Efficacy of neomycin dosing regimens for treating enterotoxigenic Escherichia coli-related post-weaning diarrhoea in a Danish nursery pig herd not using medicinal zinc oxide

Morsing, Malene Kjelin; Larsen, Inge; Pedersen, Ken Steen; Weber, Nicolai Rosager; Nielsen, Jens Peter

doi:10.1186/s40813-022-00283-w

Cited by 4 publications

(1 citation statement)

References 16 publications

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“…Gentamicin (GEN) is applied in human medicine to treat a variety of bacterial infections including septicemia, meningitis and urinary tract infections 8 . Neomycin (NEO) is among the first drug choices in the pig industry to treat E. coli -related post-weaning diarrhea 9 , 10 .…”

Section: Introductionmentioning

confidence: 99%

Genome-wide identification of fitness-genes in aminoglycoside-resistant Escherichia coli during antibiotic stress

Wellner,

Alobaidallah,

Fei

et al. 2024

Sci Rep

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Resistance against aminoglycosides is widespread in bacteria. This study aimed to identify genes that are important for growth of E. coli during aminoglycoside exposure, since such genes may be targeted to re-sensitize resistant E. coli to treatment. We constructed three transposon mutant libraries each containing > 230.000 mutants in E. coli MG1655 strains harboring streptomycin (aph(3″)-Ib/aph(6)-Id), gentamicin (aac(3)-IV), or neomycin (aph(3″)-Ia) resistance gene(s). Transposon Directed Insertion-site Sequencing (TraDIS), a combination of transposon mutagenesis and high-throughput sequencing, identified 56 genes which were deemed important for growth during streptomycin, 39 during gentamicin and 32 during neomycin exposure. Most of these fitness-genes were membrane-located (n = 55) and involved in either cell division, ATP-synthesis or stress response in the streptomycin and gentamicin exposed libraries, and enterobacterial common antigen biosynthesis or magnesium sensing/transport in the neomycin exposed library. For validation, eight selected fitness-genes/gene-clusters were deleted (minCDE, hflCK, clsA and cpxR associated with streptomycin and gentamicin resistance, and phoPQ, wecA, lpp and pal associated with neomycin resistance), and all mutants were shown to be growth attenuated upon exposure to the corresponding antibiotics. In summary, we identified genes that are advantageous in aminoglycoside-resistant E. coli during antibiotic stress. In addition, we increased the understanding of how aminoglycoside-resistant E. coli respond to antibiotic exposure.

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Section: Introductionmentioning

confidence: 99%

Genome-wide identification of fitness-genes in aminoglycoside-resistant Escherichia coli during antibiotic stress

Wellner,

Alobaidallah,

Fei

et al. 2024

Sci Rep

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Genetic background of neomycin resistance in clinical Escherichia coli isolated from Danish pig farms

Subramani,

Menichincheri,

Pirolo

et al. 2023

Appl Environ Microbiol

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Neomycin is the first-choice antibiotic for the treatment of porcine enteritis caused by enterotoxigenic Escherichia coli . Resistance to this aminoglycoside is on the rise after the increased use of neomycin due to the ban on zinc oxide. We identified the neomycin resistance determinants and plasmid contents in a historical collection of 128 neomycin-resistant clinical E. coli isolates from Danish pig farms. All isolates were characterized by whole-genome sequencing and antimicrobial susceptibility testing, followed by conjugation experiments and long-read sequencing of eight selected representative strains. We detected 35 sequence types (STs) with ST100 being the most prevalent lineage (38.3%). Neomycin resistance was associated with two resistance genes, namely aph(3 ′ )-Ia and aph(3′)-Ib , which were identified in 93% and 7% of the isolates, respectively. The aph(3′)-Ia was found on different large conjugative plasmids belonging to IncI1α, which was present in 67.2% of the strains, on IncHI1, IncHI2, and IncN, as well as on a multicopy ColRNAI plasmid. All these plasmids except ColRNAI carried genes encoding resistance to other antimicrobials or heavy metals, highlighting the risk of co-selection. The aph(3′)-Ib gene occurred on a 19 kb chimeric, mobilizable plasmid that contained elements tracing back its origin to distantly related genera. While aph(3′)-Ia was flanked by either Tn 903 or Tn 4352 derivatives, no clear association was observed between aph(3′)-Ib and mobile genetic elements. In conclusion, the spread of neomycin resistance in porcine clinical E. coli is driven by two resistance determinants located on distinct plasmid scaffolds circulating within a highly diverse population dominated by ST100. IMPORTANCE Neomycin is the first-choice antibiotic for the management of Escherichia coli enteritis in pigs. This work shows that aph(3 ′ )-Ia and to a lesser extent aph(3′)-Ib are responsible for the spread of neomycin resistance that has been recently observed among pig clinical isolates and elucidates the mechanisms of dissemination of these two resistance determinants. The aph(3′)-Ia gene is located on different conjugative plasmid scaffolds and is associated with two distinct transposable elements (Tn 903 and Tn 4352 ) that contributed to its spread. The diffusion of aph(3′)-Ib is mediated by a small non-conjugative, mobilizable chimeric plasmid that likely derived from distantly related members of the Pseudomonadota phylum and was not associated with any detectable mobile genetic element. Although the spread of neomycin resistance is largely attributable to horizontal transfer, both resistance determinants have been acquired by a predominant lineage (ST100) associated with enterotoxigenic E. coli , which accounted for approximately one-third of the strains.

