Comparing gut resistome composition among patients with acute Campylobacter infections and healthy family members

Abstract

Campylobacter commonly causes foodborne infections and antibiotic resistance is an imminent concern. It is not clear, however, if the human gut ‘resistome’ is affected by Campylobacter during infection. Application of shotgun metagenomics on stools from 26 cases with Campylobacter infections and 44 healthy family members (controls) identified 406 unique antibiotic resistance genes (ARGs) representing 153 genes/operons, 40 mechanisms, and 18 classes. Cases had greater ARG richness (p < 0.0001) and Shannon diversity (p < 0.0001) than controls with distinct compositions (p = 0.000999; PERMANOVA). Cases were defined by multidrug resistance genes and were dominated by Proteobacteria (40.8%), specifically those representing Escherichia (20.9%). Tetracycline resistance genes were most abundant in controls, which were dominated by Bacteroidetes (45.3%) and Firmicutes (44.4%). Hierarchical clustering of cases identified three clusters with distinct resistomes. Case clusters 1 and 3 differed from controls containing more urban and hospitalized patients. Relative to family members of the same household, ARG composition among matched cases was mostly distinct, though some familial controls had similar profiles that could be explained by a shorter time since exposure to the case. Together, these data indicate that Campylobacter infection is associated with an altered resistome composition and increased ARG diversity, raising concerns about the role of infection in the spread of resistance determinants.

Recovery of the gut microbiome following enteric infection and persistence of antimicrobial resistance genes in specific microbial hosts

“…Among the key differences observed, cases had more multi-compound and multi-drug resistance genes during infection than post-recovery, whereas tetracycline, MLS, and aminoglycoside resistance genes were more abundant in the recovered (follow-up) sample. Diverse sets of ARGs have previously been found in otherwise healthy individuals as well [10, 41, 42], providing additional support for the human gut as an important reservoir of antibiotic resistance determinants [14].…”

“…The AmrPlusPlus v2.0 pipeline was used for quality control checking, aligning, and annotating metagenomic fragments with the MEGARes 2.0 database [16] and previously described parameters [10]. Reads were mapped to human genome GRCh38 (GRCh38_latest_genomic.fna.gz, downloaded December 2020) in RefSeq using the Burrows-Wheeler Aligner (BWA) [17] and removed using SAMTools [18] and BEDTools [19].…”

“…More recently, we have documented shifts in the gut resistome, or compilation of antimicrobial resistance genes (ARGs), among patients with Campylobacter infections when compared to their healthy family members [10]. The potential ecological repercussions relevant to recovery from enteric infection, however, have yet to be explored.…”

“…Moreover, 91 household members (controls) linked to 38 of the 60 patients submitted stools for comparison 5-29 weeks after the cases' infection. Resistome data from Campylobacter patients were examined previously [10], though no prior metagenome analyses were performed on the post-recovery samples.…”

“…Others have also demonstrated an increase in the proportion of Proteobacteria upon infection with Salmonella , Campylobacter , Shigella , and other pathogens in multiple host organisms [6–9]. More recently, we have documented shifts in the gut resistome, or compilation of antimicrobial resistance genes (ARGs), among patients with Campylobacter infections when compared to their healthy family members [10]. The potential ecological repercussions relevant to recovery from enteric infection, however, have yet to be explored.…”