Integrated genetic and metabolic landscapes predict vulnerabilities of temozolomide resistant glioblastoma cells

Metabolic reprogramming and its molecular underpinnings are critical to unravel the duality of cancer cell function and chemo-resistance. Here, we use a constraints-based integrated approach to delineate the interplay between metabolism and epigenetics, hardwired in the genome, to shape temozolomide (TMZ) resistance. Differential metabolism was identified in response to TMZ at varying concentrations in both the resistant neurospheroidal (NSP) and the susceptible (U87MG) glioblastoma cell-lines. The genetic basis of this metabolic adaptation was characterized by whole exome sequencing that identified mutations in signaling pathway regulators of growth and energy metabolism. Remarkably, our integrated approach identified rewiring in glycolysis, TCA cycle, malate aspartate shunt, and oxidative phosphorylation pathways. The differential killing of TMZ resistant NSP by Rotenone at low concentrations with an IC50 value of 5 nM, three orders of magnitude lower than for U87MG that exhibited an IC50 value of 1.8 mM was thus identified using our integrated systems-based approach.

Differential Killing Activity of Cetylpyridinium Chloride with or without Bacto Neutralizing Buffer Quench against Firmly Adhered Salmonella Gaminara and Shigella sonnei on Cut Lettuce Stored at 4°C

Cetylpyridinium chloride (CPC) activity was quenched with Bacto neutralizing buffer on inoculated cut iceberg lettuce. This protocol permitted comparison of the numbers of Salmonella Gaminara– or Shigella sonnei–inoculated cells on lettuce that survived 1 min of CPC treatment. Cut lettuce was inoculated with about 6 log of Salmonella or 9 log of Shigella and stored in Whirl-Pak bags at 4°C for up to 4 days. Loosely adhered pathogen cells were washed off before CPC treatment. Firmly adhered cells of Salmonella Gaminara or S. sonnei on cut iceberg lettuce survived treatment with CPC even at the 0.4% CPC level if the CPC activity was quenched after 1 min by adding Bacto neutralizing buffer. The results confirm that there is extended killing activity of residual CPC against Salmonella Gaminara or S. sonnei if the residual CPC remaining in contact with the lettuce after the initial 1-min wash is not quenched. The CPC treatment was useful in reducing the numbers of these target pathogens on lettuce.