The bacterial cell-wall that forms a protective layer over the inner membrane is called the murein sacculus -a tightly crosslinked peptidoglycan mesh unique to bacteria. Cell-wall synthesis and recycling are critical cellular processes essential for cell growth, elongation and division. Both de novo synthesis and recycling involve an array of enzymes across all cellular compartments, namely the outer membrane, periplasm, inner membrane and cytoplasm. Due to the exclusivity of peptidoglycan in the bacterial cell-wall, these players are the target of choice for many antibacterial agents. Our current understanding of cell-wall biochemistry and biogenesis in Gram-negative organisms stems mostly from studies of Escherichia coli. An incomplete knowledge on these processes exists for the opportunistic Gram-negative pathogen, Pseudomonas aeruginosa. In this review, cell-wall synthesis and recycling in the various cellular compartments are compared and contrasted between E. coli and P. aeruginosa. Despite the fact that there is a remarkable similarity of these processes between the two bacterial species, crucial differences alter their resistance to b-lactams, fluoroquinolones and aminoglycosides. One of the common mediators underlying resistance is the amp system whose mechanism of action is closely associated with the cell-wall recycling pathway. The activation of amp genes results in expression of AmpC blactamase through its cognate regulator AmpR which further regulates multi-drug resistance. In addition, other cell-wall recycling enzymes also contribute to antibiotic resistance. This comprehensive summary of the information should spawn new ideas on how to effectively target cell-wall processes to combat the growing resistance to existing antibiotics.

Muropeptides are a group of bacterial natural products generated from the cell wall in the course of its turnover. These compounds are cell-wall recycling intermediates and also are involved in signalling functions within the bacterium. However, identity of these signalling molecules remains elusive. The identification and characterization of 20 muropeptides from Pseudomonas aeruginosa is described. The least abundant of these metabolites is present at 100 and the most abundant at 55,000 molecules per bacterium. Analysis of these muropeptides under conditions of induction of resistance to a β-lactam antibiotic identified two signaling muropeptides (N-acetylglucosamine-1,6-anhydro-N-acetylmuramyl pentapeptide and 1,6-anhydro-N-acetylmuramyl pentapeptide). Authentic synthetic samples of these metabolites were shown to activate expression of β-lactamase in the absence of any β-lactam antibiotic, hence they serve as chemical signals in this complex biochemical pathway.

There is growing evidence that Zika virus (ZIKV) infection is linked with activation of Guillan-Barré syndrome (GBS) in adults infected with the virus and microcephaly in infants following maternal infection. With the recent outpour in publications by numerous research labs, the association between microcephaly in newborns and ZIKV has become very apparent in which large numbers of viral particles were found in the central nervous tissue of an electively aborted microcephalic ZIKV-infected fetus. However, the underlying related mechanisms remain poorly understood. Thus, development of ZIKV-infected animal models are urgently required. The need to develop drugs and vaccines of high efficacy along with efficient diagnostic tools for ZIKV treatment and management raised the demand for a very selective animal model for exploring ZIKV pathogenesis and related mechanisms. In this review, we describe recent advances in animal models developed for studying ZIKV pathogenesis and evaluating potential interventions against human infection, including during pregnancy. The current research directions and the scientific challenges ahead in developing effective vaccines and therapeutics are also discussed.

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In Abbildung 2B dieser Zuschrift wurden die Produkte der Reaktionen von 2e mit PBP4 und AmpDh3 verwechselt. Die Reaktion von 2e mit PBP4 führt zu 2d,und die Reaktion von 2e mit AmpDh3 zu 2a,w ie in der korrigierten Abbildung 2unten gezeigt. In Haupttext und Abbildungslegende ergeben sich dadurch keine ¾nderungen. Figure 2. A) Chemical structures of detected muropeptides. B) The chemoenzymatic syntheses of six muropeptides.

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In Abbildung 2B dieser Zuschrift wurden die Produkte der Reaktionen von 2e mit PBP4 und AmpDh3 verwechselt. Die Reaktion von 2e mit PBP4 führt zu 2d,und die Reaktion von 2e mit AmpDh3 zu 2a,w ie in der korrigierten Abbildung 2unten gezeigt. In Haupttext und Abbildungslegende ergeben sich dadurch keine ¾nderungen.

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