Mixed species biofilm: Structure, challenge and its intricate involvement in hospital associated infections.

Hospital associated infections or healthcare associated infections (HAIs) are a major threat to healthcare and medical management, mostly because of their recalcitrant nature. The primary cause of these HAIs is bacterial associations, especially the interspecies interactions. In interspecies interactions, more than one species co-exists in a common platform of extracellular polymeric substances (EPS), establishing a strong interspecies crosstalk and thereby lead to the formation of mixed species biofilms. In this process, the internal microenvironment and the surrounding EPS matrix of the biofilms ensure the protection of the microorganisms and allow them to survive under antagonistic conditions. The communications between the biofilm members as well as the interactions between the bacterial cells and the matrix polymers, also aid in the rigidity of the biofilm structure and allow the microorganisms to evade both the host immune response and a wide range of anti-microbials. Therefore, to design a treatment protocol for HAIs is difficult and it has become a growing point of concern. This review therefore first aims to discuss the role of microenvironment, molecular structure, cell-cell communication, and metabolism of mixed species biofilms in manifestation of HAIs. In addition, we discuss the electrochemical properties of mixed-species biofilms and their mechanism in developing drug resistance. Then we focus on the most dreaded bacterial HAI including oral and gut multi-species infections, catheter-associated urinary tract infections, surgical site infections, and ventilator-associated pneumonia. Further, we highlight the challenges to eradication of the mixed species biofilms and the current and prospective future strategies for the treatment of mixed species-associated HAI. Together, the review presents a comprehensive understanding of mixed species biofilm-mediated infections in clinical scenario, and summarizes the current challenge and prospect of therapeutic strategies against HAI.

The strategic involvement of IRS in cancer progression.

Insulin Receptor Substrate (IRS), an intracellular molecule devoid of an intrinsic kinase activity, is activated upon binding to IR which thereby works as a scaffold, organizing all signaling complexes and initiating the signaling process downstream. The level of IRS proteins and their stability in the cell is mostly maintained through the phosphorylation status of their tyrosine and serine residues. IRS is positively regulated by phosphorylation of its Tyr residues whereas a Ser residue phosphorylation attenuates it, although there exist some exceptions as well. Other post-translational modifications like O-linked glycosylation, N-linked glycosylation and acetylation also play a prominent role in IRS regulation. Since the discovery of the Warburg effect, people have been curious to find out all possible signaling networks and molecules that could lead to cancer and no doubt, the insulin signaling pathway is identified as one such pathway, which is highly deregulated in cancers. Eminent studies reveal that IRS is a pertinent regulator of cancer and is highly overexpressed in the five most commonly occurring cancers namely- Prostate, Ovarian, Breast, Colon and Lung cancers. IRS1 and IRS2 family members are actively involved in the progression, invasion and metastasis of these cancers. Recently, less studied IRS4 has also emerged as a contributor in ovarian, breast, colorectal and lung cancer, but no such studies related to IRS4 are found in Prostate cancer. The involvement of other IRS family members in cancer is still undiscovered and so paves the way for further exploration. This review is a time-lapse study of IRSs in the context of cancer done over the past two decades and it highlights all the major discoveries made till date, in these cancers from the perspective of IRS.

Caveolin-1 and lipids: Association and their dualism in oncogenic regulation.

Caveolin-1 (Cav-1) is a structural protein of caveolae that functions as a molecular organizer for different cellular functions including endocytosis and cellular signaling. Cancer cells take advantage of the physical position of Cav-1, as it can communicate with extracellular matrix, help to organize growth factor receptors, redistribute cholesterol and glycosphingolipids, and finally transduce signals within the cells for oncogenesis. Recent studies emphasize the exceeding involvement of Cav-1 with different lipid bodies and in altering the metabolism, especially lipid metabolism. However, the association of Cav-1 with different lipid bodies like lipid rafts, lipid droplets, cholesterols, sphingolipids, and fatty acids is remarkably dynamic. The lipid-Cav-1 alliance plays a dual role in carcinogenesis. Both cancer progression and regression are modified and affected by the type of lipid molecule's association with Cav-1. Accordingly, this Cav-1-lipid cooperation exemplifies a cancer-type-specific treatment strategy for a better prognosis of the disease. In this review, we first present Cav-1 as an oncogenic molecule and its communication via lipid raft. We discussed the involvement of Cav-1 with lipid droplets, Cholesterol, sphingolipids, gangliosides, and ceramides. Further, we describe the Cav-1-mediated altered Fatty acid metabolism in cancer and the strategic therapeutic approaches toward Cav-1 targeting.