scholarly journals The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone

2022 ◽  
Vol 12 ◽  
Author(s):  
Lulu Zhang ◽  
Weifeng Yang ◽  
Yajun Chu ◽  
Bo Wen ◽  
Yungchi Cheng ◽  
...  

Methicillin-resistant Staphylococcus aureus (MRSA) is a superbacterium, and when it forms biofilms, it is difficult to treat even with the first-line of antibiotic linezolid (LNZ). Reyanning mixture (RYN), a compound-based Chinese medicine formula, has been found to have inhibitory effects on biofilms. This study aims to explore the synergistic inhibitory effect and corresponding mechanisms of their (LNZ&RYN) combination on the planktonic as well as biofilm cells of MRSA. Broth microdilution and chessboard methods were employed for the determination of minimum inhibitory concentrations (MICs) and synergistic concentration of LNZ&RYN, respectively. The effect of the combined medication on biofilm and mature biofilm of MRSA were observed by biofilm morphology and permeability experiments, respectively. To unveil the molecular mechanism of action of the synergistic combination of LNZ and RYN, RT-PCR based biofilm-related gene expression analysis and ultra-high pressure liquid chromatography-time-of-flight mass spectrometry based endogenous metabonomic analysis were deployed. The results indicated that 1/16RYN as the best combined dose reduced LNZ (4 μg/ml) to 2 μg/ml. The combined treatment inhibited living MRSA before and after biofilm formation, removed the residual structure of dead bacteria in MRSA biofilms and affected the shape and size of bacteria, resulting in the improvement of biofilm permeability. The mechanism was that biofilm-related genes such as agrC, atlA, and sarA, as well as amino acid uptake associated with the metabolism of 3-dehydrocarnitine, kynurenine, L-leucine, L-lysine and sebacic acid were inhibited. This study provides evidence for the treatment of MRSA and its biofilms with LNZ combined with RYN.

1987 ◽  
Vol 114 (4) ◽  
pp. 470-474 ◽  
Author(s):  
G. S. G. Spencer ◽  
D. J. Hill ◽  
G. J. Garssen ◽  
J. P. G. Williams

Abstract. The effects of somatostatin on the acute metabolic actions of insulin on newborn rat myoblasts in culture has been examined during monolayer culture. Somatostatin significantly inhibited the insulin-stimulated uptake of [3H]leucine and [3H]amino-isobutyric acid into myoblasts but had no effect on basal (unstimulated) uptake of these two substances. The lowest concentration of somatostatin to have a significant effect was 10 μg/l, and this was apparent in all the experiments undertaken. The inhibitory effect of somatostatin was seen at all effective concentrations of insulin used (0.3–1 U/l). These findings lend support to the concept of an endocrine role for somatostatin in vivo and suggest that a peripheral antagonism may exist between circulating insulin and somatostatin on anabolic processes such as nutrient uptake into cells.


1987 ◽  
Vol 252 (1) ◽  
pp. R78-R84
Author(s):  
J. K. Tews ◽  
J. Greenwood ◽  
O. E. Pratt ◽  
A. E. Harper

Passage of amino acids across the blood-brain barrier is assumed to be modified by amino acid composition of the blood. To gain a better understanding of the effects of protein intake on brain amino acid uptake, we examined associations among diet, plasma amino acid patterns, and the rate of entry of valine into the brain. Rats were fed (8 h/day for 7–10 days) diets containing 6, 18, or 50% casein before receiving one meal of a diet containing 0, 6, 18, or 50% casein. After 4–7 h, they were anesthetized and infused intravenously with [14C]valine for 5 min before plasma and brain samples were taken for determination of radioactivity and content of individual amino acids. As protein content of the meal was increased from 0 to 50% casein, plasma and brain concentrations of valine and most other large neutral amino acids (LNAA) increased severalfold; also the ratio of [14C]valine in brain to that in plasma decreased by greater than 50%, and the rate of valine entry into the brain increased 3.5-fold. The increase in valine flux slowed as plasma levels of LNAA, competitors for valine transport, increased. The results were far more dependent on protein content of the final meal than on that of the adaptation diet; thus changes in protein intake, as reflected in altered plasma amino acid patterns, markedly altered valine entry into the brain.


