Mycobacterium tuberculosis(Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. The current treatment regime is long and expensive, and missed doses contribute to drug resistance. Therefore, development of new anti-TB drugs remains one of the highest public health priorities.Mtbhas evolved a complex cell envelope that represents a formidable barrier to antibiotics. TheMtbcell envelop consists of four distinct layers enriched forMtbspecific lipids and glycans. Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. TheMtbplasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. However, the role of PIMs in the structure and function of the membrane remains elusive. Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. We assess both symmetric and asymmetric assemblies of theMtbplasma membrane and compare this with residue distributions ofMtbintegral membrane protein structures. To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. This paves the way for future studies on antibiotic development and understandingMtbmembrane protein function.

In most cases, inverse type diarylethenes (DAEs) exhibit a bathochromic shift of the π-conjugation absorption band after photocyclization, which leads to “visible” closed forms and “visible” photochromic behaviors. The reason for the bathochromic shift is that the lone pair electrons on the sulfur atoms of the thiophene rings function as π-electrons and participate in π-conjugation. To make photochromic behaviors “invisible”, electron-withdrawing aldehyde groups were introduced into the inverse DAE to endow lone pair electrons on the sulfur atoms with more n-electron characteristics and then achieved the hypsochromic shift of the π-conjugation absorption band after photocyclization. As a result, the absorption changes of aldehyde modified inverse DAE (IDAEo-2CHO) remained “invisible” during isomerization, and the only fluorescence changes can be observed by the naked eye after photocyclization. Taking advantage of this unique optical feature of IDAEo-2CHO, anti-counterfeiting applications were implemented.