What Is the Impact of Antibiotic Resistance Determinants on the Bacterial Death Rate?

TL;DR

This study explores how antibiotic resistance affects how quickly bacteria die when exposed to bactericidal antibiotics, finding that resistance can both speed up and slow down death rates depending on the type of resistance.

Contribution

The study reveals that resistance determinants can have epistatic interactions and influence bacterial death rates differently during early and persistent phases of antibiotic exposure.

Findings

Nalidixic acid or rifampicin-resistant single mutants decayed faster than sensitive cells during the early phase.

Double-resistant mutants showed prolonged survival, indicating epistatic interactions between resistance mutations.

Plasmid-carrying bacteria exhibited altered persistent-phase death rates compared to plasmid-free cells.

Abstract

Objectives: Antibiotic-resistant bacteria are widespread, with resistance arising from chromosomal mutations and resistance genes located in the chromosome or in mobile genetic elements. While resistance determinants often reduce bacterial growth rates, their influence on bacterial death under bactericidal antibiotics remains poorly understood. When bacteria are exposed to bactericidal antibiotics to which they are susceptible, they typically undergo a two-phase decline: a fast initial exponentially decaying phase, followed by a persistent slow-decaying phase. This study examined how resistance determinants affect death rates during both phases. Methods: We analyzed the death rates of ampicillin-exposed Escherichia coli populations of strains sensitive to ampicillin but resistant to nalidixic acid, rifampicin, or both, and bacteria carrying the conjugative plasmids RN3 or R702. Results: Single mutants resistant to nalidixic acid or rifampicin decayed faster than sensitive cells during the early phase, whereas the double-resistant mutant exhibited prolonged survival. These contrasting impacts suggest epistatic interactions between both chromosomal mutations. Persistent-phase death rates for chromosomal mutants did not differ significantly from wild-type cells. In contrast, plasmid-carrying bacteria displayed distinct dynamics: R702 plasmid-bearing cells showed higher persistent-phase death rates than plasmid-free cells, while RN3 plasmid-bearing cells exhibited lower rates. Conclusions: Bactericidal antibiotics may kill bacteria resistant to other antibiotics more effectively than wild-type cells. Moreover, epistasis may occur when different resistance determinants occur in the same cell, impacting the bactericidal potential of the antibiotic of choice. These results have significant implications for optimizing bacterial eradication protocols in clinical settings, as well as in animal health and industrial food safety management.

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