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Recombinant Saccharomyces cerevisiae EBY100/pYD1-FaeG: a candidate for an oral subunit vaccine against F4+ ETEC infection

Hu,

Li,

Duan

et al. 2024

Appl Environ Microbiol

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Diarrheal diseases attributable to multidrug-resistant F4+ enterotoxigenic Escherichia coli (ETEC) are escalating in severity, posing significant risks to the health and safety of both humans and animals. This study used Saccharomyces cerevisiae EBY100 to display the FaeG subunit of F4 colonizing factor as an oral vaccine against F4+ ETEC infection. Mice were orally immunized twice with 10 8 CFU of EBY100/pYD1-FaeG, followed by a challenge with F4+ ETEC EC6 on day 7 post-immunization. The results showed that the recombinant strain EBY100/pYD1-FaeG orally enhanced the growth of the small intestine villi, significantly boosted the expression of tight junction proteins ( ZO-1 , Occludin , MUC2 , and Claudin ) ( P < 0.05), and modulated the gut microbiota composition. Additionally, immunization with EBY100/pYD1-FaeG also upregulated the levels of IL-2, IL-4, and IFN-γ in the intestines of mice ( P < 0.01), while serum IgG and fecal sIgA titer significantly increased ( P < 0.05). These immune responses enhanced the capacity to fight against ETEC, leading to an increased survival rate of mice and relieved damage to tissues and organs of mice infection. In summary, the study suggested that the recombinant Saccharomyces cerevisiae EBY100/pYD1-FaeG could effectively stimulate the immune response and generate specific antibodies against F4+ ETEC, showing its potential to serve as a subunit oral vaccine candidate for preventing F4+ ETEC infection. IMPORTANCE The multidrug-resistant F4+ enterotoxigenic Escherichia coli (ETEC) strains are the primary clinical pathogens responsible for post-weaning diarrhea in piglets, resulting in substantial economic losses in the pig farming industry. In the study, we developed an oral vaccine candidate, Saccharomyces cerevisiae EBY100/pYD1-FaeG, to prevent diarrhea caused by multidrug-resistant F4+ ETEC. Oral administration of EBY100/pYD1-FaeG significantly enhanced immune responses, improved intestinal health, and provided protection against F4+ ETEC infection in mice. This approach offers a potential application prospect for preventing F4+ ETEC infections that lead to post-weaning diarrhea in clinical settings and provides a promising solution for addressing the growing threat of antibiotic resistance in bacterial pathogens.

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Efficacy of neomycin dosing regimens for treating enterotoxigenic Escherichia coli-related post-weaning diarrhoea in a Danish nursery pig herd not using medicinal zinc oxide

Cited by 4 publications

References 16 publications

Genome-wide identification of fitness-genes in aminoglycoside-resistant Escherichia coli during antibiotic stress

Genome-wide identification of fitness-genes in aminoglycoside-resistant Escherichia coli during antibiotic stress

Genetic background of neomycin resistance in clinical Escherichia coli isolated from Danish pig farms

Recombinant Saccharomyces cerevisiae EBY100/pYD1-FaeG: a candidate for an oral subunit vaccine against F4+ ETEC infection

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