This review will focus on strategies to develop new treatments that target the biofilm mode of growth and that can be used to treat biofilm infections. These approaches aim to reduce or inhibit biofilm formation, or to increase biofilm dispersion. Many antibiofilm compounds are not bactericidal but render the cells in a planktonic growth state, which are more susceptible to antibiotics and more easily cleared by the immune system. Novel compounds are being developed with antibiofilm activity that includes antimicrobial peptides, natural products, small molecules and polymers. Bacteriophages are being considered for use in treating biofilms, as well as the use of enzymes that degrade the extracellular matrix polymers to dissolve biofilms. There is great potential in these new approaches for use in treating chronic biofilm infections.

word count: 216 21 Text word count: 8953 (Methods section is 3400) 22 Abstract 23Gut microbiomes make major contributions to the physiological and immunological 24 development of the host, but the relative importance of their bacterial and fungal components, 25 and how they interact, remain largely unknown. We applied carefully controlled experiments in 26 gnotobiotic mice colonized with defined communities of bacteria, fungi, or both to differentiate 27 the direct role of fungi on microbiome assembly, host development, and susceptibility to colitis 28 and airway inflammation. Our results revealed that fungal colonization alone was insufficient to 29 promote the intestinal anatomic and physiological changes seen in mice colonized by bacteria, 30 and had limited impact on the fecal metabolome. However, fungal colonization promoted major 31 shifts in bacterial microbiome ecology, and had an independent effect on the innate and adaptive 32 immune development in young mice. Fungi further exacerbated some aspects of the 33 inflammatory effects of the bacterial community during OVA-induced airway inflammation by 34 promoting macrophage infiltration in the airway. Our results demonstrate a dominant ecological 35 and physiological role of bacteria in gut microbiomes, but highlight fungi as an ecological factor 36 shaping the assembly of the bacterial community and a direct capacity to impact immune system 37 and modulate disease susceptibility. These findings demonstrate that studies focused on bacteria 38 alone provide an incomplete portrayal on microbiome ecology and functionality, and prompt for 39 the inclusion of fungi in human microbiome studies. 40 41 42 43 44 45 65 suggestive of fungal overgrowth by this common yeast18. As well, another common yeast, 66 Malassezia restricta, was present in the majority of patients carrying the IBD risk allele CARD9, 67 a molecule involved in fungal innate immunity19. Experimental colonization of mice with M. 68 4 restricta resulted in exacerbated Dextran Sodium Sulfate (DSS)-induced colitis, characterized by 69 CARD9-dependent Th1 and Th17 inflammation19. 70Early-life gut dysbiosis has also been linked to atopic asthma. We had previously shown 71 that early-life bacterial communities are altered in Canadian infants that later developed atopic-72 wheeze20. Fujimura et al. extended our findings and revealed an expansion of Candida sp. and 73 Rhodotorula sp. in stool samples from US infants that later developed atopy13. Similarly, we 74 detected mycobiome alterations in stool of rural Ecuadorian infants that developed atopic-75 wheeze at 5 years12. Differences in the fungal community were more strongly associated with 76 asthma risk than bacterial dysbiosis in the Ecuadorian study, in which we detected an 77 overrepresentation of total fungal sequences and an expansion of the yeast Pichia kudriavzevii in 78 children who later developed symptoms12. While these studies revealed interesting associations 79 between early-life mycobiome alterations and infant atopy and asthma, the causal...