LCB01-0371 is a new oxazolidinone with cyclic amidrazone. In vitro activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens. In vivo activity of LCB01-0371 against systemic infections in mice was also evaluated. LCB01-0371 was more active than linezolid against these systemic infections. LCB01-0371 showed bacteriostatic activity against Staphylococcus aureus.The emergence of multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MRCNS), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycinresistant enterococci (VRE), has generated worldwide concern in the medical community (11). The requirement for effective new antimicrobial agents to treat infections caused by Gram-positive organisms is becoming urgent as resistance to existing agents arises and spreads around the world.The oxazolidinones, a totally synthetic class of novel antibiotics, have strong activity against nearly all Gram-positive organisms, including those resistant to other agents (1, 10). They inhibit protein synthesis by binding to domain V of the 23S rRNA and thereby blocking formation of the initiation complex (6). Linezolid is the first member of the oxazolidinone class approved by the FDA in the United States. The success of linezolid and the occurrence of strains resistant to linezolid in clinical isolates of Enterococcus faecium (4, 5) and S. aureus (12) have inspired further efforts toward developing new oxazolidinones with improved safety and antibacterial activity.LCB01-0371 ( Fig. 1), a novel oxazolidinone with cyclic amidrazone, was synthesized by LegoChem BioSciences Inc. (Daejeon, Republic of Korea). In this study, in vitro activity of LCB01-0371 was compared with those of eight different antibacterial agents against 624 clinical isolates that were collected from several general hospitals in the Republic of Korea. In vivo activity of LCB01-0371 against systemic infections in mice and time-kill studies of LCB01-0371 against S. aureus giorgio (methicillin-susceptible S. aureus [MSSA]) and S. aureus p125 (MRSA) were also investigated.(This study was presented in part at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, 2009 [7].)In vitro MICs were determined by the 2-fold agar dilution method as described by the Clinical and Laboratory Standards Institute (CLSI) (3). Mueller-Hinton agar (MHA) medium was used for testing aerobic and facultative organisms. Streptococcus pneumoniae, Streptococcus pyogenes, and Moraxella catarrhalis were grown on Mueller-Hinton agar supplemented with 5% defibrinated sheep blood (Hanil Komed Ltd., Sungnam City, Republic of Korea). Mueller-Hinton agar supplemented with 3% Fildes enrichment (Oxoid Ltd., Basingstoke, Hampshire, England) was used for Haemophilus influenzae. Bacteria (10 4 to 10 5 CFU) were s...

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The efficacy of standard therapeutic strategies for Helicobacter pylori ( H. pylori ) infection is decreasing over time due to the emergence of drug-resistant strains. As an alternative, the present study investigated the capacity of Lactobacilllus paracasei ( L. paracasei ) HP7, isolated from kimchi, to inhibit H. pylori growth. The effects of L. paracasei HP7 on H. pylori adhesion and H. pylori -induced inflammation were examined in AGS human gastric adenocarcinoma epithelial cells and a mouse model of H. pylori SS1 infection. L. paracasei HP7 reduced H. pylori adhesion to AGS cells and suppressed the inflammatory response in infected cells by downregulating interleukin-8. H. pylori colonization in the stomach of C57BL/6 mice was demonstrated by rapid urease test, and results showed significant decrease in mice post-treated with L. paracasei HP7. Additionally, L. paracasei HP7 decreased gastric inflammation and epithelial lesions in the stomach of H. pylori -infected mice. These results demonstrate that L. paracasei HP7 treatment can inhibit H. pylori growth and is thus a promising treatment for patients with gastric symptoms such as gastritis that are caused by H. pylori infection.

Stress-induced depression and anxiety (DA) are closely connected to gastrointestinal inflammation and dysbiosis, which can suppress brain-derived neurotrophic factor (BDNF) in the brain. Herein, we isolated the BDNF expression-inducing probiotics Lactobacillus casei HY2782 and Bifidobacterium lactis HY8002 in lipopolysaccharide-stimulated SH-SY5Y cells. Then, we investigated the effects of HY2782, HY8002, anti-inflammatory L-theanine, and their supplement (PfS, probiotics-fermented L-theanine-containing supplement) on DA in mice exposed to restraint stress (RS) or the fecal microbiota of patients with inflammatory bowel disease and depression (FMd). Oral administration of HY2782, HY8002, or L-theanine alleviated RS-induced DA-like behaviors. They also decreased RS-induced hippocampal interleukin (IL)-1β and IL-6 levels, as well as NF-κB-positive cell numbers, blood corticosterone level, and colonic IL-1β and IL-6 levels and NF-κB-positive cell numbers. L-theanine more potently suppressed DA-like behaviors and inflammation-related marker levels than probiotics. However, these probiotics more potently increased RS-suppressed hippocampal BDNF level and BDNF+NeuN+ cell numbers than L-theanine. Furthermore, HY2782 and HY8002 suppressed RS-increased Proteobacteria and Verrucomicrobia populations in gut microbiota. In particular, they increased Lachnospiraceae and Lactobacillacease populations, which are closely positively associated with hippocampal BDNF expression, and suppressed Sutterellaceae, Helicobacteriaceae, Akkermansiaceae, and Enterobacteriaceae populations, which are closely positively associated with hippocampal IL-1β expression. HY2782 and HY8002 potently alleviated FMd-induced DA-like behaviors and increased FMd-suppressed BDNF, serotonin levels, and BDNF-positive neuronal cell numbers in the brain. They alleviated blood corticosterone level and colonic IL-1β α and IL-6 levels. However, L-theanine weakly, but not significantly, alleviated FMd-induced DA-like behaviors and gut inflammation. BDNF expression-inducing probiotic (HY2782, HY8002, Streptococcus thermophilus, and Lactobacillus acidophilus)-fermented and anti-inflammatory L-theanine-containing supplement PfS alleviated DA-like behaviors, inflammation-related biomarker levels, and gut dysbiosis more than probiotics or L-theanine. Based on these findings, a combination of BDNF expression-inducing probiotics with anti-inflammatory L-theanine may additively or synergistically alleviate DA and gut dysbiosis by regulating gut microbiota-mediated inflammation and BDNF expression, thereby being beneficial for DA.