Bacterial Subcellular Architecture, Structural Epistasis, and Antibiotic Resistance

Abstract

Epistasis refers to the way in which genetic interactions between some genetic loci affect phenotypes and fitness. In this study, we propose the concept of “structural epistasis” to emphasize the role of the variable physical interactions between molecules located in particular spaces inside the bacterial cell in the emergence of novel phenotypes. The architecture of the bacterial cell (typically Gram-negative), which consists of concentrical layers of membranes, particles, and molecules with differing configurations and densities (from the outer membrane to the nucleoid) determines and is in turn determined by the cell shape and size, depending on the growth phases, exposure to toxic conditions, stress responses, and the bacterial environment. Antibiotics change the bacterial cell’s internal molecular topology, producing unexpected interactions among molecules. In contrast, changes in shape and size may alter antibiotic action. The mechanisms of antibiotic resistance (and their vectors, as mobile genetic elements) also influence molecular connectivity in the bacterial cell and can produce unexpected phenotypes, influencing the action of other antimicrobial agents.

Escherichia coli survival in response to ciprofloxacin antibiotic stress correlates with increased nucleoid length and effective misfolded protein management

“…Yet, under a stress induced model of mutagenesis, the lack of bud production at higher antibiotic concentrations may suggest that budding, whilst potentially favourable, is not as closely related to fitness as a reduction in the absolute misfolded protein load. Interestingly, the emergence of such protein damage clearance phenotype in filamentous cells, may support the concept of ‘structural epistasis' recently reviewed by Baquero et al [ 44 ] and may have consequences on antibiotic resistance phenotypes. Further work is needed to fully elucidate the complex misfolded protein dynamics that emerge during bacterial filamentation and specifically with regards to the effect on cellular survival and filamentation.…”

Bdellovibrio’sPrey-Independent Growth is Fuelled by Amino Acids as a Carbon Source

“…This abundance makes the cytoplasm an exceptionally nutrient-rich environment that facilitates the growth of B. bacteriovorus [38,39]. Most of the cytoplasmic proteins are crowded into the vicinity of the cellular envelope, and prey cellular deformation after the bdelloplast formation likely concentrates and increases accessibility to the protein layer [40]. Bdellovibrio proteases can permeate the altered envelope and use these proteins as substrates to obtain small peptides and amino acids.…”

Bacteriostatic cells instead of bacteriostatic antibiotics?

“…The shape can affect the cellular surface/volume ratio, with consequences in the local concentrations of biomolecules and their functional interactions. This phenomenon has been named “structural epistasis” ( 23 ). New organizations in the bacterial subcellular network could produce bacteriostatic cell variants.…”