Proteomic analysis of the antimicrobial effects of sublethal concentrations of thymol on Salmonella enterica serovar Typhimurium.

Salmonella enterica serovar Typhimurium is an important foodborne pathogen that causes serious and extensive food contamination as well as disease and death worldwide. Considering the increasing severity of antibiotic resistance, antibiotic alternatives are urgently needed. As a natural biocide and a component of some essential oils from herbs, thymol is capable of killing various bacteria through a potentially unique mechanism, although the targets of thymol have not been completely elucidated. In this study, the variation in the whole proteome of Salmonella after thymol stress was evaluated using the SWATH multiplex technique. The strain Salmonella Typhimurium CVCC541 was treated with a sublethal concentration (75 µg/mL) of thymol, which rapidly increased the permeability of bacterial membranes at the tested concentration. Thymol destroyed the integrity of the bacterial membrane, as observed by transmission electron microscopy. The proteomes of the treated and untreated cells were characterized after an 8-h treatment. The proteomic analysis of thymol-treated cells indicated that 144 proteins exhibited upregulation or downregulation compared with the control cells, particularly those involved in cellular structure and metabolism. The results of this study showed that thymol may play an antimicrobial role in altering the membrane permeability, virulence change, and antioxidant response of Salmonella Typhimurium. The results of the present study provide an improved understanding of the proteomic response of Salmonella Typhimurium to thymol stress, including the identification of promising targets for the future exploration of innovative approaches to control Salmonella Typhimurium.

The role of MIF, cyclinD1 and ERK in the development of pulmonary hypertension in broilers.

Pulmonary hypertension (PH) is a major disease in the broiler breeding industry. During PH, the pulmonary artery undergoes remodelling, which is caused by pulmonary vascular smooth muscle cell proliferation. CyclinD1 regulates cell proliferation. This study investigated the role of cyclinD1 in the development of PH in broilers, and which bioactivators and signalling pathway are involved in the pathological process. The PH group contained 3-4-week-old broilers with clinical PH, and the healthy group broilers from the same flock without PH. Histopathology indicated pulmonary arterial walls were thicker in the PH group compared with the healthy group. Target gene expressions of macrophage migration inhibitory factor (MIF), extracellular signal-regulated kinase (ERK), and cyclinD1 detected by quantitative real-time PCR were upregulated in the PH group compared with the healthy group. Immunohistochemistry showed MIF, phosphorylated ERK (p-ERK) and cyclinD1 were present on pulmonary vascular walls; MIF was present in the cytoplasm of arterial endothelial cells and smooth muscle cells; p-ERK and cyclinD1 were present in smooth muscle cell cytoplasm. Western blotting demonstrated that MIF, p-ERKand cyclinD1 levels were significantly higher (P < 0.01) in the PH group compared with the healthy group. In summary, increased MIF in PH broiler pulmonary arteries upregulated cyclinD1 via the ERK signalling pathway to induce pulmonary vascular smooth muscle cell proliferation, causing pulmonary artery remodelling and hypertension.