Environmental and genetic modulation of the phenotypic expression of antibiotic resistance

Abstract

Antibiotic resistance can be acquired by mutation or horizontal transfer of a resistance gene, and generally an acquired mechanism results in a predictable increase in phenotypic resistance. However, recent findings suggest that the environment and/or the genetic context can modify the phenotypic expression of specific resistance genes/mutations. An important implication from these findings is that a given genotype does not always result in the expected phenotype. This dissociation of genotype and phenotype has important consequences for clinical bacteriology and for our ability to predict resistance phenotypes from genetics and DNA sequences. A related problem concerns the degree to which the genes/mutations currently identified in vitro can fully explain the in vivo resistance phenotype, or whether there is a significant additional amount of presently unknown mutations/genes (genetic ‘dark matter’) that could contribute to resistance in clinical isolates. Finally, a very important question is whether/how we can identify the genetic features that contribute to making a successful pathogen, and predict why some resistant clones are very successful and spread globally? In this review, we describe different environmental and genetic factors that influence phenotypic expression of antibiotic resistance genes/mutations and how this information is needed to understand why particular resistant clones spread worldwide and to what extent we can use DNA sequences to predict evolutionary success.

Epistatic control of intrinsic resistance by virulence genes in Listeria

“…Gene-gene epistatic interactions are thought to play a critical role in modulating the phenotypic expression of antibiotic resistance and its impact on microbial fitness, and thereby in the evolution of resistance [62–67]. Our findings extend this notion to the relationships between resistance and virulence, two key specific, clinically relevant pathogen traits.…”

Резистентність До Протимікробних Препаратів Серед Клінічних Ізолятів, Виділених При Інфекції Сечових Шляхів У Дітей

“…Результати останніх досліджень де-монструють, що загальноприйняті стандартні та спе-цифічні тести визначення протимікробної чутливості [13-15] є недосконалими [16]. Вони не можуть врахо-вувати різні типи резистентності збудника, зокрема фенотипову резистентність [17,18], визначення якої суттєво змінює картину мінімальної концентрації ан-тибіотика для зупинки росту та гибелі бактерій.…”

Quantitative and synthetic biology approaches to combat bacterial pathogens

“…Sequence-based techniques may not provide sufficient information on drug responses due to the complexity of genotype-phenotype mapping [17,66]. Direct measurements of drug responses may then be preferable.…”

“…Bacterial populations can also collectively survive antibiotic treatments that are lethal to individual cells, leading to collective antibiotic tolerance [13,16]. From an evolutionary perspective, bacteria can gain antibiotic resistance through de novo mutations or horizontal gene transfer, which are processes that are confounded by environmental and genetic context [17]. …”