1984 ◽  
Vol 106 (1) ◽  
pp. 127-132 ◽  
Author(s):  
Ingrid Wiqvist ◽  
Anders Norström ◽  
Elizabeth O'Byrne ◽  
Nils Wiqvist

Abstract. Cervical tissue was obtained from women undergoing legal abortion in the 7th–15th week of gestation and tissue from the lower uterine segment was excised at elective Casearean section in the 38th–40th week. The specimens were incubated with [3H]proline in the presence of relaxin or prostaglandin E2 (PGE2). Relaxin had a concentration related inhibitory effect on the radiolabelling in the 7th–9th week but failed to influence the amino acid uptake in the 10th–15th week of pregnancy. PGE2 had the inverse effect, i.e. no influence in the former group but reduced incorporation of proline in the latter group of patients. Incubation of tissue from the lower uterine segment showed a similar response as that of the early pregnant cervix. It is concluded that relaxin has a significant influence on [3H]proline incorporation by cervical and uterine tissue under in vitro experimental conditions.


1997 ◽  
Vol 272 (1) ◽  
pp. C156-C162 ◽  
Author(s):  
E. Tsiani ◽  
N. Abdullah ◽  
I. G. Fantus

The protein tyrosine phosphatase (PTP) inhibitors vanadate and pervanadate (pV) exert insulin-like biologic effects. In cultured differentiated rat L6 skeletal muscle cells, vanadate and pV stimulated 2-deoxy-D-[3H]glucose uptake in a dose- and time-dependent manner. There was no increase in maximum stimulation by additional insulin. In contrast, whereas insulin stimulated [14C]methylaminoisobutyric acid (MeAIB) uptake, basal uptake was inhibited by vanadate and pV. Insulin-stimulated MeAIB uptake was also inhibited in a dose-dependent manner and completely abolished by 5 mM vanadate or 0.1 mM pV. The inhibitory effect on basal MeAIB uptake was associated with a decrease in transporter affinity and a small decrease in maximum transport capacity, whereas the insulin-stimulated increase in maximum transport capacity was completely inhibited. Inhibition of MeAIB uptake by vanadate and pV was not blocked by cycloheximide, and oubain did not inhibit uptake. Vanadate also inhibited amino acid deprivation-stimulated MeAIB uptake. Insulin-stimulated MeAIB uptake was also inhibited in rat hepatoma cells. Thus vanadate and pV mimic insulin to stimulate glucose uptake but inhibit system A amino acid uptake. The relative inhibitory concentrations of vanadate and pV suggest that the mechanism may involve PTP inhibition.


2001 ◽  
Vol 113 (3) ◽  
pp. 352-358 ◽  
Author(s):  
Jörgen Persson ◽  
Torgny Näsholm

2008 ◽  
Vol 57 (2) ◽  
pp. 151-158 ◽  
Author(s):  
Chunhong Shao ◽  
Qunye Zhang ◽  
Yundong Sun ◽  
Zhifang Liu ◽  
Jiping Zeng ◽  
...  

The ability of Helicobacter pylori to tolerate bile is likely to be important for its colonization and survival in the gastrointestinal tract of humans. As bile can be acidified after reflux into the low pH of the human stomach, the inhibitory effect of fresh human bile with normal appearance on H. pylori before and after acidification was tested first. The results showed that acidification of bile attenuated its inhibitory activity towards H. pylori. Next, the protein profiles of H. pylori under human bile and acidified bile stress were obtained by two-dimensional electrophoresis. Protein spots with differential expression were identified using tandem matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results showed that the changes in proteomic profiles under bile and acidified bile stress were similar when compared with that of normal H. pylori. Expression of 28 proteins was found to be modulated, with the majority being induced during bile or acidified bile exposure. These proteins included molecular chaperones, proteins involved in iron storage, chemotaxis protein, enzymes related to energy metabolism and flagellar protein. These results indicate that H. pylori responds to bile and acidified bile stress through multiple mechanisms involving many signalling pathways.


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