Cells Producing Their Own Nemesis: Understanding Methylglyoxal Metabolism

Methylglyoxal, which is technically known as 2-oxopropanal or pyruvaldehyde, shows typical reactions of carbonyl compounds as it has both an aldehyde and a ketone functional group. It is an extremely cytotoxic physiological metabolite, which is generated by both enzymatic and nonenzymatic reactions. The deleterious nature of the compound is due to its ability to glycate and crosslink macromolecules like protein and DNA, respectively. However, despite having toxic effects on cellular processes, methylglyoxal retains its efficacy as an anticancer drug. Indeed, methylglyoxal is one of the well-known anticancer therapeutic agents used in the treatment. Several studies on methylglyoxal biology revolve around the manifestations of its inhibitory effects and toxicity in microbial growth and diabetic complications, respectively. Here, we have revisited the chronology of methylglyoxal research with emphasis on metabolism of methylglyoxal and implications of methylglyoxal production or detoxification on bacterial pathogenesis and disease progression. (C) 2014 IUBMB Life, 66(10): 667-678, 201

Root mediated uptake of Salmonella is different from phyto-pathogen and associated with the colonization of edible organs

BackgroundPre-harvest contamination of fruits and vegetables by Salmonella in fields is one of the causes of food-borne outbreaks. Natural openings like stomata, hydathodes and fruit cracks are known to serve as entry points. While there are reports indicating that Salmonella colonize and enter root through lateral root emerging area, further investigations regarding how the accessibility of Salmonella to lateral root is different from phyto-pathogenic bacteria, the efficacy of lateral root to facilitate entry have remained unexplored. In this study we attempted to investigate the lateral root mediated entry of Salmonella, and to bridge this gap in knowledge.ResultsUnlike phytopathogens, Salmonella cannot utilize cellulose as the sole carbon source. This negates the fact of active entry by degrading plant cellulose and pectin. Endophytic Salmonella colonization showed a high correlation with number of lateral roots. When given equal opportunity to colonize the plants with high or low lateral roots, Salmonella internalization was found higher in the plants with more lateral roots. However, the epiphytic colonization in both these plants remained unaltered. To understand the ecological significance, we induced lateral root production by increasing soil salinity which made the plants susceptible to Salmonella invasion and the plants showed higher Salmonella burden in the aerial organs.ConclusionSalmonella, being unable to degrade plant cell wall material relies heavily on natural openings. Therefore, its invasion is highly dependent on the number of lateral roots which provides an entry point because of the epidermis remodeling. Thus, when number of lateral root was enhanced by increasing the soil salinity, plants became susceptible to Salmonella invasion in roots and its transmission to aerial organs

Rhizospheric life of Salmonella requires flagella-driven motility and EPS-mediated attachment to organic matter and enables cross-kingdom invasion

Salmonella is an established pathogen of the members of the kingdom Animalia. Reports indicate that the association of Salmonella with fresh, edible plant products occurs at the pre-harvest state, i.e. in the field. In this study, we follow the interaction of Salmonella Typhimurium with the model plant Arabidopsis thaliana to understand the process of migration in soil. Plant factors like root exudates serve as chemo-attractants. Our ex situ experiments allowed us to track Salmonella from its free-living state to the endophytic state. We found that genes encoding two-component systems and proteins producing extracellular polymeric substances are essential for Salmonella to adhere to the soil and roots. To understand the trans-kingdom flow of Salmonella, we fed the contaminated plants to mice and observed that it invades and colonizes liver and spleen. To complete the disease cycle, we re-established the infection in plant by mixing the potting mixture with the fecal matter collected from the diseased animals. Our experiments revealed a cross-kingdom invasion by the pathogen via passage through a murine intermediate, a mechanism for its persistence in the soil and invasion in a non-canonical host. These results form a basis to break the life-cycle of Salmonella before it reaches its animal host and thus reduce Salmonella contamination of food products

A Nanowire-Based Flexible Antibacterial Surface Reduces the Viability of Drug-Resistant Nosocomial Pathogens

The global emergence of antimicrobial resistance poses a serious risk to patients by increasing the cost of healthcare with prolonged stay in hospitals, serious clinical complications, and even death. The ever-increasing challenges in discovering antibacterial agents with novel mechanisms of action necessitates the development of smart antibacterial surfaces that have the potential to minimize colonization of common hospital surfaces with bacterial pathogens. In this work, we report the antibacterial properties of flexible poly­(dimethylsiloxane) (PDMS) polymer decorated with copper hydroxide nanowires (PDMS_Cu) against a panel of drug-resistant bacterial pathogens isolated from patients with bloodstream infection. The fabricated PDMS_Cu surface showed superior antimicrobial activity against both Gram negative (<i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>) and Gram positive (<i>Staphylococcus aureus</i>) bacterial strains as compared to flat PDMS and glass coverslip, which were used as controls. RAW macrophage and HeLa cells were seeded on the PDMS_Cu surface. Their viability was evaluated using confocal microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. PDMS_Cu surface supported the viability of both RAW macrophages and HeLa cells post 5 h of incubation suggesting its potential application in a healthcare setting. Furthermore, we demonstrate the possibility of employing a thin film of PDMS_Cu surface as a protective covering over the microphone of a digital stethoscope to prevent the transmission of nosocomial pathogens between patients. In addition, this fabrication technique was used to coat commercially available gloves with a thin layer of PDMS_Cu, which can be used in a hospital setting to curtail the spread of nosocomial infections while handling infectious instruments and surfaces

A Nanowire-Based Flexible Antibacterial Surface Reduces the Viability of Drug-Resistant Nosocomial Pathogens

The global emergence of antimicrobial resistance poses a serious risk to patients by increasing the cost of healthcare with prolonged stay in hospitals, serious clinical complications, and even death. The ever-increasing challenges in discovering antibacterial agents with novel mechanisms of action necessitates the development of smart antibacterial surfaces that have the potential to minimize colonization of common hospital surfaces with bacterial pathogens. In this work, we report the antibacterial properties of flexible poly­(dimethylsiloxane) (PDMS) polymer decorated with copper hydroxide nanowires (PDMS_Cu) against a panel of drug-resistant bacterial pathogens isolated from patients with bloodstream infection. The fabricated PDMS_Cu surface showed superior antimicrobial activity against both Gram negative (<i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>) and Gram positive (<i>Staphylococcus aureus</i>) bacterial strains as compared to flat PDMS and glass coverslip, which were used as controls. RAW macrophage and HeLa cells were seeded on the PDMS_Cu surface. Their viability was evaluated using confocal microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. PDMS_Cu surface supported the viability of both RAW macrophages and HeLa cells post 5 h of incubation suggesting its potential application in a healthcare setting. Furthermore, we demonstrate the possibility of employing a thin film of PDMS_Cu surface as a protective covering over the microphone of a digital stethoscope to prevent the transmission of nosocomial pathogens between patients. In addition, this fabrication technique was used to coat commercially available gloves with a thin layer of PDMS_Cu, which can be used in a hospital setting to curtail the spread of nosocomial infections while handling infectious instruments and surfaces