A one health genomic investigation of gentamicin resistance in Salmonella from human and chicken sources in Canada, 2014-2017

Objectives: We investigated whether the increased prevalence of gentamicin resistance in Salmonella from human infections was related to a similar increased prevalence in isolates from broiler chickens and whether this increase may have been due to co-selection from use of lincomycin-spectinomycin in chickens on farms. Methods: Whole genome sequencing was performed on gentamicin-resistant (gen-R) Salmonella isolates from human and chicken sources collected from 2014-2017 by the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). We determined the genomic relatedness of strains and characterized resistance genes and plasmids. Results: From 2014-2017, 247 isolates of gen-R Salmonella were identified by CIPARS: 188 were from humans and 59 from chicken sources (26 from live animals on farm and 33 from retail meat). The five most common gen-R serovars were Heidelberg (n=93, 31.5%), 4,[5],12:i:- (n=42, 14.2%), Kentucky (n=37, 12.5%), Infantis (n=33, 11.2%), and Typhimurium (n=23, 7.8%). Phylogenomic analysis revealed that for S. Heidelberg and S. Infantis, there were closely related isolates from human and chicken sources. In both sources, resistance to gentamicin and spectinomycin was most frequently conferred by aac(3)-VIa and ant(3’’)-Ia , respectively. Plasmid closure confirmed linkages of gentamicin and spectinomycin resistance genes and revealed instances of similar plasmids from both sources. Conclusions: Gentamicin and spectinomycin resistance genes were linked on the same plasmids, and some plasmids and isolates from humans and chickens were genetically similar, suggesting that the use of lincomycin-spectinomycin in chickens may be selecting for gentamicin-resistant Salmonella in broiler chickens and that these resistant strains may be acquired by humans.

Genotoxic Agents Produce Stressor-specific Spectra of Spectinomycin Resistance Mutations based on Mechanism of Action and Selection in Bacillus subtilis

Mutagenesis is integral for bacterial evolution and the development of antibiotic resistance. Environmental toxins and stressors are known to elevate the rate of mutagenesis through direct DNA toxicity known as stress-associated mutagenesis, or via a more general stress-induced process that relies on intrinsic bacterial pathways. Here, we characterize the spectra of mutations induced by an array of different stressors using high-throughput sequencing to profile thousands of spectinomycin resistant colonies of Bacillus subtilis . We found 69 unique mutations in the rpsE and rpsB genes, and that each stressor leads to a unique and specific spectrum of antibiotic resistance mutations. While some mutations clearly reflected the DNA-damage mechanism of the stress, others were likely the result of a more general stress-induced mechanism. To determine the relative fitness of these mutants under a range of antibiotic selective pressure, we used multi-strain competitive fitness experiments and found an additional landscape of fitness and resistance. The data presented here support the idea that the environment in which the selection is applied (mutagenic stressors that are present), and changes in local drug concentration, can significantly alter the path to spectinomycin resistance in B. subtilis .

Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018

We describe a gonorrhoea case with combined high-level azithromycin resistance and ceftriaxone resistance. In February 2018, a heterosexual male was diagnosed with gonorrhoea in the United Kingdom following sexual intercourse with a locally resident female in Thailand and failed treatment with ceftriaxone plus doxycycline and subsequently spectinomycin. Resistance arose from two mechanisms combining for the first time in a genetic background similar to a commonly circulating strain. Urgent action is essential to prevent further spread.

Characterization of Spectinomycin Resistance in Streptococcus suis Leads to Two Novel Insights into Drug Resistance Formation and Dissemination Mechanism

ABSTRACTSpectinomycin is an aminocyclitol antibiotic used clinically to treat a variety of infections in animals. Here, we characterized drug resistance prevalence in clinicalStreptococcus suisisolates and discovered a novel resistance mechanism in which the s5 mutation (Gly26Asp) results in high spectinomycin resistance. Additionally, a novel integrative and conjugative element encompassing a multidrug resistancespw_like-aadE-lnu(B)-lsa(E) cluster and a cadmium resistance operon were identified, suggesting a possible cause for the wide dissemination of spectinomycin resistance inS. suis.