The quorum-sensing (QS) system is an intercellular cell-cell communication mechanism that controls the expression of genes involved in a variety of cellular processes and that plays critical roles in the adaption and survival of bacteria in their environment. The LuxS/AI-2 QS system, which uses AI-2 (autoinducer-2) as a signal molecule, has been identified in both Gram-negative and Gram-positive bacteria. As one of the important global regulatory networks in bacteria, it responds to fluctuations in the numbers of bacteria and regulates the expression of a number of genes, thus affecting cell behavior. We summarize here the known relationships between the LuxS/AI-2 system and drug resistance, discuss the inhibition of LuxS/AI-2 system as an approach to prevent bacterial resistance, and present new strategies for the treatment of drug-resistant pathogens.

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Tissue distribution of marbofloxacin was studied in pigs after a single intramuscular injection at 2.5 mg/kg body weight. Samples of plasma, muscle, liver, kidney, heart, lung, and muscle at the injection site were randomly collected from five pigs at 2, 6, 10, 24, 48, 72, and 96 h after administration. Marbofloxacin concentrations were determined by using high-performance liquid chromatography with ultraviolet detection and were subjected to non-compartmental analysis to obtain kinetic parameters. The elimination half-life (t1/2λz) of marbofloxacin at the injection site was 22.12 h, while those in kidney, plasma, liver, lung, heart, and muscle were 16.75, 21.48, 21.84, 24.00, 24.45, and 28.91 h, respectively. Areas under the concentration-time curve from 0 h to ∞ (AUC0–∞s) were calculated to be 31.17 h·µg·mL−1 for plasma and 32.97, 33.92, 34.78, 37.58, 42.02, and 98.80 h·µg·g−1 for heart, muscle, lung, liver, kidney, and injection site, respectively. The peak concentration (Cmax) of marbofloxacin was 1.62 µg/mL in plasma and 1.71, 1.74, 1.86, 1.93, 2.45, and 7.64 µg/g in heart, lung, muscle, kidney, liver, and injection site, respectively. The results show that marbofloxacin was fast absorbed, extensively distributed, and slowly eliminated from pigs after a single intramuscular administration.

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The pharmacokinetic profiles of florfenicol (FF) or florfenicol amine (FFA) in crucian carp were compared at different water temperatures after single intramuscular administration of FF at 10 mg/kg bodyweight. The concentrations of FF and FFA were determined by a high-performance liquid chromatography method, and then, the concentration versus time data were subjected to compartmental analysis using a one-compartment open model. At the water temperatures of 10, 20, and 25°C, the peak concentrations (C s) of FF were 2.28, 2.29, and 2.34 μg/ml, respectively, while those of FFA were 0.42, 0.71, and 0.82 μg/ml, respectively. And the absorption half-life (t ) of FF was 0.21, 0.19, and 0.21 hr, while the elimination half-life (t ) was 31.66, 24.77, and 21.48 hr, respectively. For FFA, the formation half-life (t ) was 3.85, 8.97, and 12.43 hr, while the t was 58.34, 30.27, and 21.22 hr, respectively. The results presented here demonstrated that the water temperature had effects on the elimination of both FF and FFA and the formation of FFA. Based on the T > MIC values calculated here, to treat the infections of bacterial with MIC value ≤ 0.5 μg/ml, FF intramuscularly given at 10 mg/kg bodyweight with a 72-hr interval is sufficient at the water temperature of 10°C, while the intervals of 60 and 48 hr were needed at 20 and 25°C, respectively. But to treat bacterial with higher MIC values, more FF or FF at 10 mg/kg BW but with shorter intervals should be intramuscularly given to the infected fish.

The stratification of cancer into subtypes that are significantly associated with clinical outcomes is beneficial for targeted prognosis and treatment. In this study, we integrated somatic mutation and gene expression data to identify clusters of patients. In contrast to previous studies, we constructed cancer-type-specific significant co-expression networks (SCNs) rather than using a fixed gene network across all cancers, such as the network-based stratification (NBS) method, which ignores cancer heterogeneity. For each type of cancer, the gene expression data were used to construct the SCN network, while the gene somatic mutation data were mapped onto the network, propagated, and used for further clustering. For the clustering, we adopted an improved network-regularized non-negative matrix factorization (netNMF) (netNMF_HC) for a more precise classification. We applied our method to various datasets, including ovarian cancer (OV), lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC) cohorts derived from the TCGA (The Cancer Genome Atlas) project. Based on the results, we evaluated the performance of our method to identify survival-relevant subtypes and further compared it to the NBS method, which adopts priori networks and netNMF algorithm. The proposed algorithm outperformed the NBS method in identifying informative cancer subtypes that were significantly associated with clinical outcomes in most cancer types we studied. In particular, our method identified survival-associated UCEC subtypes that were not identified by the NBS method. Our analysis indicated valid subtyping of patient could be applied by mutation data with cancer-type-specific SCNs and netNMF_HC for individual cancers because of specific cancer co-expression patterns and more precise clustering.

Streptococcus suis serotype 2 ( S. suis 2) is a zoonotic pathogen. It causes meningitis, arthritis, pneumonia and sepsis in pigs, leading to extremely high mortality, which seriously affects public health and the development of the pig industry. Pyruvate dehydrogenase (PDH) is an important sugar metabolism enzyme that is widely present in microorganisms, mammals and higher plants. It catalyzes the irreversible oxidative decarboxylation of pyruvate to acetyl-CoA and reduces NAD+ to NADH. In this study, we found that the virulence of the S. suis ZY05719 sequence type 7 pdh deletion strain (Δ pdh ) was significantly lower than the wild-type strain (WT) in the mouse infection model. The distribution of viable bacteria in the blood and organs of mice infected with the Δ pdh was significantly lower than those infected with WT. Bacterial survival rates were reduced in response to temperature stress, salt stress and oxidative stress. Additionally, compared to WT, the ability to adhere to and invade PK15 cells, biofilm formation and stress resistance of Δ pdh were significantly reduced. Moreover, real-time PCR results showed that pdh deletion reduced the expression of multiple adhesion-related genes. However, there was no significant difference in the correlation biological analysis between the complemented strain (CΔ pdh ) and WT. Moreover, the survival rate of Δ pdh in RAW264.7 macrophages was significantly lower than that of the WT strain. This study shows that PDH is involved in the pathogenesis of S. suis 2 and reduction in virulence of Δ pdh may be related to the decreased ability to resist stress of the strain.