Mini Review: Bacterial Membrane Composition and Its Modulation in Response to Stress

Abstract

Antibiotics and other agents that perturb the synthesis or integrity of the bacterial cell envelope trigger compensatory stress responses. Focusing on Bacillus subtilis as a model system, this mini-review summarizes current views of membrane structure and insights into how cell envelope stress responses remodel and protect the membrane. Altering the composition and properties of the membrane and its associated proteome can protect cells against detergents, antimicrobial peptides, and pore-forming compounds while also, indirectly, contributing to resistance against compounds that affect cell wall synthesis. Many of these regulatory responses are broadly conserved, even where the details of regulation may differ, and can be important in the emergence of antibiotic resistance in clinical settings.

Lipid-mediated antimicrobial resistance: a phantom menace or a new hope?

“…Gram-positive bacteria also possess methods for enzymatic modification of lipids to modulate membrane surface charge. For example, they can reduce CAMP susceptibility by increasing production of cationic lysyl-PG, which lessens interactions with cationic antimicrobials by increasing electrostatic repulsion (Willdigg and Helmann 2021 ). In particular, the MprF system, which catalyses the aminoacyl-tRNA-dependent lysylation of PG to lysyl-PG, also acts as a flippase (Ernst and Peschel 2011 ), translocating lysl-PG from the inner to the outer leaflet, which reduces the overall negative membrane surface charge and provides protection against CAMPs (Andrä et al 2011 ; Mishra et al 2011 ; Kumariya et al 2015 ; Ernst et al 2018 ; Sabat et al 2018 ; Ernst and Peschel 2019 ).…”

“…Bacterial membranes are dynamic and heterogenous assemblies of macromolecules that contain lipids, proteins and glycans, and act as the primary physical barrier for the cell entry of antimicrobial agents (Strahl and Errington 2017 ; May and Grabowicz 2018 ; Willdigg and Helmann 2021 ). Consequently, membrane-active antimicrobial agents which target the bacterial membrane, either by disrupting the functional integrity of the bacterial membrane itself or modulating the function of essential membrane-associated proteins, can greatly hinder bacterial viability (Zasloff 2002 ; Fjell et al 2012 ; Mingeot-Leclercq and Décout 2016 ).…”

How Does the Spatial Confinement of FtsZ to a Membrane Surface Affect Its Polymerization Properties and Function?

“…Therefore, membrane composition also plays a regulatory role in cell physiology. Stress is known to trigger metabolic pathways that sense threats and mount a protective response involving modification of cell wall composition through the regulation of biosynthetic pathways of their components ( Rowlett et al, 2017 ; Willdigg and Helmann, 2021 ). There is evidence that certain lipids are enriched in the division site ( Mileykovskaya and Dowhan, 2005 ), indicating that the division process is no exception.…”

An Stomatin, Prohibitin, Flotillin, and HflK/C-Domain Protein Required to Link the Phage-Shock Protein to the Membrane in Bacillus subtilis

“…Organization and surveillance of plasma membrane integrity is of vital importance for cellular life. Hence, several systems have been described that are part of membrane organization, stress perception and membrane repair (Willdigg and Helmann, 2021). Many of the involved proteins are ubiquitously distributed in all domains of life.…”

“…Many of the involved proteins are ubiquitously distributed in all domains of life. One of the protein families that is widely distributed are the SPFH-domain proteins (Langhorst et al, 2005;Browman et al, 2007;Willdigg and Helmann, 2021). Among these proteins are flotillins, proteins that have been attributed with functional membrane domains in proand eukaryotes (Stuermer and Plattner, 2005;Bramkamp and Lopez, 2015).…”