6
1 Antibacterials
1.3 Bacterial Resistance to Antibacterials
1.3.1 Introduction to Key Resistance Mechanisms
A number of molecular mechanisms have evolved in bacteria to combat exposure to
antibacterial agents and these are covered in detailed reviews by Blair et al. (2015) and
Munita and Arias (2016). The mechanisms fall into a number of general categories
including the expression of multiple types of efflux pumps to export antibacterials and
reduce their intracellular concentrations to sub-lethal levels; alteration of biological
target structures or increased expression of such targets; changes in metabolism and
metabolic activity; sporulation; and biofilm formation.
Biologically, the types of resistance are characterised as intrinsic, acquired or
adaptive. Intrinsic resistance is defined as the inherent ability of an individual species
of bacterium, as a result of its structural or functional properties, to resist the action
of an antibiotic or antibacterial agent. This may occur because of a lack of the target
of the antibiotic or through barriers to permeation for example. In contrast, acquired
resistance involves the bacterium picking up or acquiring resistance elements for
counteracting particular antibiotics. These elements may include ways to minimize
the intracellular concentration of the antibiotic, modification of the antibiotic target
site, or chemical modification of the antibiotic to negate its activity (Blair et al. 2014).
Adaptive resistance is characterised by the temporary acquisition of resistance
elements in response to external threats as could be the case on exposure to an antibiotic (Gorityala et al. 2016). In nature, antibiotics have a number of different roles and
the way antibiotic resistance is developed in the natural environment is important
when considering which mechanisms transfer to human pathogenic bacteria. Natural
antibiotics or antibacterials from non-human sources are thought to have evolved to
control competitive bacteria in the soil and aquatic environment. The human microbiome does, however, produce antimicrobial agents for bacterial competitors and
these can display activity against some human pathogenic bacteria like Clostridium
difficile, which is now named as Clostridioides difficile as noted by the Centers for
Disease Control and Prevention in the USA (CDC 2019). Both taxonomic names for
this species are used in this book reflecting the name used in the original sources.
For a comprehensive multi-authored set of reviews in this general resistance area see
Walsh (2015).
New agents which can block or attenuate antibiotic resistance would be of great
interest in the fight against bacterial resistance. Recent work on slowing such antibiotic resistance by an anti-oxidant (Edaravone) in the presence of the antibacterial
ciprofloxacin in pathogenic Escherichia coli is of considerable significance in this
connection and points to the possible further development of small molecules to
block the evolutionary development of resistance (anti-evolvability drugs) (Pribis
et al. 2019).
1 Antibacterials
1.3 Bacterial Resistance to Antibacterials
1.3.1 Introduction to Key Resistance Mechanisms
A number of molecular mechanisms have evolved in bacteria to combat exposure to
antibacterial agents and these are covered in detailed reviews by Blair et al. (2015) and
Munita and Arias (2016). The mechanisms fall into a number of general categories
including the expression of multiple types of efflux pumps to export antibacterials and
reduce their intracellular concentrations to sub-lethal levels; alteration of biological
target structures or increased expression of such targets; changes in metabolism and
metabolic activity; sporulation; and biofilm formation.
Biologically, the types of resistance are characterised as intrinsic, acquired or
adaptive. Intrinsic resistance is defined as the inherent ability of an individual species
of bacterium, as a result of its structural or functional properties, to resist the action
of an antibiotic or antibacterial agent. This may occur because of a lack of the target
of the antibiotic or through barriers to permeation for example. In contrast, acquired
resistance involves the bacterium picking up or acquiring resistance elements for
counteracting particular antibiotics. These elements may include ways to minimize
the intracellular concentration of the antibiotic, modification of the antibiotic target
site, or chemical modification of the antibiotic to negate its activity (Blair et al. 2014).
Adaptive resistance is characterised by the temporary acquisition of resistance
elements in response to external threats as could be the case on exposure to an antibiotic (Gorityala et al. 2016). In nature, antibiotics have a number of different roles and
the way antibiotic resistance is developed in the natural environment is important
when considering which mechanisms transfer to human pathogenic bacteria. Natural
antibiotics or antibacterials from non-human sources are thought to have evolved to
control competitive bacteria in the soil and aquatic environment. The human microbiome does, however, produce antimicrobial agents for bacterial competitors and
these can display activity against some human pathogenic bacteria like Clostridium
difficile, which is now named as Clostridioides difficile as noted by the Centers for
Disease Control and Prevention in the USA (CDC 2019). Both taxonomic names for
this species are used in this book reflecting the name used in the original sources.
For a comprehensive multi-authored set of reviews in this general resistance area see
Walsh (2015).
New agents which can block or attenuate antibiotic resistance would be of great
interest in the fight against bacterial resistance. Recent work on slowing such antibiotic resistance by an anti-oxidant (Edaravone) in the presence of the antibacterial
ciprofloxacin in pathogenic Escherichia coli is of considerable significance in this
connection and points to the possible further development of small molecules to
block the evolutionary development of resistance (anti-evolvability drugs) (Pribis
et al. 2019).