Richards Lancaster (iceanger27)

Early childhood caries is a severe oral disease that results in aggressive tooth decay. Particularly, a synergistic association between a fungus, Candida albicans, and a cariogenic bacterium, Streptococcus mutans, promotes the development of hard-to-remove and highly acidic biofilms, exacerbating the virulent damage. These interactions are largely mediated via glucosyltransferases (GtfB) binding to mannans on the cell wall of C. albicans Here, we present an enzymatic approach to target GtfB-mannan interactions in this cross-kingdom consortium using mannan-degrading exo- and endo-enzymes. These exo- and endo-enzymes are highly effective in reducing biofilm biomass without killing microorganisms, as well as alleviating the production of an acidic pH environment conducive to tooth decay. To corroborate these results, we present biophysical evidence using single-molecule atomic force microscopy, biofilm shearing, and enamel surface topography analyses. Data show a drastic decrease in binding forces of GtfB to C. nduce the prevalence of drug resistance over time. By specifically targeting the interaction mechanism whereby mannoproteins on the C. albicans surface mediate the cross-kingdom interaction, we demonstrated that mannoprotein-degrading enzymes can effectively disrupt biofilm interactions without microbiocidal effects or causing cytotoxicity to human cells. This suggests a potential application as a targeted approach for intervening a pathogenic cross-kingdom biofilm associated with a costly and unresolved oral disease.Mycobacterium abscessus (Mab) is an emerging pathogen that is highly tolerant to current antibiotic therapies, and the current standard of care has a high failure rate. Mycobacteriophages represent a promising alternative treatment that have the potential to kill Mab with few side effects. However, the repertoire of phages that infect Mab is limited, and little is understood about the determinants of phage susceptibility in mycobacteria. Two studies from the Hatfull group (R. M. Dedrick, B. E. Smith, R. A. Garlena, D. A. Russell, et al., mBio 12e03431-20, 2021, https//doi.org/10.1128/mBio.03431-20, and R. M. Dedrick, H. G. Aull, D. Jacobs-Sera, R. A. Garlena, et al., mBio 12e03441-20, 2021, https//doi.org/10.1128/mBio.03441-20) shed new light on the natural phage complement of Mab and provide some of the first insights into what factors might drive susceptibility to these phages. These studies not only lay the groundwork for therapeutic development of more effective phage therapy in Mab but also provide a foothold for studying how mobile elements such as phages and plasmids impact Mab biology and evolution.Genomic information from various magnetotactic bacteria suggested that besides their common ability to form magnetosomes, they potentially also represent a source of bioactive natural products. By using targeted deletion and transcriptional activation, we connected a large biosynthetic gene cluster (BGC) of the trans-acyltransferase polyketide synthase (trans-AT PKS) type to the biosynthesis of a novel polyketide in the alphaproteobacterium Magnetospirillum gryphiswaldense Structure elucidation by mass spectrometry and nuclear magnetic resonance spectroscopy (NMR) revealed that this secondary metabolite resembles sesbanimides, which were very recently reported from other taxa. However, sesbanimide R exhibits an additional arginine moiety the presence of which reconciles inconsistencies in the previously proposed sesbanimide biosynthesis pathway observed when comparing the chemical structure and the potential biochemistry encoded in the BGC. In contrast to the case with sesbanimides D, E, and F, we were able to assign the stereocenter of the arginine moiety experimentally and two of the remaining three stereocenters by predictive biosynthetic tools. Sesbanimide R displayed strong cytotoxic activity against several carcinoma cell lines.IMPORTANCE The findings of this study contribute a new secondary metaboli