Insights into Antibiotic Resistance Through Metagenomic Approaches

Robert Schmieder; Robert Edwards

Disclosures

Future Microbiol. 2012;7(1):73-89. 

In This Article

Abstract and Introduction

Abstract

The consequences of bacterial infections have been curtailed by the introduction of a wide range of antibiotics. However, infections continue to be a leading cause of mortality, in part due to the evolution and acquisition of antibiotic-resistance genes. Antibiotic misuse and overprescription have created a driving force influencing the selection of resistance. Despite the problem of antibiotic resistance in infectious bacteria, little is known about the diversity, distribution and origins of resistance genes, especially for the unculturable majority of environmental bacteria. Functional and sequence-based metagenomics have been used for the discovery of novel resistance determinants and the improved understanding of antibiotic-resistance mechanisms in clinical and natural environments. This review discusses recent findings and future challenges in the study of antibiotic resistance through metagenomic approaches.

Introduction

Infectious diseases are the second-leading cause of death globally and the most significant cause of death in children.[1,2] Antibiotics represent one of the largest therapeutic categories used in the treatment of infectious diseases caused by bacteria, but the successful use of any therapeutic agent is compromised by the potential development of tolerance or resistance to that compound from the time it is first employed. In clinical environments, pathogenic and commensal bacteria are challenged with high concentrations of antibiotics and bacteria have become resistant to most of the antibiotics developed.[3] Within the hospital setting, resistance pathogens often emerge within a few years after a new antibiotic is introduced (Figure 1). The spread of resistant bacteria and resistance genes depends on different factors but the major pressure is antibiotic usage.[4] Nosocomial (hospital-linked) infections result in approximately 100,000 deaths and cost more than US$25 billion per year in the USA alone. Worldwide, it is estimated that 5–10% of patients entering hospitals develop an infection as a result of their stay.[101] Despite the problem of antibiotic resistance in infectious bacteria, little is known regarding the diversity, distribution and origins of resistance genes, especially for the unculturable majority of environmental bacteria.

Figure 1.

Antibiotic resistance evolution showing the rapid development of resistance for several classes of antibiotics. The bars mark the time from the introduction of an antibiotic to the clinic until the first clinical case of resistance to that antibiotic was reported. The high number of available antibiotics during the 1950s and 1960s attributed to the longer times until the first resistance case was reported (e.g., for nalidixic acid). If the time frames for the same antibiotic differed between the data sources, the shorter time frame was used.
Data taken from [94–97].

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