Ribosome-binding antibiotics increase bacterial longevity and growth efficiency

Area of Science:

• Microbiology
• Bacterial Physiology
• Antibiotic Action

Background:

• Bacteria in real-world environments face fluctuating nutrient availability, impacting population dynamics.
• The interplay between antibiotic treatment, bacterial growth rates, and survival during nutrient stress is not well understood.
• A growth-longevity tradeoff suggests faster growth leads to faster population decline.

Purpose of the Study:

• To investigate how antibiotics, their molecular targets, and resistance mechanisms influence bacterial longevity.
• To determine if bacteriostatic antibiotics that slow growth enhance survival during nutrient-limited conditions.
• To explore the impact of specific resistance mechanisms on the growth-longevity tradeoff.

Main Methods:

• Utilized populations of *Escherichia coli* exposed to various antibiotics.
• Quantified bacterial longevity under different nutrient availability scenarios.
• Examined the effects of ribosome-binding antibiotics (doxycycline, erythromycin) versus those with alternative targets.
• Assessed the impact of ribosomal protection resistance mechanisms on longevity.
• Investigated the role of doxycycline in metabolism and reactive oxygen species (ROS) production.
• Analyzed the correlation between the number of ribosomal RNA operons and bacterial longevity.

Main Results:

• Populations exposed to ribosome-binding antibiotics (doxycycline, erythromycin) exhibited increased longevity during nutrient stress, supporting the growth-longevity tradeoff.
• Antibiotics with alternative cellular targets did not confer the same longevity benefits.
• Ribosomal protection, a resistance mechanism, negated the longevity benefits of doxycycline by restoring growth rates.
• Doxycycline treatment was associated with more efficient metabolism and reduced ROS levels.
• The number of ribosomal RNA operons directly influenced bacterial growth and longevity, even in the absence of antibiotics.

Conclusions:

• Slower bacterial growth, induced by certain antibiotics, can enhance survival during subsequent periods of nutrient stress.
• Ribosomal protection acts as a 'Trojan horse,' offering antibiotic resistance but compromising longevity under nutrient stress.
• Bacterial longevity is influenced by antibiotic type, resistance mechanisms, and intrinsic factors like ribosomal RNA operon copy number.