Functional redundancy and plasticity in staphylococcus aureus vitamin B1 metabolism ensure stable colonisation in the environment and in the host

In this study, we explored fastidious metabolic pathways of Staphylococcus aureus and showed that the organism is auxotrophic for thiamine. Thiamine plays a key role in carbohydrate metabolism and is essential for ATP synthesis in both prokaryotes and eukaryotes. We demonstrated that thiamine deprivation is lethal in S. aureus and explored the essential pathway involved in vitamin biosynthesis and transport. Moreover, we have shown that thiVWX is a thiamine, TMP, and TPP transporter instead of a previously hypothesized HMP (thiamine precursor) transporter. Lastly, we also showed how the S. aureus thiamine pathway redundancy is necessary for S. aureus survival in different environmental niches. With multi-drug resistant (MDR) pathogen becoming a global issue and the lack of new drug discovery, our results open up new revenue for developing drugs against the MDR pathogen.Doctor of Philosoph

Experiments for understanding pedestrian dynamics

Conference Proceedings - European Microwave Conference2201371-1376CEMC

Role of complex modes in coplanar-waveguide-to-coplanar-waveguide discontinuity calculations

Microwave and Optical Technology Letters49-MOTL

Adversity quotient : the effects of environment and personality.

A study on the effects of environment and personality on the Adversity Quotient scores of MBA students and Final Year Students of NT

Effectiveness of procreation tax incentives on the fertility decision in Singapore

Evaluating the effectiveness of procreation tax incentives and other relevant factors on the fertility decision, that is the decision to have a child

Comparative phenotypic and transcriptomic analyses unravel conserved and distinct mechanisms underlying shade avoidance syndrome in Brassicaceae vegetables

10.1186/s12864-021-08076-1BMC Genomics22176

Oncologic efficacy is not compromised, and may be improved with minimally invasive esophagectomy.

BACKGROUND: Major morbidity and mortality rates continue to be high in large series of transthoracic esophagectomies. Minimally invasive approaches are being increasingly used. We compare our growing series of minimally invasive (combined thoracoscopic and laparoscopic) esophagectomies (MIEs) with a series of open transthoracic esophagectomies. STUDY DESIGN: We identified 65 patients who underwent an MIE with thoracoscopy/laparotomy (n = 11), Ivor Lewis (n = 2), or 3-hole approach (n = 52). These patients were compared with 53 patients who underwent open Ivor-Lewis esophagectomy (n = 15) or 3-hole esophagectomy (n = 38) over the past 10 years. RESULTS: The MIE and open groups were similar regarding gender and average age. The majority of patients in the open group underwent neoadjuvant chemoradiation therapy (81%); a significantly smaller (43%) number of patients in the MIE group underwent neoadjuvant therapy (p \u3c 0.0001). Regarding oncologic efficacy, 97% and 94% of patients in both groups underwent R0 resections. Patients undergoing MIE had a significant increase in the number of harvested lymph nodes (median 20 vs 9; p \u3c 0.0001). Length of stay was significantly decreased in patients who underwent MIE (8.5 days vs 16 days; p = 0.002). Finally, there were significantly fewer serious complications (grades 3-5) in the MIE group (19% vs 48%; p = 0.0008). CONCLUSIONS: In this initial report of a single-institution series of MIE, we demonstrate that oncologic efficacy is not compromised and may actually be improved with a significantly increased number of harvested LNs. We also demonstrate that this approach is associated with fewer serious complications and a significant decrease in the length of postoperative hospital stay

Adaptation to an Amoeba Host Leads to Pseudomonas aeruginosa Isolates with Attenuated Virulence

The opportunistic pathogen Pseudomonas aeruginosa is ubiquitous in the environment, and in humans, it is capable of causing acute or chronic infections. In the natural environment, predation by bacterivorous protozoa represents a primary threat to bacteria. Here, we determined the impact of long-term exposure of P. aeruginosa to predation pressure. P. aeruginosa persisted when coincubated with the bacterivorous Acanthamoeba castellanii for extended periods and produced genetic and phenotypic variants. Sequencing of late-stage amoeba-adapted P. aeruginosa isolates demonstrated single nucleotide polymorphisms within genes that encode known virulence factors, and this correlated with a reduction in expression of virulence traits. Virulence for the nematode Caenorhabditis elegans was attenuated in late-stage amoeba-adapted P. aeruginosa compared to early-stage amoeba-adapted and nonadapted counterparts. Further, late-stage amoeba-adapted P. aeruginosa showed increased competitive fitness and enhanced survival in amoebae as well as in macrophage and neutrophils. Interestingly, our findings indicate that the selection imposed by amoebae resulted in P. aeruginosa isolates with reduced virulence and enhanced fitness, similar to those recovered from chronic cystic fibrosis infections. Thus, predation by protozoa and long-term colonization of the human host may represent similar environments that select for similar losses of gene function. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute infections in plants and animals, including humans, and chronic infections in immunocompromised and cystic fibrosis patients. This bacterium is commonly found in soils and water, where bacteria are constantly under threat of being consumed by bacterial predators, e.g., protozoa. To escape being killed, bacteria have evolved a suite of mechanisms that protect them from being consumed or digested. Here, we examined the effect of long-term predation on the genotypes and phenotypes expressed by P. aeruginosa. We show that long-term coincubation with protozoa gave rise to mutations that resulted in P. aeruginosa becoming less pathogenic. This is particularly interesting as similar mutations arise in bacteria associated with chronic infections. Importantly, the genetic and phenotypic traits possessed by late-stage amoeba-adapted P. aeruginosa are similar to those observed in isolates obtained from chronic cystic fibrosis infections. This notable overlap in adaptation to different host types suggests similar selection pressures among host cell types as well as similar adaptation strategies