Population analysis of heavy metal and biocide resistance genes in Salmonella enterica from human clinical cases in New Hampshire, United States

Abstract

Microbes frequently encounter heavy metals and other toxic compounds generated from natural biogeochemical processes and anthropogenic activities. Here, we analyzed the prevalence and association of genes conferring resistance to heavy metals, biocides, and antimicrobial compounds in 394 genome sequences of clinical human-derived S. enterica from New Hampshire, USA. The most prevalent was the gold operon (gesABC-golTSB), which was present in 99.2% of the genomes. In contrast, the other five heavy metal operons (arsenic, copper, mercury, silver, tellurite) were present in 0.76% (3/394)–5.58% (22/394) of the total population. The heavy metal operons and three biocide resistance genes were differentially distributed across 15 sequence types (STs) and 16 serotypes. The number of heavy metal operons and biocide resistance genes per genome was significantly associated with high number of antimicrobial resistance (AMR) genes per genome. Notable is the mercury operon which exhibited significant association with genes conferring resistance to aminoglycosides, cephalosporins, diaminopyrimidine, sulfonamide, and fosfomycin. The mercury operon was co-located with the AMR genes aac(3)-IV, ant(3”)-IIa, aph(3’)-Ia, and aph(4)-Ia, CTX-M-65, dfrA14, sul1, and fosA3 genes within the same plasmid types. Lastly, we found evidence for negative selection of individual genes of each heavy metal operon and the biocide resistance genes (dN/dS < 1). Our study highlights the need for continued surveillance of S. enterica serotypes that carry those genes that confer resistance to heavy metals and biocides that are often associated with mobile AMR genes. The selective pressures imposed by heavy metals and biocides on S. enterica may contribute to the co-selection and spread of AMR in human infections.

The characterisation of antimicrobial resistantEscherichia colifrom dairy calves

“…The copyright holder for this preprint this version posted April 3, 2023. ; https://doi.org/10.1101/2023.04.03.533045 doi: bioRxiv preprint One E. coli strain in our study also harboured the mer operon on the same plasmid as the tetA, sul1, and ant(3")-Ia resistance genes. The co-location of tetracycline, sulphonamide and aminoglycoside encoding resistance genes with the mercury operon on IncF plasmids has been previously described (Gaeta et al, 2022;Souza et al, 2022;Zhao et al, 2020) and the presence of the mer operon was positively correlated with sulphonamide and aminoglycoside resistance genes, but not tetracycline resistance genes (Souza et al, 2022). Both heavy metals and disinfectants have previously been shown to co-select for resistance genes (Baker-Austin et al, 2006;Gaeta et al, 2020;Mazhar et al, 2021).…”

The characterisation of antimicrobial resistant Escherichia coli from dairy calves

“…coli strain in our study also harboured the mer operon on the same plasmid as the tetA , sul1 , and ant(3’)-Ia resistance genes. The co-location of tetracycline, sulphonamide and aminoglycoside encoding resistance genes with the mercury operon on IncF plasmids has been previously described [54, 64, 65] and the presence of the mer operon was positively correlated with sulphonamide and aminoglycoside resistance genes, but not tetracycline resistance genes [65].…”

Management factors influenceSalmonellapersistence in reused poultry litter over three successive flocks

“…Importantly, strains harboring ARGs which confer resistance to antimicrobials critically important to human medicine (World Health Organization, 2019), as well as those possessing VF increasing pathogenicity to humans, will pose a threat and will be harder to treat in the event contaminated food products reach consumers (Fricke et al ., 2009; Jajere, 2019; Zakaria et al ., 2022). Additionally, the use of heavy metals in chicken production, such as copper for growth promotion and/or sanitation of water lines, has led to the discovery that genes conferring metal resistance are often carried on the same mobile elements as ARGs and VFs (Dziewit et al ., 2015; Pal et al ., 2015; Bukowski et al ., 2019; Souza et al ., 2022). Resistance to metals may increase the virulence of a bacterial pathogen, e.g., overcoming iron toxicity and invading and colonizing different tissue types (Nairz et al ., 2015), as well as give a competitive advantage to strains in production environments where metals are used for antimicrobial agents (Bearson et al ., 2019).…”

“…Importantly, strains harboring ARGs which confer resistance to antimicrobials critically important to human medicine (World Health Organization, 2019), as well as those possessing VF increasing pathogenicity to humans, will pose a threat and will be harder to treat in the event contaminated food products reach consumers (Fricke et al, 2009;Jajere, 2019;Zakaria et al, 2022). Additionally, the use of heavy metals in chicken production, such as copper for growth promotion and/or sanitation of water lines, has led to the discovery that genes conferring metal resistance are often carried on the same mobile elements as ARGs and VFs (Dziewit et al, 2015;Pal et al, 2015;Bukowski et al, 2019;Souza et al, 2022).…”