Variable Carbon Catabolism among Salmonella enterica Serovar Typhi Isolates

BACKGROUND: Salmonella enterica serovar Typhi (S. Typhi) is strictly a human intracellular pathogen. It causes acute systemic (typhoid fever) and chronic infections that result in long-term asymptomatic human carriage. S. Typhi displays diverse disease manifestations in human infection and exhibits high clonality. The principal factors underlying the unique lifestyle of S. Typhi in its human host during acute and chronic infections remain largely unknown and are therefore the main objective of this study. METHODOLOGY/PRINCIPAL FINDINGS: To obtain insight into the intracellular lifestyle of S. Typhi, a high-throughput phenotypic microarray was employed to characterise the catabolic capacity of 190 carbon sources in S. Typhi strains. The success of this study lies in the carefully selected library of S. Typhi strains, including strains from two geographically distinct areas of typhoid endemicity, an asymptomatic human carrier, clinical stools and blood samples and sewage-contaminated rivers. An extremely low carbon catabolic capacity (27% of 190 carbon substrates) was observed among the strains. The carbon catabolic profiles appeared to suggest that S. Typhi strains survived well on carbon subtrates that are found abundantly in the human body but not in others. The strains could not utilise plant-associated carbon substrates. In addition, α-glycerolphosphate, glycerol, L-serine, pyruvate and lactate served as better carbon sources to monosaccharides in the S. Typhi strains tested. CONCLUSION: The carbon catabolic profiles suggest that S. Typhi could survive and persist well in the nutrient depleted metabolic niches in the human host but not in the environment outside of the host. These findings serve as caveats for future studies to understand how carbon catabolism relates to the pathogenesis and transmission of this pathogen

Is acupuncture "stimulation" a misnomer? A case for using the term " blockade"

Background: The term used most frequently in the literature to describe acupuncture's effects is " stimulation" which may be used to describe either (or both) the direct stimulus applied to a needle as well as putative stimulation of the nervous system, despite little published evidence describing what is actually being stimulated. In contrast, recent published work has suggested that acupuncture may, in fact be inhibitory at a peripheral level, acting by blocking neural transmission.Discussion: The suggestion that acupuncture exerts its effects through peripheral neural blockade is supported by recent evidence explaining related techniques including low level laser and capsaicin at acupoints. It also explains acupuncture's effect on painful and non-painful conditions and both Eastern and Western concepts of acupuncture. There is a need for additional work to elucidate acupuncture's mechanism of action, and the suggestion that it acts through neural blockade should prompt further research in this direction.Summary: If the term " blockade" were applied to acupuncture, this would, likely, be expected to promote this minimally invasive technique, and, potentially, bring it into mainstream clinical practice for pain management as well as other therapeutic applications. © 2013 Silberstein; licensee BioMed Central Ltd

Lack of the PGA exopolysaccharide in Salmonella as an adaptive trait for survival in the host

Many bacteria build biofilm matrices using a conserved exopolysaccharide named PGA or PNAG (poly-β-1,6-N-acetyl-D-glucosamine). Interestingly, while E. coli and other members of the family Enterobacteriaceae encode the pgaABCD operon responsible for PGA synthesis, Salmonella lacks it. The evolutionary force driving this difference remains to be determined. Here, we report that Salmonella lost the pgaABCD operon after the divergence of Salmonella and Citrobacter clades, and previous to the diversification of the currently sequenced Salmonella strains. Reconstitution of the PGA machinery endows Salmonella with the capacity to produce PGA in a cyclic dimeric GMP (c-di-GMP) dependent manner. Outside the host, the PGA polysaccharide does not seem to provide any significant benefit to Salmonella: resistance against chlorine treatment, ultraviolet light irradiation, heavy metal stress and phage infection remained the same as in a strain producing cellulose, the main biofilm exopolysaccharide naturally produced by Salmonella. In contrast, PGA production proved to be deleterious to Salmonella survival inside the host, since it increased susceptibility to bile salts and oxidative stress, and hindered the capacity of S. Enteritidis to survive inside macrophages and to colonize extraintestinal organs, including the gallbladder. Altogether, our observations indicate that PGA is an antivirulence factor whose loss may have been a necessary event during Salmonella speciation to permit survival inside the host.This work was supported by the Spanish Ministry of Economy and Competitiveness grants BIO2014-53530-R and SAF2014-56716-REDT (http://www.mineco.gob.es/portal/site/mineco/?lang_choosen=en). JV was supported by Ramon y Cajal (RYC-2009-03948) contract from the Spanish Ministry of Economy and Competitiveness