Acinetobacter baumannii is an opportunistic bacterial pathogen primarily associated with hospital-acquired infections. The recent increase in incidence, largely associated with infected combat troops returning from conflict zones, coupled with a dramatic increase in the incidence of multidrug-resistant (MDR) strains, has significantly raised the profile of this emerging opportunistic pathogen. Herein, we provide an overview of the pathogen, discuss some of the major factors that have led to its clinical prominence and outline some of the novel therapeutic strategies currently in development.

Up to 80% of infants infected with Cronobacter sakazakii die within days of birth, making this emerging gastrointestinal pathogen a serious cause for concern. The mode of transmission most often associated with C. sakazakii infection is powdered infant formula (PIF), which typically has a water activity (aw) of ca 0.2--inhospitable to most bacterial pathogens. In the current study a comparative genomic approach was used to investigate the distinctive ability of this pathogen to survive and persist in such low aW conditions. A comprehensive review of the mechanisms involved in bacterial osmoadaptation was followed by an exhaustive homology transfer based approach to identify putative osmotolerance loci in the C. sakazakii genome. In total 53 osmotoleance loci were identified, including both hyper- and hypo-osmotic stress response systems, helping to construct a concise overview of the C. sakazakii osmotolerance response. Interestingly, while C. sakazakii contains homologues of all the principal osmotolerance loci of Escherichia coli; a key difference is that C. sakazakii contains multiple copies of certain osmotolerance loci; including seven copies of the E. coli proP homologue and two copies of OpuC--a multi component carnitine uptake system associated with Listeria monocytogenes and which has also been found to transport other compatible solutes such as glycine betaine, proline, ectoine and choline. Furthermore, the osmotic stress response of C. sakazakii appears to be regulated at the transcriptional, translational and post-translational levels, with RpoS most likely functioning as the global transcriptional regulator of the osmotolerance response.

These authors contributed equally to this work.

Bacteria respond to elevated osmolality by the accumulation of a range of low molecular weight molecules, known as compatible solutes (owing to their compatibility with the cells' normal physiology at high internal concentrations). The neonatal pathogen Cronobacter sakazakii is uniquely osmotolerant, surviving in powdered infant formula (PIF) which typically has a water activity (aw) of 0.2 – inhospitable to most micro-organisms. Mortality rates of up to 80% in infected infants have been recorded making C. sakazakii a serious cause for concern. In silico analysis of the C. sakazakii BAA-894 genome revealed seven copies of the osmolyte uptake system ProP. Herein, we test the physiological role of each of these homologues following heterologous expression against an osmosensitive Escherichia coli host.

Betaine uptake in Listeria monocytogenes is mediated by three independent transport systems, the simplest of which in genetic terms is the secondary transporter BetL. Using a random mutagenesis approach, based on the E. coli XL1 Red mutator strain, we identified a single point mutation in a putative promoter region upstream of the BetL coding region which leads to a significant increase in betL transcript levels under osmo- and chill-stress conditions and a concomitant increase in stress tolerance. Furthermore, the mutation appears to counter the heretofore unreported “twisted” cell morphology observed for L. monocytogenes grown at elevated osmolarities in tryptone soy broth.