Absence of proline-peptide transporter YjiY in Salmonella Typhimurium leads to secretion of factors which inhibits intra-species biofilm formation.

Salmonella is a genus of widely spread Gram negative, facultative anaerobic bacteria, which is known to cause »th of diarrheal morbidity and mortality globally. It causes typhoid fever and gastroenteritis by gaining access to the host gut through contaminated food and water. Salmonella utilizes its biofilm lifestyle to strongly resist antibiotics and persist in the host. Although biofilm removal or dispersal has been studied widely, the inhibition of the initiation of Salmonella Typhimurium (STM WT) biofilm remains elusive. This study demonstrates the anti-biofilm property of the cell-free supernatant obtained from a carbon-starvation induced proline peptide transporter mutant (STM ΔyjiY) strain. The STM ΔyjiY culture supernatant primarily inhibits biofilm initiation by regulating biofilm-associated transcriptional network that is reversed upon complementation (STM ΔyjiY:yjiY). We demonstrate that abundance of FlgM correlates with the absence of flagella in the STM ΔyjiY supernatant treated WT cells. NusG works synergistically with the global transcriptional regulator H-NS. Relatively low abundances of flavoredoxin, glutaredoxin, and thiol peroxidase might lead to accumulation of ROS within the biofilm, and subsequent toxicity in STM ΔyjiY supernatant. This work further suggests that targeting these oxidative stress relieving proteins might be a good choice to reduce Salmonella biofilm.

Topoisomerases in Immune Cell Development and Function.

DNA topoisomerases (TOPs) are complex enzymatic machines with extraordinary capacity to maintain DNA topology during torsion-intensive steps of replication and transcription. Recently, TOPs have gained significant attention for their tissue-specific function, and the vital role of TOPs in immune homeostasis and dysfunction is beginning to emerge. TOPs have been implicated in various immunological disorders such as autoimmunity, B cell immunodeficiencies, and sepsis, underscoring their importance in immune regulation. However, much remains unknown about immunological underpinnings of TOPs, and a deeper understanding of the role of TOPs in the immune system will be critical for yielding significant insights into the etiology of immunological disorders. In this review, we first discuss the recent literature highlighting the contribution of TOPs in the development of immune cells, and we further provide an overview of their importance in immune cell responses.

Pregnancy and Tumour: The Parallels and Differences in Regulatory T Cells.

Immunological tolerance plays a critical role during pregnancy as semi-allogeneic fetus must be protected from immune responses during the gestational period. Regulatory T cells (Tregs), a subpopulation of CD4+ T cells that express transcription factor Foxp3, are central to the maintenance of immunological tolerance and prevention of autoimmunity. Tregs are also known to accumulate at placenta in uterus during pregnancy, and they confer immunological tolerance at maternal-fetal interface by controlling the immune responses against alloantigens. Thus, uterine Tregs help in maintaining an environment conducive for survival of the fetus during gestation, and low frequency or dysfunction of Tregs is associated with recurrent spontaneous abortions and other pregnancy-related complications such as preeclampsia. Interestingly, there are many parallels in the development of placenta and solid tumours, and the tumour microenvironment is considered to be somewhat similar to that at maternal-fetal interface. Moreover, Tregs play a largely similar role in tumour immunity as they do at placenta- they create a tolerogenic system and suppress the immune responses against the cells within tumour and at maternal-fetal interface. In this review, we discuss the role of Tregs in supporting the proper growth of the embryo during pregnancy. We also highlight the similarities and differences between Tregs at maternal-fetal interface and tumour Tregs, in an attempt to draw a comparison between their roles in these two physiologic and pathologic states.