Revisiting Polymorphic Diversity of Aminoglycoside N-Acetyltransferase AAC(6′)-Ib Based on Bacterial Genomes of Human, Animal, and Environmental Origins

Abstract

The prevalence of aac(6′)-Ib variants has been demonstrated in numerous epidemiological studies. We revisited the polymorphic diversity of aminoglycoside 6’-N-acetyltransferase gene [aac(6′)-Ib] in the bacterial genome databases based on One Health perspectives. aac(6′)-Ib was searched against bacterial complete and draft genome databases of NCBI. Based on the major polymorphic residues 102, 117, and 179, taxonomy, ecology, and temporal emergence of bacterial isolates harboring variants of aac(6′)-Ib gene were evaluated using whole-genome sequences available in the databases. A total of 3,964 aac(6′)-Ib sequences were found to be present in the genomes of 34 bacterial genera, mostly found in Gammaproteobacteria. Among these, aac(6′)-Ib-cr variant, known to confer fluoroquinolone resistance, were increasingly detected in bacterial genomes and most abundant in the genera Klebsiella and Escherichia, thereby suggesting that these genera were the major reservoirs of the plasmid-mediated quinolone resistance (PMQR) determinant. The proportions of the cr variant were higher in animal and environmental isolates than in human isolates, among which the variant was dominant (>50%) in the genomes of intestinal, rectal, and fecal origins. In addition, our study suggested that the prevalence of the cr variant was associated with the occurrence of a variant with the mutation L117 (IbL). An integrated surveillance system for antimicrobial resistance in human, animal, and environmental sectors, based on whole-genome sequencing, would provide a better insight into the evolution, ecology, and epidemiology of antimicrobial-resistant bacteria.

Transferable Mechanisms of Quinolone Resistance from 1998 Onward

“…environments, probably being the most common and frequent TMQR. In addition to its presence in microorganisms from human samples, a recent report has shown a high prevalence of AAC(6=)Ib-cr in animal and environmental samples (400).…”

State of Knowledge on the Acquisition, Diversity, Interspecies Attribution and Spread of Antimicrobial Resistance between Humans, Animals and the Environment: A Systematic Review

“…However, the environment might be an important component of this system, especially considering it as an interface between humans and animals. This further enforces the need for expanding the One Health to a HSES concept, allowing a better investigation of all influencing factors and their complex interplay; this should be supported by various studies [27,31,33,34,52,55,59,75,76].…”

“…However, this data must also be integrated into a systematic approach by further elaborating upon epidemiological analysis, such as with the concept of HSES. The investigation of genetic changes, using metagenomic sequencing [33,49] and whole genome sequencing [34], could be an approach to better consider all the factors involved in AMR transmission. Stringent One Health/HSES epidemiological study designs, using cohort or case-control designs, minimize the potential sources of bias; therefore, they are necessary for elucidating the principal routes and dynamics of the spread of antibiotic resistant bacteria and antibiotic resistance genes between human, animal and environmental compartments.…”

“…However, many studies do not provide an integrated analysis of ARG prevalence and the phylogenetic situation to assess the similarity of different isolates within the same or different compartments [30]. There is evidence for a certain host or compartment specificity regarding the occurrence of ARGs/AMR bacteria [29,[31][32][33][34]. This could be compatible with the concept of the very limited AMR spread between different compartments, for example, only in the context of very close contact, such as people living in close proximity to animals (e.g., farming communities), or occupationally exposed people, such as farmers or veterinarians exposed to pigs [35].…”

“…Accordingly, it is crucial to clearly state the time and location of the sample acquisition, and/or limit research to a specific geographical location, in order to reduce the spatio-temporal bias and decrease the undesired exogenous variability. Several studies described a highly variable prevalence of antibiotic resistance over time, with either increasing or decreasing trends [34,[52][53][54]. Accordingly, the comparison of samples acquired at different time points can be very difficult.…”