Transcriptional profiling of extraintestinal Escherichia coli exposed to cranberry pomace extracts alone or in combination with ceftriaxone

Abstract

Extraintestinal pathogenic Escherichia coli (ExPEC) includes several serotypes that have been associated with colibacillosis in poultry, as well as urinary tract infections and newborn meningitis in humans. This study investigated the antimicrobial activities of ceftriaxone (AXO) and cranberry pomace extracts (CRAN) alone or in combination (CC) against multidrug-resistant (MDR) ExPEC from broiler. The growth-inhibitory activity of CRAN and synergy tests by a checkerboard method were determined in cation-adjusted Mueller–Hinton broth (CAMHB). The transcriptomic profile of the MDR E. coli O7:H18 (ST38) grown in CAMHB supplemented with sub-inhibitory concertation of CRAN and AXO alone or in combination was obtained by RNA-seq. The MIC of CRAN for all isolates was 16 mg/mL. An additive activity was observed between 4 mg/mL of CRAN and 4 μg/mL of AXO. Compared to the control, the transcriptomic analysis revealed that 4 mg/ml of (1/4MIC) CRAN and its combination with 4 μg/mL of (1/8MIC) AXO (CC) exposures resulted in 727 and 712 differentially expressed genes, respectively (false discovery rate < 0.001 and log2-fold change > 2), in the studied E. coli. Major virulence genes including adhesins (fim, flg, csg, and yad), protectins (omp, tra, waa, and hly), secretion systems (hof, pho, and vir), and quorum sensing (lsr), which are energetically expensive for bacteria, were downregulated. Most importantly, 1/4MIC of CRAN or CC downregulated the β-lactamase blaCMY-2 and efflux pump including tolC, mdtEIJ, gadEW, and their regulator gene evgS, while upregulating the cysteine biosynthesis and oxidative stress-related regulatory genes including cys, dmlA, sbp, nrdGHI, soxSR, and rpoH. Downregulation of multiple enzymes involved in TCA cycles and upregulation of Fe–S cluster coordinated by Cys and Isc proteins reflect the regulation of energy metabolism of the studied E. coli upon CRAN or CC exposure. The downregulation of outer membrane protein genes that control permeability barriers, along with different antimicrobial resistance genes, demonstrates that CRAN may have the unique potential to enhance the antimicrobial activities of third-generation cephalosporins such as AXO against MDR E. coli.

Microbiome of Ceca from Broiler Chicken Vaccinated or Not against Coccidiosis and Fed Berry Pomaces

“…Despite the fact that most E. coli strains are harmless commensals, pathogenic strains such as avian pathogenic E. coli can cause severe respiratory and systemic infections (colibacillosis) in birds [ 32 , 33 ]. Cranberry pomace extracts have been reported to decrease motility and biofilm formation of pathogenic E. coli [ 34 , 35 ]. The berry pomace as a feed ingredient may provide undigested nutrients (fibers) for fermentation to produce compounds that may stimulate the growth of beneficial bacteria, including some Lactobacillus species found in the chicken gut because of their ability to de-conjugate bile acids and acid tolerance ability [ 28 ].…”

“…The lower prevalence of some VGs in birds fed berry pomaces may be due to the anti-virulence effects of some of their compounds, such as proanthocyanins [ 41 , 42 ]. Down-expression of genes involved in adhesion, motility, and biofilm formation, and upregulation of genes involved in iron metabolism and stress responses in Salmonella and E. coli from broiler have been reported [ 34 , 43 ].…”

Natural Antimicrobial Mixtures Disrupt Attachment and Survival of E. coli and C. jejuni to Non-Organic and Organic Surfaces

“…Resveratrol acts by regulating protein levels in two-component systems, chemotaxis proteins (including the fimC gene). Combating multidrug-resistant extraintestinal pathogenic Escherichia coli cetriaxone (AXO) and cranberry pomace extracts (CRAN) appears to be an effective procedure [63]. A combination of 4 mg/mL CRAN and 4 µg/mL AXO was considered to have minimal inhibitory concentrations, and exposure of bacteria to these concentrations resulted in downregulation of virulence genes.…”