Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC)

Autor: Gireesh Rajashekara, Issmat I. Kassem, Yosra A. Helmy, Dipak Kathayat, Loic Deblais
Rok vydání: 2018
Předmět:
0301 basic medicine
THP-1 Cells
Antibiotics
Moths
biofilm
Lactones
chemistry.chemical_compound
Pathogenic Escherichia coli
Escherichia coli Infections
autoinducer-2
biology
Vibrio harveyi
Quorum Sensing
macrophages
Infectious Diseases
motility
Research Paper
Microbiology (medical)
animal structures
Virulence Factors
medicine.drug_class
chicken
030106 microbiology
Immunology
Virulence
quorum sensing inhibitors
Microbiology
lcsh:Infectious and parasitic diseases
Small Molecule Libraries
03 medical and health sciences
Escherichia coli
Homoserine
medicine
Animals
Humans
lcsh:RC109-216
Poultry Diseases
Bacterial disease
APEC
wax moth model
Biofilm
biology.organism_classification
infection
Culture Media
Autoinducer-2
virulence
Quorum sensing
chemistry
Biofilms
gene expression
Parasitology
Caco-2 Cells
Chickens
Zdroj: Virulence, Vol 9, Iss 1, Pp 1640-1657 (2018)
Virulence
ISSN: 2150-5608
2150-5594
Popis: Colibacillosis caused by avian pathogenic E. coli (APEC), is an economically important bacterial disease of poultry. APEC are a subgroup of extra intestinal pathogenic E. coli (ExPEC) and poultry are considered potential sources of foodborne ExPEC to humans. Currently, APEC infections in poultry are controlled by antibiotics and/or vaccination; however, their effect is limited due to emergence of antibiotic resistant strains and infections with heterologous serotypes. Therefore, novel approaches are needed. Here, using the bioluminescent quorum sensing (QS) autoinducer 2 (AI-2) indicator Vibrio harveyi BB170, we screened the cell free culture supernatant of APEC O78 prepared from cultures grown in the presence of 4,182 small molecules (SMs; 100 μM). A total of 69 SMs inhibited > 75% of APEC O78 AI-2 activity in the indicator bacteria. Ten SMs that showed highest AI-2 inhibition were selected for further studies. Most of these SMs inhibited the AI-2 activity of other APEC serotypes and significantly reduced APEC O78 biofilm formation and motility. Most compounds showed minimal toxicity on human intestinal cells (Caco-2), chicken macrophage (HD-11), and chicken and sheep red blood cells, and reduced APEC survival in HD-11 and THP-1 macrophages. The SMs induced no or minimal toxicity and conferred protection against APEC in wax moth larval model. SMs affected the expression of APEC O78 QS, virulence, biofilm and motility associated genes providing insight on their potential mode(s) of action. Further testing in chickens will facilitate development of these SMs as novel therapeutics to control APEC in poultry and thereby also reduce zoonotic transmission.
Databáze: OpenAIRE
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