in Enterobacter cloacae strains (<35%), due to the lack of NCCLS-specific rules in this genus. A K1-producing K. oxytoca was misidentified by 10% of laboratories as an ESBL producer. The use of well-defined resistant strains is useful for improving proficiency in susceptibility testing in clinical laboratories

An upper limit for slow-earthquake zones: self-oscillatory behavior through the Hopf bifurcation mechanism from a spring-block model under lubricated surfaces

"The complex oscillatory behavior of a spring-block model is analyzed via the Hopf bifurcation mechanism. The mathematical spring-block model includes Dieterich Ruina's friction law and Stribeck's effect. The existence of self-sustained oscillations in the transition zone where slow earthquakes are generated within the frictionally unstable region is determined. An upper limit for this region is proposed as a function of seismic parameters and frictional coefficients which are concerned with presence of fluids in the system. The importance of the characteristic length scale L, the implications of fluids, and the effects of external perturbations in the complex dynamic oscillatory behavior, as well as in the stationary solution, are take into consideration.