I have heard of many large scale omics studies and their resultant “omes”, but it was only last week when I was reading a review in the Journal Cell on drug resistance in bacteria did I chance on a reference to the soil bacteria resistome , which was published by De Costa et. al. almost a year ago.
The paper deals with mapping the spectrum of antibiotic resistance among 480 streptomyces , the bacteria that produce several of the classes of antibiotics to kill other soil dwelling microbes. These microbes also encode a myriad of resistance mechanisms to make sure they survive the battle themselves. The resistance mechanisms brought into play by these soil dwelling bugs mimic those seen in clinically relevant bacteria. Given that its more a question of WHEN and not IF most of these mechanisms will surface in the clinical world.Therefore characterizing the diversity and density of resistance mechanisms prevalent in the environment is of extreme importance makes their study extremely relevant given the emergence of many super-bugs worldwide. The most surprising finding of the study was the diversity and density of resistance mechanisms present across all the strains.
The paper tested resistance to 20 different antibiotics belonging to every known class of antibiotics produced. Shockingly several of the bacteria were resistant to all 20 of them , with the average bacterium resistant to at least 7 different classes of antibiotics. Some of the antibiotics tested, were ineffective in almost 100% of the cases . Surprisingly the newly launched daptomycin which is effective against some multi-drug resistant microbes found in hospitals etc, was inactive in almost all of the soil isolates.
The authors also tested the resistome for possible mechanisms of inactivation and offered the possibility that possible novel mechanisms as well as variations of known mechanisms were operational and present in the resistome. The resistome illustrates how clever micobes are at outsmarting even the most well thought out antibiotic. Before we even think of creating an antibiotic to rule over all antibiotics , the chances that resistance to it is lurking in some niche in the microbe world seems to be quite likely. Although the resistome cannot predict how likely these resistance mechanisms are to transfer from the soil to a bug that can create problems when it sweeps through a hospitals ward: But it does make a case for using modern tools to address possible drug discovery in this class of drugs that indeed introduced chemotherapeutics to the everyday people.
Superbugs have been the stuff of many a popular cover story. Drug resistant tuberculosis , cholera , malaria etc continue to wreak havoc in the developing world. Recent articles in Nature and other journals spoke of the trials and tribulations of platensimycin , the only new class of antibiotic to be discovered in nearly two decades. Even that was hardly “resistance proof” in that over-expression of its target protein was able to confer resistance to the bug. Although the resistome, you could argue makes the case for the absence of a resistance proof antibiotic it definitely underscores the importance of improving the diversity of our arsenals against infectious bacteria. Given that our pace of discovery of antibiotics seems to be slower and slower, the resistome puts some quantitative muscle behind the cries for renewed drug discovery efforts in this area.