VariableDNAtopology is an epigenetic generator of physiological heterogeneity in bacterial populations

Abstract

In 1902, Almroth Wright, an Irish-Swedish bacteriologist who had trained in medicine at Trinity College Dublin (TCD), founded the Bacteriology Department at St. Mary's Hospital in London. In 1912, Wright's department provided training in bacteriology for Adrian Stokes, another medical student from TCD, who would become that university's first Professor of Bacteriology and Preventive Medicine in 1919in (Coakley, 1992. Stokes' successor in the TCD chair was Joseph Warwick Bigger, the person who described the phenomenon of "persisters" in bacterial populations (Bigger, 1944). It is believed that Alexander Fleming, working in Wright's department at St. Mary's, was attempting to repeat Bigger's experiments on small colony variants of Staphylococcus aureus (Bigger et al., 1927), when he made the breakthrough in 1928 that led to the discovery of penicillin (Greenwood, 2008). These events illustrate the interconnectedness of institutions, individuals, and ideas in the development of scientific thought.Persisters are bacterial cells that have become non-susceptible to antimicrobial treatment without becoming resistant (Balaban et al., 2019;Bigger, 1944). They are phenotypic outliers with an environment-specific enhanced survival trait, and they arise stochastically in a population of otherwise antimicrobial-susceptible

Transcription-driven DNA supercoiling counteracts H-NS-mediated gene silencing in bacterial chromatin

“…This incomplete commitment results in the coexistence, within the bacterial population, of cells that either express or do not express this program 34 , 63 . Defining the exact role of H-NS in the mechanisms that generate bistability in expression patterns should shed light on the evolutionary dynamics of pathogenicity 64 , 65 .…”

Transcription-driven DNA supercoiling activates bacterial chromatin at a distance

“…This incomplete commitment results in the coexistence, within the bacterial population, of cells that either express or do not express this program 32,60 . Defining the exact role of H-NS in the mechanisms that generate bistability in expression patterns should shed light on the evolutionary dynamics of pathogenicity 61,62 .…”

Transcription activation in Escherichia coli and Salmonella

“…This comforting view dominates the literature, and yet it may not be the whole story since we know that, within bacterial populations, especially during infections, there is cell-to-cell variation in the expression of certain gene products, and this variation may ensure the survival of some in really hostile environments, such as a mammalian host. Whilst there are several possible sources of such variation (128,129), one involves transcription activators, whose activity may not be coupled to any effector, but, rather, is subject to random cell-to-cell variation.…”