The oral microbiota is a reservoir for antimicrobial resistance: resistome and phenotypic resistance characteristics of oral biofilm in health, caries, and periodontitis

Abstract

Background Antimicrobial resistance (AMR) is an ever-growing threat to modern medicine and, according to the latest reports, it causes nearly twice as many deaths globally as AIDS or malaria. Elucidating reservoirs and dissemination routes of antimicrobial resistance genes (ARGs) are essential in fighting AMR. Human commensals represent an important reservoir, which is underexplored for the oral microbiota. Here, we set out to investigate the resistome and phenotypic resistance of oral biofilm microbiota from 179 orally healthy (H), caries active (C), and periodontally diseased (P) individuals (TRN: DRKS00013119, Registration date: 22.10.2022). The samples were analysed using shotgun metagenomic sequencing combined, for the first time, with culture technique. A selection of 997 isolates was tested for resistance to relevant antibiotics. Results The shotgun metagenomics sequencing resulted in 2,069,295,923 reads classified into 4856 species-level OTUs. PERMANOVA analysis of beta-diversity revealed significant differences between the groups regarding their microbiota composition and their ARG profile. The samples were clustered into three ecotypes based on their microbial composition. The bacterial composition of H and C samples greatly overlapped and was based on ecotypes 1 and 2 whereas ecotype 3 was only detected in periodontitis. We found 64 ARGs conveying resistance to 36 antibiotics, particularly to tetracycline, macrolide-lincosamide-streptogramin, and beta-lactam antibiotics, and a correspondingly high prevalence of phenotypic resistance. Based on the microbiota composition, these ARGs cluster in different resistotypes, and a higher prevalence is found in healthy and caries active than in periodontally diseased individuals. There was a significant association between the resistotypes and the ecotypes. Although numerous associations were found between specific antibiotic resistance and bacterial taxa, only a few taxa showed matching associations with both genotypic and phenotypic analyses. Conclusions Our findings show the importance of the oral microbiota from different niches within the oral cavity as a reservoir for antibiotic resistance. Additionally, the present study showed the need for using more than one method to reveal antibiotic resistance within the total oral biofilm, as a clear mismatch between the shotgun metagenomics method and the phenotypic resistance characterization was shown.

Upper respiratory microbial communities of healthy populations are shaped by niche and age

“…Unbiased examination of ARG carriage within nasal and oral microbiomes revealed unique patterns across each age groups, concordant with observed differences in community 13 compositions. The oral microbiome has recently become recognized as a resilient reservoir of ARGs, while the resistome of the nasal microbiome remains poorly understood [45][46][47]. Broadly, we find that body site appeared to have greater influence on ARG abundance, rather than age, with higher median ARG abundance in oral compared to nasal metagenomes.…”

Polymicrobial Bacterial Meningitis in a Patient with Chronic Suppurative Otitis Media: Case Report and Literature Review

“…There are only several published case reports [ 51 ]. Unfortunately, oral microbiota is an important underexplored reservoir for other infections and also for antimicrobial resistance [ 52 ].…”

Leveraging genomic signatures of oral microbiome-associated antibiotic resistance genes for diagnosing pancreatic cancer

“…ARGs play a crucial role in microbial populations and have gained significant attention in recent years due to their impact on human health [ 11 , 13 ], including their association with various diseases and their potential as diagnostic markers [ 14 ]. The presence of ARGs within the oral microbiome can provide insights into the microbial ecology, as well as antibiotic usage and exposure history of an individual [ 15 , 16 ].…”