Is antibiotic resistance in gut bacteria a threat to human health?

A study published in Nature Microbiology characterized potential determinants of antibiotic resistance in bacteria from the human intestine.

According to the World Health Organization, antibiotic-resistant bacteria are one of the largest health threats for the coming decades. Antibiotics are used to kill or slow growth of bacteria, but some bacteria are resistant to certain antibiotics. The overuse of antibiotics causes these resistant bacteria to out-compete other bacteria and form resistant strains. Infections caused by these antibiotic-resistant strains are extremely difficult to treat.

Some bacteria have a natural resistance to certain antibiotics. However, antibiotic resistance can also be acquired. Acquired resistance can arise from a mutation in a single bacterial cell or by transfer of antibiotic resistance genes from one strain to another. Genes are transferred through mobile genetic elements, which are segments of DNA that can be copied or taken from one bacterial cell and inserted into another.

Thousands of species of bacteria live in the human intestine. The vast majority of these species are harmless and do not cause disease. However, resistance also occurs in these gut bacteria, and some experts are concerned that antibiotic-resistance genes from these harmless bacteria could be transferred to disease-causing bacteria by mobile genetic elements.

Identification of antibiotic resistance genes in gut bacteria

Previous attempts to identify antibiotic resistance determinants in gut bacteria were unsuccessful. Ina study led by the Institut National de la Recherche Agronomique (INRA) in France and published in Nature Microbiology, researchers characterized proteins conferring resistance in human gut bacteria.

In this study, researchers developed a new tool to predict whether gut bacterial proteins are determinants of resistance. They called this tool pairwise comparative modeling (PCM). This tool compared their three-dimensional structures to known determinants of antibiotic resistance from other bacteria. PCM dramatically improved researchers’ ability to identify determinants of antibiotic resistance compared to other tools previously used.

Researchers used PCM to examine nearly 3.9 million proteins from fecal samples of 396 human participants in the MetaHIT project. With PCM, they predicted over 6000 of these proteins to be determinants of antibiotic resistance that are distantlyrelated to those of other species.

Antibiotic resistance determinants in gut bacteria are rarely transferred

The researchers found that few (7.9%) genes for these determinants of antibiotic resistance were located on mobile genetic elements. This suggests that there is low if any transfer of antibiotic resistance genes from gut bacteria to other bacteria.

Antibiotic resistancein disease-causing bacteria is a major threat to human health. However, thisstudy suggests that antibiotic resistant genes in harmless gut bacteria are nota major source of antibiotic resistance in disease-causing bacteria.

One limitation of this study is that PCM only detected proteins from highly abundant bacteria. Determinants of antibiotic resistance could be transferred to disease-causing bacteria from less abundant bacteria that were not represented in this study.

Researchers also identified potential determinants based on structural similarity to known determinants; however, there may be additional classes of determinants that were not detected in this study because they are not similar to known determinants of antibiotic resistance.

Written by Melissa H. Wong, MSc

Reference: Ruppé E,Ghozlane A, Tap J, et al. Prediction of the intestinal resistome by a three-dimensional structure-based method. 2018. Nat. Microbiol.DOI: 10.1038/s41564-018-0292-6