Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution

Area of Science:

• Microbiology
• Genetics
• Pharmacology

Background:

• Traditional antibiotic response classification is binary (sensitive/resistant).
• Evidence shows bacterial antibiotic responses are highly heterogeneous.
• This heterogeneity contributes to antibiotic treatment failure.

Purpose of the Study:

• To review mechanisms causing heterogeneous antibiotic responses in bacteria.
• To discuss how mutations influence bacterial population dynamics under antibiotic pressure.
• To highlight future research directions in noncanonical antibiotic phenotypes.

Main Methods:

• Literature review focusing on genome maintenance, transcription, and translation.
• Analysis of within-host evolution and its impact on bacterial regulatory networks.
• Synthesis of current knowledge on antibiotic persistence, tolerance, heteroresistance, resilience, and perseverance.

Main Results:

• Noncanonical antibiotic phenotypes (persistence, tolerance, etc.) are widespread.
• Mechanisms in genome maintenance, transcription, and translation drive heterogeneity.
• Within-host mutations can alter regulatory stochasticity, favoring bacterial propagation.

Conclusions:

• Bacterial antibiotic responses exhibit significant heterogeneity beyond sensitivity/resistance.
• Understanding these noncanonical phenotypes is crucial for combating treatment failure.
• Further research into underlying mechanisms and evolutionary dynamics is warranted.