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

Abstract

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. ARTICLE HISTORY

Prevalence, Antimicrobial Resistance Profiles, Virulence and Enterotoxins-Determinant Genes of MRSA Isolated from Subclinical Bovine Mastitis in Egypt

“…Subclinical mastitis is a significantly important disease, causing economic losses in the livestock industry, not only in Egypt, but also worldwide. Antibiotic resistance has increased among various bacterial pathogens, which is considered an emerging problem with a major public health concern due to the risk of resistance transmission to human as well as its influence on the effectiveness of the current antibiotic therapy [26][27][28][29]. Further, MRSA strains can cause nosocomial infections and high mortality in humans [3].…”

Arachidonic acid metabolism is elevated inMycoplasma gallisepticumandEscherichia colico-infection and induces LTC4 in serum as the biomarker for detecting poultry respiratory disease

“…MG is often associated with co-infection outbreaks of other pathogens, which may due to a down-regulation of the host immune response by MG infection [ 8 ]. Colibacillosis infection caused by avian pathogenic E.coli (APEC) is also an economically important bacterial disease in poultry [ 9 ]. Respiratory diseases may be induced by various viral and bacterial agents, either alone or in combination [ 10 ].…”

<p>Small Molecule Adjuvants Potentiate Colistin Activity and Attenuate Resistance Development in <em>Escherichia coli</em> by Affecting <em>pmr</em>AB System</p>

“…To corroborate the findings of mutation analysis, relative expression of pmrCAB and pmrH in APEC isolates (DMSO-1, DMSO-3, Col-1, Col-3, Col-5, Col-6, Col + SM2-2, Col + SM2-4, Col + SM2-6, Col + SM3-2, Col + SM3-5, and Col + SM3-6) was quantitated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) as described previously. 45,46 APEC isolates frozen in glycerol at −80°C were grown overnight at 37°C with shaking at 200 rpm and total RNA was extracted using RNeasy mini kit (Qiagen) following the manufacturer's instructions. RNA quantity and quality were measured using nanodrop 2000c spectrophotometer and 1% agarose gel electrophoresis.…”