SignificanceBacterial infection has been extensively investigated; however, little is known about how bacterial pathogens timely shut down infecting machinery after successful infections. Here, a previously unknown sucrose–SghR/SghA–SAG–SA signaling axis was identified which controls the timing to shut off bacterial virulence expression and fine-tune host immune response. Sucrose, salicylic acid (SA), and its storage form SAG are small chemicals produced in plants whereas SghR is a bacterial sensor of sucrose and SghA is a bacterial enzyme that releases SA from SAG. Given that SA is an imperative signaling molecule in defense against a variety of microbial pathogens, these results depict a previously unknown 2-way chemical signaling cross-talk during microbe–host coevolution and shed mechanistic insights into host–bacteria interaction.

The cephalosporin antimicrobial drug cefquinome was administered to yellow cattle intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1 mg/kg of body weight in a two-period crossover study. The pharmacokinetic (PK) properties of cefquinome in serum, inflamed tissue-cage fluid (exudate), and noninflamed tissue-cage fluid (transudate) were studied using a tissue-cage model. The in vitro and ex vivo activities of cefquinome in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida (P. multocida) were determined. A concentration-independent antimicrobial activity of cefquinome was confirmed for levels lower than 4 × MIC. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the time that drug levels remain above the MIC (T > MIC) in serum was 14.10 h after intravenous and 14.46 h after intramuscular dosing, indicating a likely high level of effectiveness in clinical infections caused by P. multocida of MIC 0.04 μg/mL or less. These data may be used as a rational basis for setting dosing schedules, which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.

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The fluoroquinolone antimicrobial drug marbofloxacin was administered to yellow cattle intravenously and intramuscularly at a dose of 2 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of marbofloxacin in serum, inflamed tissue-cage fluid (exudate), and noninflamed tissue-cage fluid (transudate) were studied by using a tissue-cage model. The in vitro and ex vivo activities of marbofloxacin in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida (P. multocida) were determined. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 155.75, 153.00, and 138.88, respectively, after intravenous dosing and 160.50, 151.00, and 137.63, respectively, after intramuscular dosing. After intramuscular dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 21.13, 9.13, and 8.38, respectively. The ex vivo growth inhibition data after intramuscular dosing were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.25, 31.29, and 109.62, and slightly lower values were obtained for transudate and exudate. It is proposed that these findings might be used with MIC50 or MIC90 data to provide a rational approach to the design of dosage schedules which optimize efficacy in respect of bacteriological as well as clinical cures.

This study investigated the antipathogenic activity and probiotic potential of indigenous lactic acid bacteria (LAB) isolated from Chinese homemade pickles. In total, 27 samples were collected from different sites in China. Fifty-nine yielded pure colonies were identified by 16S rRNA gene sequencing as LAB and were initially evaluated for the antibacterial activity in vitro. Initial screening yielded Lactobacillus plantarum GS083, GS086, and GS090, which showed a broad-spectrum antibacterial activity against food-borne pathogens, especially multidrug-resistant pathogens. Meanwhile, organic acids were mainly responsible for the antimicrobial activity of the LAB strains, and the most abundant of these was lactic acid (19.32 ± 0.95 to 24.79 ± 0.40 g/l). Additionally, three L. plantarum strains demonstrated several basic probiotic characteristics including cell surface hydrophobicity, autoaggregation, and survival under gastrointestinal (GI) tract conditions. The safety of these isolates was also evaluated based on their antibiotic susceptibility, hemolytic risk, bile salt hydrolase activity, and existence of virulence or antibiotic resistance genes. All strains were safe at both the genomic and phenotypic levels. Therefore, L. plantarum GS083, GS086, and GS090 are fairly promising probiotic candidates and may be favorable for use as preservatives in the food industry.