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Effects of subminimum inhibitory concentrations of antibiotics on the Pasteurella multocida proteome
Bindu Nanduri1, Mark L Lawrence, Carolyn R Boyle
1College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762, USA.
Abstract:
Subminimum inhibitory concentrations (sub-MICs) of antibiotics can be therapeutically effective, but the underlying molecular mechanisms are not well-characterized. We analyzed the Pasteurella multocida proteome response to sub-MICs of amoxicillin, chlortetracycline, and enrofloxacin using isotope-coded affinity tags (ICAT). There were parallel effects on inhibition of growth kinetics and suppression of protein expression by clusters of orthologous groups (COG) categories. Potential compensatory mechanisms enabling antibiotic adaptation were identified, including increased RecA expression caused by enrofloxacin.
Insights
Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics can be effective, but mechanisms are unclear. This study reveals how sub-MIC antibiotic treatments alter Pasteurella multocida protein expression and identifies adaptive responses.
Area of Science:
- Microbiology
- Proteomics
- Pharmacology
Background:
- Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics can exert therapeutic effects, yet the molecular underpinnings remain poorly understood.
- Understanding these mechanisms is crucial for optimizing antibiotic therapy and combating resistance.
Purpose of the Study:
- To investigate the proteome response of Pasteurella multocida to sub-MICs of amoxicillin, chlortetracycline, and enrofloxacin.
- To identify potential molecular mechanisms and compensatory strategies employed by bacteria under sub-inhibitory antibiotic stress.
Main Methods:
- Utilized isotope-coded affinity tags (ICAT) to perform a comprehensive proteomic analysis.
- Quantified changes in protein expression in response to different sub-MIC antibiotic treatments.
- Analyzed protein expression patterns in relation to Clusters of Orthologous Groups (COG) categories.
Main Results:
- Observed parallel effects of sub-MIC antibiotics on growth kinetics inhibition and protein expression suppression across COG categories.
- Identified specific protein expression alterations induced by amoxicillin, chlortetracycline, and enrofloxacin.
- Discovered potential bacterial adaptation mechanisms, such as increased RecA expression in response to enrofloxacin.
Conclusions:
- Sub-MIC antibiotic exposure significantly impacts bacterial proteomes, affecting growth and protein expression.
- The proteomic response provides insights into bacterial adaptation strategies under sub-inhibitory antibiotic pressure.
- Enrofloxacin, at sub-MICs, can induce adaptive responses like increased RecA expression in Pasteurella multocida.
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