Genetic Determinants of Salmonella Resistance to the Biofilm-Inhibitory Effects of a Synthetic 4-Oxazolidinone Analog
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
Authors: Griewisch, K. F.; Pierce, J. G.; Elfenbein, J. R.
Abstract
Biofilms formed by Salmonella enterica are a frequent source of food supply contamination. Since biofilms are inherently resistant to disinfection, new agents capable of preventing biofilm formation are needed. Synthetic analogs of 4-oxazolidinone containing natural products have shown promise as antibiofilm compounds against Gram-positive bacteria. The purpose of our study was 2-fold: to establish the antibiofilm effects and mechanism of action of a synthetic 4-oxazolidinone analog (JJM-ox-3-70) and to establish mechanisms of resistance to this compound in Salmonella enterica serovar Typhimurium (S. Typhimurium). JJM-ox-3-70 inhibited biofilm formation but had no effect on cell growth. The antibiofilm effects were linked to disruption of curli fimbriae and flagellar gene expression and alteration in swimming motility, suggesting an effect on multiple cellular processes. Using a 2-step screening approach of defined multigene and single-gene deletion mutant libraries, we identified 3 mutants that produced less biofilm in the presence of JJM-ox-3-70 than the isogenic WT, with phenotypes reversed by complementation in trans. Genes responsible for S. Typhimurium resistance to the compound included acrB, a component of the major drug efflux pump AcrAB-TolC, and two genes of unknown function (STM0437 and STM1292). The results of this study suggest that JJM-ox-3-70 inhibits biofilm formation by indirect inhibition of extracellular matrix production that may be linked to disruption of flagellar motility. Further work is needed to establish the role of the newly characterized genes as potential mechanisms of biofilm intrinsic antimicrobial resistance. IMPORTANCE Biofilms are resistant to killing by disinfectants and antimicrobials. S. enterica biofilms facilitate long-term host colonization and persistence in food processing environments. Synthetic analogs of 4-oxazolidinone natural products show promise as antibiofilm agents. Here, we show that a synthetic 4-oxazolidinone analog inhibits Salmonella biofilm through effects on both motility and biofilm matrix gene expression. Furthermore, we identify three genes that promote Salmonella resistance to the antibiofilm effects of the compound. This work provides insight into the mechanism of antibiofilm effects of a synthetic 4-oxazolidinone analog in Gramnegative bacteria and demonstrates new mechanisms of intrinsic antimicrobial resistance in Salmonella biofilms.
One-pot synthesis of multi-functional cellulose-based ionic conductive organohydrogel with low-temperature strain sensitivity
CARBOHYDRATE POLYMERS
Authors: You, Zhenping; Dong, Yue; Li, Xinghui; Yang, Pei; Luo, Min; Zhu, Ziqi; Wu, Leyang; Zhou, Xiaoyan; Chen, Minzhi
Abstract
The advent of high-performance conductive organohydrogels, which are sustainable in extremely cold environment, has attracted immersing interest in biosensors. In this work, a highly stretchable, self-healable, adhesive and antibacterial cellulose-based ionic conductive organohydrogel with low-temperature strain sensitivity was developed, using in-situ polymerization of acrylamide in glycerol-water with poly (vinyl alcohol), chitosan, FeCl3 and 2,2,6,6-Tetramethylpiperidine-1-oxyl oxidized cellulose nanofibril (TCNF). Owing to their chemically cross-linked structures and multiple H-bonding networks, the organohydrogel exhibits excellent mechanical properties, such as high stretchability (540 %), high compression strength (0.44 MPa), nearly 87 % self-healing efficiency and adhesive to various substrates. Also, good antibacterial property was confirmed by the diameter of inhibition zone (similar to 5.1 mm) against Salmonella enteritidis. Notably, the organohydrogels remained high conductivity and flexibility even below -20 degrees C, which can be applied as low-temperature strain sensor for real-time. Therefore, it has promising applications in artificial intelligence and personal healthcare under cold environment.