Insights into Antibiotic Resistance Through Metagenomic Approaches

Robert Schmieder; Robert Edwards

Disclosures

Future Microbiol. 2012;7(1):73-89. 

In This Article

Antibiotic Resistance in Soil Microbial Communities

There are as many microorganisms in 1g of soil as there are humans on the entire planet,[53] and much less than 1% of those microbes are readily culturable by current methods.[54,55] Soil is most likely the ecosystem where antibiotic synthesis originally evolved[56] and soils from diverse locations around the world such as forest, prairie, agriculture and urban have been explored to develop new clinical and medicinal applications. As a result, over 80% of antibiotics in clinical use today originated from soil bacteria, either directly as natural products or as their semi-synthetic derivatives.[57]

The high density of antibiotic-producing bacteria makes soil a likely source of diverse antibiotic resistance determinants.[20,23,58,59] Molecular resistance mechanisms between clinical pathogens and the common soil bacterium Streptomyces were first shown to be similar in 1973.[60] Since then, numerous parallels have been identified between soil microorganisms and clinically important strains, and the abundance of pathogens that can survive in soil results in a potent mixture that can give rise to the emergence of antibiotic resistance in the clinical setting. In recent years, metagenomic approaches have been implemented to characterize the diversity and prevalence of resistance in soil bacteria.[61]

The metagenomic studies of soil environments show evidence that multiple diverse mechanisms for resistance are associated with microbes from different soil samples (Table 1). These studies also suggested that soil microbes are resistant to most antibiotics, and the broad activity of these resistance genes might afford protection against newly developed antibiotics.

It is assumed that many soil bacteria are naturally resistant to antibiotics such as β-lactams.[22,62] Allen et al. identified genes that mediate resistance to β-lactam antibiotics from remote Alaskan soil with no known exposure to anthropogenically derived antibiotics.[22] They performed functional metagenomics to allow comparison of antibiotic resistance between the Alaskan soil and soils subjected to human activity, and to search for florfenicol resistance genes.[59] Torres-Cortés et al. applied functional metagenomics to soil samples and identified a gene belonging to a new type of reductase conferring resistance to trimethoprim, a synthetic antibiotic that interferes with the production of tetrahydrofolic acid.[63]

Antibiotic resistance is common in soil bacteria. Nine clones expressing antibiotic resistance in E. coli to five different aminoglycoside antibiotics and one clone expressing tetracycline resistance were identified in a metagenomic library from soil samples.[20] These resistance proteins were less than 60% identical to previously published sequences, suggesting that soil microorganisms harbor more genetic diversity than previously assumed.[63] More recently, 446,000 clones comprising a soil-derived metagenomic library were screened for genes conferring resistance to tetracycline, β-lactams, or aminoglycoside antibiotics, which resulted in the identification of 13 different antibiotic-resistant clones.[23] The low level of sequence similarity from these clones suggests that these proteins may play a different role in natural environments. For example, it was proposed that antibiotics could, in reality, be signal molecules that help shape the structure of microbial communities.[64–66] Alternatively, resistance may be associated with adaption to, and survival in, nutrient-poor environments, and some bacteria can use antibiotics as a food source, presumably via resistance mechanisms they have developed.[67] Further studies on a more diverse subset of strains, especially slow-growing strains and those difficult to culture will be important to clarify the role of resistance in bacteria.

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