Dataset Information

Mutational Evolution of Pseudomonas aeruginosa Resistance to Ribosome-Targeting Antibiotics.

ABSTRACT: The present work examines the evolutionary trajectories of replicate Pseudomonas aeruginosa cultures in presence of the ribosome-targeting antibiotics tobramycin and tigecycline. It is known that large number of mutations across different genes - and therefore a large number of potential pathways - may be involved in resistance to any single antibiotic. Thus, evolution toward resistance might, to a large degree, rely on stochasticity, which might preclude the use of predictive strategies for fighting antibiotic resistance. However, the present results show that P. aeruginosa populations evolving in parallel in the presence of antibiotics (either tobramycin or tigecycline) follow a set of trajectories that present common elements. In addition, the pattern of resistance mutations involved include common elements for these two ribosome-targeting antimicrobials. This indicates that mutational evolution toward resistance (and perhaps other properties) is to a certain degree deterministic and, consequently, predictable. These findings are of interest, not just for P. aeruginosa, but in understanding the general rules involved in the evolution of antibiotic resistance also. In addition, the results indicate that bacteria can evolve toward higher levels of resistance to antibiotics against which they are considered to be intrinsically resistant, as tigecycline in the case of P. aeruginosa and that this may confer cross-resistance to other antibiotics of therapeutic value. Our results are particularly relevant in the case of patients under empiric treatment with tigecycline, which frequently suffer P. aeruginosa superinfections.

SUBMITTER: Sanz-Garcia F

PROVIDER: S-EPMC6200844 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mutational Evolution of <i>Pseudomonas aeruginosa</i> Resistance to Ribosome-Targeting Antibiotics.

Sanz-García Fernando F Hernando-Amado Sara S Martínez José L JL

Frontiers in genetics 20181018

The present work examines the evolutionary trajectories of replicate <i>Pseudomonas aeruginosa</i> cultures in presence of the ribosome-targeting antibiotics tobramycin and tigecycline. It is known that large number of mutations across different genes - and therefore a large number of potential pathways - may be involved in resistance to any single antibiotic. Thus, evolution toward resistance might, to a large degree, rely on stochasticity, which might preclude the use of predictive strategies ...[more]

PMID: 30405685

Similar Datasets

Project description:Bacteria frequently encounter selection by both phages and antibiotics. However, our knowledge on the evolutionary interactions between phages and antibiotics are still limited. Here, we characterized a phage-resistant Pseudomonas aeruginosa variant PAO1-R1 that shows increased sensitivity to gentamicin and polymyxin B. Using whole genome sequencing, significant genome differences were observed between the reference P. aeruginosa PAO1 and PAO1-R1. Compared to PAO1, 64 gene-encoding proteins with nonsynonymous single nucleotide polymorphisms (SNPs) and 31 genes with insertion/deletion (indel) mutations were found in PAO1-R1. We observed a significant reduction in phage adsorption rate for both phage vB_Pae_QDWS and vB_Pae_W3 against PAO1-R1 and proposed that disruption of phage adsorption is likely the main cause for evolving resistance. Because the majority of spontaneous mutations are closely related to membrane components, alterations in the cell envelope may explain the antibiotic-sensitive phenotype of PAO1-R1. Collectively, we demonstrate that the evolution of phage resistance comes with fitness defects resulting in antibiotic sensitization. Our finding provides new insights into the evolutionary interactions between resistance to the phage and sensitivity to antibiotics, which may have implications for the future clinical use of steering in phage therapies. IMPORTANCE Bacteria frequently encounter the selection pressure from both antibiotics and lytic phages. Little is known about the evolutionary interactions between antibiotics and phages. Our study provides new insights into the trade-off mechanism between resistance to the phage and sensitivity to antibiotics. This evolutionary trade-off is not dependent on the outer membrane proteins (OMPs) of the multidrug efflux pumps. The disruption of phage adsorption that induced phage resistance and the changes in structure or composition of membranes are presumably one of the major causes for antibiotic sensitivity. Our finding may fill some gaps in the field of phage-host interplay and have implications for the future clinical use of steering in phage therapies.

Dataset Information

Mutational Evolution of Pseudomonas aeruginosa Resistance to Ribosome-Targeting Antibiotics.

Publications

Mutational Evolution of <i>Pseudomonas aeruginosa</i> Resistance to Ribosome-Targeting Antibiotics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets