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.