Coping with antibiotic resistance: contributions from genomics

Gian Rossolini,Maria Thaller

doi:10.1186/gm136

Abstract

Antibiotic resistance is a public health issue of global dimensions with a significant impact on morbidity, mortality and healthcare-associated costs. The problem has recently been worsened by the steady increase in multiresistant strains and by the restriction of antibiotic discovery and development programs. Recent advances in the field of bacterial genomics will further current knowledge on antibiotic resistance and help to tackle the problem. Bacterial genomics and transcriptomics can inform our understanding of resistance mechanisms, and comparative genomic analysis can provide relevant information on the evolution of resistant strains and on resistance genes and cognate genetic elements. Moreover, bacterial genomics, including functional and structural genomics, is also proving to be instrumental in the identification of new targets, which is a crucial step in new antibiotic discovery programs.

Highlights

Antibiotic resistance is a public health issue of global dimensions with a signi cant impact on morbidity, mortality and healthcare-associated costs
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA, one of the most widespread and challenging resistant superbugs) were shown to be associated with an increased risk of mortality in comparison with infections of the same type caused by methicillin-susceptible S. aureus (MSSA)
Antibiotic resistance continues to evolve at a steady pace and the spreading of resistant strains has been facilitated by increasing international travel and migration, most pharmaceutical companies have recently chosen to restrict programs aimed at the discovery and development of new antibiotics. is has plunged the phenomenon of antibiotic resistance into a major crisis, with the increasing emergence of strains that are resistant to most or all antibiotics currently available for clinical use [3], which threatens to turn the clock back to the pre-antibiotic era

Summary

Introduction

Antibiotic resistance is a public health issue of global dimensions with a signi cant impact on morbidity, mortality and healthcare-associated costs. Modification by mutation, such as DNA topoisomerase or RNA polymerase modifications, conferring resistance to quinolones and rifampicin, respectively; third, drug target protection, for example ribosomal methylation conferring resistance to aminoglycosides or macrolides, or topoisomerase protection by Qnr proteins conferring resistance to quinolones; fourth, drug target bypass, for example peptidoglycan synthesis by a novel penicillinbinding-protein, PBP2a, conferring resistance to β‐lactams; fifth, impermeability, for example by loss of outer membrane porin channels, conferring resistance to carbapenems; and drug efflux, for example by Tet major facilitator superfamily (MFS)-type pumps, confer ring resistance to tetracyclines, or by tripartite resistancenodulation-cell division superfamily (RND)-type pumps, conferring a multidrug resistance phenotype.

Results

Conclusion