Evolution of antibiotic cross‐resistance and collateral sensitivity in Staphylococcus epidermidis using the mutant prevention concentration and the mutant selection window

Abstract

In bacteria, evolution of resistance to one antibiotic is frequently associated with increased resistance (cross‐resistance) or increased susceptibility (collateral sensitivity) to other antibiotics. Cross‐resistance and collateral sensitivity are typically evaluated at the minimum inhibitory concentration (MIC). However, these susceptibility changes are not well characterized with respect to the mutant prevention concentration (MPC), the antibiotic concentration that prevents a single‐step mutation from occurring. We measured the MIC and the MPC for Staphylococcus epidermidis and 14 single‐drug resistant strains against seven antibiotics. We found that the MIC and the MPC were positively correlated but that this correlation weakened if cross‐resistance did not evolve. If any type of resistance did evolve, the range of concentrations between the MIC and the MPC tended to shift right and widen. Similar patterns of cross‐resistance and collateral sensitivity were observed at the MIC and MPC levels, though more symmetry was observed at the MIC level. Whole‐genome sequencing revealed mutations in both known‐target and nontarget genes. Moving forward, examining both the MIC and the MPC may lead to better predictions of evolutionary trajectories in antibiotic‐resistant bacteria.

Antifungal Activity of a Medical-Grade Honey Formulation against Candida auris

“…Resistance to fluconazole alone or combined with echinocandin and/or amphotericin B resistance did not affect the susceptibility of C. auris isolates to the medical-grade honey formulation, although the multiresistant isolates tended to be more sensitive. The increased susceptibility of multiresistant microorganisms to alternative treatments has been observed previously, and is known as collateral susceptibility [ 27 , 28 , 29 ]. Studies including larger numbers of multiresistant isolates should determine whether multiresistant C. auris also demonstrates collateral susceptibility.…”

Acquisition of Tigecycline Resistance by Carbapenem-Resistant Klebsiella pneumoniae Confers Collateral Hypersensitivity to Aminoglycosides

“…Development of collateral sensitivity is a widespread evolutionary trade-off that occurs in many Gram-negative and Gram-positive bacteria (Barbosa et al, 2017;Lozano-Huntelman et al, 2020). Only a limited number of studies have examined collateral sensitivity in Klebsiella pneumoniae.…”

Systematic Investigation of Resistance Evolution to Common Antibiotics Reveals Conserved Collateral Responses across Common Human Pathogens

“…To date, most of this work has been performed using specific laboratory-adapted strains ( 8 – 12 , 15 , 17 , 18 , 20 ) or a limited number of clinical isolates ( 6 , 13 , 14 , 16 ). While these studies have been vital to our understanding of CS in a wide variety of species, little remains known regarding the extent of evolutionary conservation or the universality of CS and CR across species ( 21 ).…”

“…CS is when resistance to one antibiotic simultaneously results in susceptibility to another (7). Over the last decade, several studies have considered how resistance evolution toward a single antibiotic effects CS and its converse, crossresistance (CR), for a wide variety of antibiotics and bacterial species (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The results of these works have been used to identify networks of drugs which can be used to drive resistance in a particular direction to take advantage of CS.…”