Molecular basis of bacterial resistance to chloramphenicol and florfenicol

Chloramphenicol (Cm) and its fluorinated derivative florfenicol (Ff) represent highly potent inhibitors of bacterial protein biosynthesis. As a consequence of the use of Cm in human and veterinary medicine, bacterial pathogens of various species and genera have developed and/or acquired Cm resistance. Ff is solely used in veterinary medicine and has been introduced into clinical use in the mid-1990s. Of the Cm resistance genes known to date, only a small number also mediates resistance to Ff. In this review, we present an overview of the different mechanisms responsible for resistance to Cm and Ff with particular focus on the two different types of chloramphenicol acetyltransferases (CATs), specific exporters and multidrug transporters. Phylogenetic trees of the different CAT proteins and exporter proteins were constructed on the basis of a multisequence alignment. Moreover, information is provided on the mobile genetic elements carrying Cm or Cm/Ff resistance genes to provide a basis for the understanding of the distribution and the spread of Cm resistance--even in the absence of a selective pressure imposed by the use of Cm or Ff.     

Control of extracellular cysteine/cystine redox state by HT-29 cells is independent of cellular glutathione

Human cell lines regulate the redox state (E(h)) of the cysteine/cystine (Cys/CySS) couple in culture medium to approximately -80 mV, a value similar to the average E(h) for Cys/CySS in human plasma. The mechanisms involved in regulation of extracellular E(h) of Cys/CySS are not known, but GSH is released from tissues at rates proportional to tissue GSH concentration, and this released GSH could react with CySS to contribute to maintenance of this balance. The present study was undertaken to determine whether depletion of cellular GSH alters regulation of extracellular Cys/CySS E(h). Decrease of GSH in HT-29 cells by inhibiting synthesis with l-buthionine-[S,R]-sulfoximine showed no effect on the rate of reduction of extracellular CySS to achieve a stable E(h) for Cys/CySS in the culture medium. Limiting Cys and CySS in the culture medium also substantially decreased cellular GSH but resulted in no significant effect on extracellular Cys/CySS E(h). Addition of CySS to these cells showed that extracellular Cys/CySS E(h) approached -80 mV at 4 h while cellular GSH and extracellular GSH/GSSG E(h) recovered more slowly. Together, these results show that HT-29 cells have the capacity to regulate the extracellular Cys/CySS E(h) by mechanisms that are independent of cellular GSH. The results suggest that transport systems for Cys and CySS and/or membranal oxidoreductases could be more important than cellular GSH in regulation of extracellular Cys/CySS E(h).     

Seventy years of changes in the abundance of Danish charophytes

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Risky Courtship: Background Contrast,Ornamentation, and Display Behavior of Wolf Spiders Affect Visual Detection by Toad Predators

Males that search widely for females and perform conspicuous courtship displays run a high risk of being detected by their predators. Therefore, gains in reproductive success might be offset by increased mortality due to predation. Male brush‐legged wolf spiders (Schizocosa ocreata) with larger decorative traits (foreleg tufts) are preferred by females as mates, but are more readily detected by predators. However, predation risk may also be influenced by the interaction between components of signals and the environment in which signaling occurs. Courting male spiders were readily accepted as prey by a sympatric predator, the American toad (Anaxyrus americanus). We used video playback to tease apart the interactive effect between visual signals and the signaling environment on the ability of toads to detect courting spiders as a function of distance, background contrast, the presence or absence of male foreleg tufts, and behavioral activity. The response of toads to video sequences of male spiders was similar to their response to live male spiders. Toad response varied over distance toward spiders displayed against high contrast (sunny) vs. low contrast (shaded) backgrounds. Beyond 30 cm, more toads detected courting male spiders against light, ‘sunny’ backgrounds and detected them faster when compared to the same spider stimulus against darker, ‘shady’ backgrounds. In choice tests, toads oriented more often toward courting males with leg tufts than those without. Toad responses also varied with male spider behavior in that only videos of moving males were attacked. Latency to orient and detection by toads was significantly greater for walking males than courting males, and this effect was most evident at distances between 30 cm and 50 cm. Results supported that courting wolf spiders are at significant risk of predation by visually acute predators. Distance, background contrast, and the presence of foreleg decorations influence detection probability. Thus, the same complex visual signals that make males conspicuous and are preferred by females can make males more vulnerable as prey to toads.     

Time Course Study of Blood Pressure in Term and Preterm Infants Immediately after Birth

Objective

To describe temporal changes in systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP, respectively) in term and preterm infants immediately after birth.

Methods

Prospective observational two-center study. In term infants SBP, DBP, and MBP were assessed non-invasively every minute for the first 15 minutes, and in preterm infants every minute for the first 15 minutes, as well as at 20, 25, 30, 45, and 60 minutes after birth. Regression analyses were performed by gender and respiratory support in all neonates; and by mode of delivery, cord clamping time, and development of ultrasound-detected brain injury in preterm neonates.

Results

Term infants (n = 54) had a mean (SD) birth weight of 3298 (442) g and gestational age of 38 (1) weeks, and preterm infants (n = 94) weighed 1340 (672) g and were 30 (3) weeks gestation. Term infants’ SBP, DBP and MBP within the first 15 minutes after birth were independent of gender or respiratory support. Linear mixed regression analysis showed that preterm infants, who were female, born vaginally, had delayed cord clamping and did not require positive pressure ventilation nor develop periventricular injury or ventriculomegaly, had significantly higher SBP, DBP, and MBP at some measurement points within the first hour after birth.

Conclusions

We present novel reference ranges of BP immediately after birth in a cohort of term and preterm neonates. They may aid in optimization of cardiovascular support during early transition at all gestations.     

KnotInFrame: prediction of -1 ribosomal frameshift events

Programmed -1 ribosomal frameshift (-1 PRF) allows for alternative reading frames within one mRNA. First found in several viruses, it is now believed to exist in all kingdoms of life. Strong stimulators for -1 PRF are a heptameric slippery site and an RNA pseudoknot. Here, we present a new algorithm KnotInFrame, for the automatic detection of -1 PRF signals from genomic sequences. It finds the frameshifting stimulators by means of a specialized RNA-pseudoknot folding program, fast enough for genome-wide analyses. Evaluations on known -1 PRF signals demonstrate a high sensitivity.     

Comparative membrane proteome analysis of three Borrelia species

The versatility of the surface of Borrelia, the causative agent of Lyme borreliosis, is very important in host-pathogen interactions allowing bacteria to survive in ticks and to persist in a mammalian environment. To identify the surface proteome of Borrelia, we have performed a large comparative proteomic analysis on the three most important pathogenic Borrelia species, namely B. burgdorferi (strain B31), B. afzelii (strain K78), and B. garinii (strain PBi). Isolation of membrane proteins was performed by using three different approaches: (i) a detergent-based fractionation of outer membrane proteins; (ii) a trypsin-based partial shedding of outer cell surface proteins; (iii) biotinylation of membrane proteins and preparation of the biotin-labelled fraction using streptavidin. Proteins derived from the detergent-based fractionation were further sub-fractionated by heparin affinity chromatography since heparin-like molecules play an important role for microbial entry into human cells. All isolated proteins were analysed using either a gel-based liquid chromatography (LC)-MS/MS technique or by two-dimensional (2D)-LC-MS/MS resulting in the identification of 286 unique proteins. Ninety seven of these were found in all three Borrelia species, representing potential targets for a broad coverage vaccine for the prevention of Lyme borreliosis caused by the different Borrelia species.