The role of metagenomics in the fight against multidrug resistant pathogens

Introduction: We now live in a so called “post-antibiotic era”, what means that we can’t no longer rely on the great service antibiotics gave us during the past decades. Medicine and science are now at a point where antibiotic resistance building among bacteria is faster than the discovery of new antibiotics. It’s urgent to understand the antibiotic resistance genes and mechanisms and/or find new organisms which will produce new antibiotics. (Fouhy, et al., 2015)

Development of resistant bacteria – role of soil: Antibiotics originally derive from products produced by microorganisms – mostly soil bacteria (Fouhy, et al., 2015). It’s obvious that if they produce antibiotics to fight each other there will also resistances be built for defence. It's not yet clearly proven that resistance genes are given from soil bacteria to clinical bacteria or vice-versa. But an investigation made by Forsberg et al. (2012, found in de Castro et al., 2014) showed that a cultured non-pathogenic soil bacteria was able to confer seven resistance genes which had exactly the same nucleotide identity as resistance genes isolated from pathogens in clinics.
The soil environment is of such a huge interest because it’s the habitat of an enormous amount of microorganisms and as described above soil bacteria contain very similar resistance genes like human pathogens.

Former methods to study antibiotic resistances: Firstly the microorganisms had to come to the seen-world. That happened when the microscope was invented and life cycles of bacteria could be observed. The standard technique in microbiology laboratories was to cultivate the tiny organisms. At that time the challenge was to find the appropriate culture medium and to receive a pure culture. Only culturable organisms could be examined while the uncultured life wasn’t meant to exist. That changed in the mid-1980s, when scientists no longer could neglect the uncultured microorganisms and started to develop new techniques. (Handelsman, 2004)

Metagenomics – today’s most applied methods: Such a culture-independent analyse technique is metagenomics (de Castro et al., 2014). To understand antibiotic mechanisms and how resistance genes work is very important to predict and foresee novel antibiotic resistances. Metagenomics helps to detect active and inactive resistance genes whereof the latter also could confer resistance in certain circumstances. (Pehrsson et al., 2013 found in de Castro et al., 2014)
The big advantages of the culture-independence of metagenomics are the in situ investigations of bacterial resistance mechanisms (de Castro et al., 2014) and the access to environmental niches that have been inaccessible (Fouhy, 2015).
Fouhy et al. (2015) suggest to couple functional metagenomics with proteomics, because functional metagenomics on its own is not able to detect a resistance phenotype when several genes are coding for one resistance. Proteomics does not identify genes but proteins resulting from transcripts translation (Gupta et al., 2007 found in Fouhy et al., 2015). And proteins are the real warriors against antibiotics.

Risk of a novel resistance gene in a metagenome library: I would rather see it as a chance if a novel resistance gene occurs in a metagenome library, because this library is built up by researchers who are examining the vast unknown uncultured world. I assume that the novel resistance gene already existed and is now known and can be investigated. It’s no longer an unknown ‘enemy’. But if it’s really novel novel and didn’t exist before then it’s a concerning sign of further bacterial adaptation to antibiotics.

 

Literature:

de Castro, A. P., Fernandes, G., & Franco, O. L. (2014). Insights into novel antimicrobial compounds and antibiotic resistance genes from soil metagenomes. frontiers in Microbiology.

Fouhy, F., Stanton, C., Cotter , P. D., Hill, C., & Walsh, F. (2015). Proteomics as the final step in the functional metagenomics study of antimicrobial resistance. frontiers in Microbiology.

Handelsman, J. (2004). Metagenomics: Application of Genomics to Uncultured Microorganisms. American Society for Microbiology.