Evolution of Salmonella enterica Virulence via Point Mutations in the Fimbrial Adhesin

Whereas the majority of pathogenic Salmonella serovars are capable of infecting many different animal species, typically producing a self-limited gastroenteritis, serovars with narrow host-specificity exhibit increased virulence and their infections frequently result in fatal systemic diseases. In our study, a genetic and functional analysis of the mannose-specific type 1 fimbrial adhesin FimH from a variety of serovars of Salmonella enterica revealed that specific mutant variants of FimH are common in host-adapted (systemically invasive) serovars. We have found that while the low-binding shear-dependent phenotype of the adhesin is preserved in broad host-range (usually systemically non-invasive) Salmonella, the majority of host-adapted serovars express FimH variants with one of two alternative phenotypes: a significantly increased binding to mannose (as in S. Typhi, S. Paratyphi C, S. Dublin and some isolates of S. Choleraesuis), or complete loss of the mannose-binding activity (as in S. Paratyphi B, S. Choleraesuis and S. Gallinarum). The functional diversification of FimH in host-adapted Salmonella results from recently acquired structural mutations. Many of the mutations are of a convergent nature indicative of strong positive selection. The high-binding phenotype of FimH that leads to increased bacterial adhesiveness to and invasiveness of epithelial cells and macrophages usually precedes acquisition of the non-binding phenotype. Collectively these observations suggest that activation or inactivation of mannose-specific adhesive properties in different systemically invasive serovars of Salmonella reflects their dynamic trajectories of adaptation to a life style in specific hosts. In conclusion, our study demonstrates that point mutations are the target of positive selection and, in addition to horizontal gene transfer and genome degradation events, can contribute to the differential pathoadaptive evolution of Salmonella

Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin Ii-Induced Hypertension.

BACKGROUND: Resolution of inflammation is orchestrated by specialized pro-resolving mediators (SPMs), and this would be impaired in some cardiovascular diseases. Among SPMs, resolvins (Rv) have beneficial effects in cardiovascular pathologies, but little is known about their effect on cardiovascular damage in hypertension. METHODS: Aorta, small mesenteric arteries, heart, and peritoneal macrophages were taken from C57BL/6J mice, infused or not with Angiotensin II (AngII 1.44 mg/kg/day, 14 days) in presence or absence of RvD2 (100 ng/mice, every second day) starting 1 day before or 7 days after AngII infusion. RESULTS: Enzymes and receptors involved in SPMs biosynthesis and signaling were increased in aorta or heart from AngII-infused mice. We also observed a differential regulation of SPMs in heart from these mice. Preventive treatment with RvD2 partially avoided AngII-induced hypertension and protected the heart and large and small vessels against functional and structural alterations induced by AngII. RvD2 increased the availability of vasoprotective factors, modified SPMs profile, decreased cardiovascular fibrosis, and increased the infiltration of pro-resolving macrophages. When administered in hypertensive animals with established cardiovascular damage, RvD2 partially improved cardiovascular function and structure, decreased fibrosis, reduced the infiltration of neutrophils, and shifted macrophage phenotype toward a pro-resolving phenotype. CONCLUSIONS: There is a disbalance between proinflammatory and resolution mediators in hypertension. RvD2 protects cardiovascular function and structure when administered before and after the development of hypertension by modulating vascular factors, fibrosis and inflammation. Activating resolution mechanisms by treatment with RvD2 may represent a novel therapeutic strategy for the treatment of hypertensive cardiovascular disease

Antarctic crabs: invasion or endurance?

Recent scientific interest following the “discovery” of lithodid crabs around Antarctica has centred on a hypothesis that these crabs might be poised to invade the Antarctic shelf if the recent warming trend continues, potentially decimating its native fauna. This “invasion hypothesis” suggests that decapod crabs were driven out of Antarctica 40–15 million years ago and are only now returning as “warm” enough habitats become available. The hypothesis is based on a geographically and spatially poor fossil record of a different group of crabs (Brachyura), and examination of relatively few Recent lithodid samples from the Antarctic slope. In this paper, we examine the existing lithodid fossil record and present the distribution and biogeographic patterns derived from over 16,000 records of Recent Southern Hemisphere crabs and lobsters. Globally, the lithodid fossil record consists of only two known specimens, neither of which comes from the Antarctic. Recent records show that 22 species of crabs and lobsters have been reported from the Southern Ocean, with 12 species found south of 60°S. All are restricted to waters warmer than 0°C, with their Antarctic distribution limited to the areas of seafloor dominated by Circumpolar Deep Water (CDW). Currently, CDW extends further and shallower onto the West Antarctic shelf than the known distribution ranges of most lithodid species examined. Geological evidence suggests that West Antarctic shelf could have been available for colonisation during the last 9,000 years. Distribution patterns, species richness, and levels of endemism all suggest that, rather than becoming extinct and recently re-invading from outside Antarctica, the lithodid crabs have likely persisted, and even radiated, on or near to Antarctic slope. We conclude there is no evidence for a modern-day “crab invasion”. We recommend a repeated targeted lithodid sampling program along the West Antarctic shelf to fully test the validity of the “invasion hypothesis”