Novel small molecules affecting cell membrane as potential therapeutics for avian pathogenic Escherichia coli

Dipak Kathayat,Yosra A Helmy,Gireesh Rajashekara,Loic Deblais

doi:10.1038/s41598-018-33587-5

Dipak Kathayat, Yosra A Helmy + Show 2 more

Open Access

https://doi.org/10.1038/s41598-018-33587-5

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Journal: Scientific Reports	Publication Date: Oct 17, 2018
Citations: 25	License type: open-access

Affiliation: The Ohio State University

Abstract

Avian pathogenic Escherichia coli (APEC), a most common bacterial pathogen of poultry, causes multiple extra-intestinal diseases in poultry which results in significant economic losses to the poultry industry worldwide. In addition, APEC are a subgroup of extra-intestinal pathogenic E. coli (ExPEC), and APEC contaminated poultry products are a potential source of foodborne ExPEC infections to humans and transfer of antimicrobial resistant genes. The emergence of multi-drug resistant APEC strains and the limited efficacy of vaccines necessitate novel APEC control approaches. Here, we screened a small molecule (SM) library and identified 11 SMs bactericidal to APEC. The identified SMs were effective against multiple APEC serotypes, biofilm embedded APEC, antimicrobials resistant APECs, and other pathogenic E. coli strains. Microscopy revealed that these SMs affect the APEC cell membrane. Exposure of SMs to APEC revealed no resistance. Most SMs showed low toxicity towards chicken and human cells and reduced the intracellular APEC load. Treatment with most SMs extended the wax moth larval survival and reduced the intra-larval APEC load. Our studies could facilitate the development of antimicrobial therapeutics for the effective management of APEC infections in poultry as well as other E. coli related foodborne zoonosis, including APEC related ExPEC infections in humans.

Highlights

Avian pathogenic E. coli (APEC), an extra-intestinal pathogenic E. coli (ExPEC), is one of the most common bacterial pathogens affecting chickens, turkeys, and other avian species[1,2]
Small molecule (SM) library was obtained from ChemBridge at 10 mM concentration dissolved in 100% dimethyl sulfoxide (DMSO) in 96 well plates and plates were stored at −80 °C until further use
One percent DMSO was used as control, which did not affect the growth of Avian pathogenic Escherichia coli (APEC), only DMSO concentration of 8% and above was inhibitory to APEC (Fig. S3)

Summary

Introduction

Avian pathogenic E. coli (APEC), an extra-intestinal pathogenic E. coli (ExPEC), is one of the most common bacterial pathogens affecting chickens, turkeys, and other avian species[1,2]. APEC causes multiple extra-intestinal infections in poultry such as airsacculitis, perihepatitis, pericarditis, peritonitis, omphalitis, salphingitis, and cellulitis which subsequently leads to high morbidity and mortality (up to 20%), reduced body weight gain and egg production, and increased carcass condemnation at slaughter (up to 45%), resulting in severe economic losses to the poultry industry worldwide[1]. Antimicrobial medication using tetracyclines, cephalosporins, sulfonamides, or quinolones is the major approach currently employed to reduce the incidence and mortality associated with APEC infections in poultry worldwide[4]. Multi-drug resistant (MDR) APEC strains resistant to tetracyclines, sulfonamides, aminoglycosides, β-lactam antimicrobials, quinolones, and colistin are reported worldwide including major poultry producing countries; United States, China, Brazil, and European Union[5,6,7,8]. Previous studies have identified SMs having antimicrobial activity against several human and animal pathogens[11,12,13]

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