@article{mbs:/content/journal/acmi/10.1099/acmi.mim2019.po0006, author = "Halkerston, Rachel and Davies, Katherine and Tolley, Howard and Keating, Thomas and Taylor, Stephen and Alderwick, Luke and Bacon, Joanna", title = "The role of mature mycolic acids in mycobacterial biofilm formation and interactions with the human complement system", journal= "Access Microbiology", year = "2020", volume = "2", number = "1", pages = "", doi = "https://doi.org/10.1099/acmi.mim2019.po0006", url = "https://www.microbiologyresearch.org/content/journal/acmi/10.1099/acmi.mim2019.po0006", publisher = "Microbiology Society", issn = "2516-8290", type = "Journal Article", eid = "38", abstract = "Tuberculosis, causative agent Mycobacterium tuberculosis, caused an estimated 10 million new cases and 1.6 million deaths in 2017. Mycobacterial cell wall components are important for host-pathogen interactions and modulating the innate and adaptive immune response. Much is understood about the interplay between bacterial phenotype, cell wall modulation and interaction with aspects of the immune response. However, the impact of phenotype, such as biofilms on complement system activation, has not been studied in-depth. M. tuberculosis may persist as biofilms in a chronic, non-replicating state. Mycolic acids are a major cell wall lipid and their accumulation is a hallmark of biofilm formation. M. smegmatis was mutated in gene MSMEG4722(orthologof M. tuberculosis Rv2509) (ΔMSMEG4722)which encodes a reductase involved in the final step of mycolic acid biosynthesis. Using ΔMSMEG4722,this project explored the role of mycolic acid maturation in biofilm development, determined the relationship between lipids and complement activity with planktonic or biofilm bacteria. Thin-layer chromatography of ΔMSMEG4722 biofilms displayed a loss of mature free mycolic acid compared to M. smegmatis, but accumulated un-reduced free mycolate. In both biofilm and planktonicΔMSMEG4722, distribution of the virulence factor trehalose dimycolate changed throughout the cell wall compared to M. smegmatis. Flow cytometry analysis of the deposition of complement opsonin C3b revealed increased C3 on planktonic ΔMSMEG4722 compared to M. smegmatis, but this difference was not observed on bacteria from biofilms. Evidence from this work suggests mycolic acid maturation is important for biofilm development and plays a role in complement activation on mycobacteria.", }