Bacterial responses to antibiotics and their combinations

Abstract

Antibiotics affect bacterial cell physiology at many levels. Rather than just compensating for the direct cellular defects caused by the drug, bacteria respond to antibiotics by changing their morphology, macromolecular composition, metabolism, gene expression and possibly even their mutation rate. Inevitably, these processes affect each other, resulting in a complex response with changes in the expression of numerous genes. Genome-wide approaches can thus help in gaining a comprehensive understanding of bacterial responses to antibiotics. In addition, a combination of experimental and theoretical approaches is needed for identifying general principles that underlie these responses. Here, we review recent progress in our understanding of bacterial responses to antibiotics and their combinations, focusing on effects at the levels of growth rate and gene expression. We concentrate on studies performed in controlled laboratory conditions, which combine promising experimental techniques with quantitative data analysis and mathematical modeling. While these basic research approaches are not immediately applicable in the clinic, uncovering the principles and mechanisms underlying bacterial responses to antibiotics may, in the long term, contribute to the development of new treatment strategies to cope with and prevent the rise of resistant pathogenic bacteria.

Mechanistic origin of drug interactions between translation-inhibiting antibiotics

“…Recently, mechanism-independent mathematical approaches to predict the responses to multi-drug combinations were proposed [Zimmer et al , 2016; Wood et al , 2012], yet these approaches rely on prior knowledge of pairwise drug interactions, which are diverse and have notoriously resisted prediction. They include synergism (inhibition is stronger than predicted), antagonism (inhibition is weaker), and suppression (one of the drugs loses potency) [Bollenbach, 2015; Mitosch and Bollenbach, 2014] (Fig. 1C).…”

Ecotoxicological assessment of antibiotics: A call for improved consideration of microorganisms

“…Antibiotics usually do not occur as isolated, pure chemicals in the environment, but as complex chemical mixtures. The environmental assessment of antibiotic mixtures has been discussed in a series of recent papers (Altenburger et al, 2012;Altenburger et al, 2015;Backhaus, 2014;Mitosch and Bollenbach, 2014), and is therefore not a specific subject of the present analysis. This manuscript was conceived at a workshop on antibiotics and antibiotic resistance in the environment and it focuses on ecotoxicological aspects, whereas other reviews and opinion papers conceived at the same workshop deal with other aspects of antibiotics and antibiotic resistance in the environment (Ashbolt et al, 2013;Finley et al, 2013;Gaze et al, 2013;Pruden et al, 2013).…”

Sublethal Concentrations of Antibiotics Cause Shift to Anaerobic Metabolism in Listeria monocytogenes and Induce Phenotypes Linked to Antibiotic Tolerance

“…Besides being a human pathogen, L. monocytogenes is also a saprophyte with a natural habitat in decaying plant material ( Cossart, 2011 ). Whilst the bacterium is exposed to lethal concentrations of antibiotics during listeriosis treatment, it will likely be exposed to a window of antibiotic concentrations including low and sublethal concentrations both in the host ( Hof et al, 1997 ) as well as in its saprophytic lifestyle due to co-existence with antibiotic-producing microorganisms ( Andersson and Hughes, 2014 ; Mitosch and Bollenbach, 2014 ) and even extremely low antibiotic concentrations can select for maintenance of multi-resistance plasmids and resistant bacteria ( Gullberg et al, 2011 , 2014 ).…”