ABSTRACT
Four compounds, R3PAu[S2CN(CH2CH2OH)2], R=Ph (1) and cyclohexyl (2), and Et3PAuS2CNRê2, Rê=Rê=Et (3) and Rê2=(CH2)4 (4), have been evaluated for antibacterial activity against a panel of 24 Gram positive (8) and Gram negative (16) bacteria. Based on minimum inhibitory concentration (MIC) scores, compounds 1 and 2 were shown to be specifically potent against Gram positive bacteria whereas compounds 3 and, to a lesser extent, 4 exhibited broad range activity. All four compounds were active against methicillin resistant Staphylococcus aureus (MRSA). Time kill assays revealed the compounds to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Each compound was bactericidal against one or more bacteria with 3 being especially potent after 8h exposure; compounds 1 and 3 were bactericidal against MRSA. Compound 3 was the most effective bactericide across the series especially toward B. subtilis, S. saprophyticus, A. hydrophila, P. vulgaris, and V. parahaemolyticus. This study demonstrates the potential of this class of compounds as antibacterial agents, either broad range or against specific bacteria.
Subject(s)
Anti-Bacterial Agents , Gram-Positive Bacteria/growth & development , Organogold Compounds , Thiocarbamates , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Organogold Compounds/chemical synthesis , Organogold Compounds/chemistry , Organogold Compounds/pharmacology , Thiocarbamates/chemical synthesis , Thiocarbamates/chemistry , Thiocarbamates/pharmacologyABSTRACT
Salmonella is an important food-borne pathogen causing disease in humans and animals worldwide. Salmonellosis may be caused by any one of over 2,500 serovars of Salmonella. Nonetheless, Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Agona are the second most prevalent serovars isolated from humans and livestock products respectively. Limited knowledge is available about the virulence mechanisms responsible for diarrheal disease caused by them. To investigate the contribution of sopB, sopD and pipD as virulence factors in intracellular infections and the uniqueness of these bacteria becoming far more prevalent than other serovars, the infection model of Caenorhabditis elegans and phenotypic microarray were used to characterize their mutants. The strains containing the mutation in sopB, sopD and pipD genes were constructed by using latest site-specific group II intron mutagenesis approach to reveal the pathogenicity of the virulence factors. Overall, we observed that the mutations in sopB, sopD and pipD genes of both serovars did not exhibit significant decrease in virulence towards the nematode. This may indicate that these virulence effectors may not be universal virulence factors involved in conserved innate immunity. There are significant phenotypic differences amongst strains carrying sopB, sopD and pipD gene mutations via the analysis of biochemical profiles of the bacteria. Interestingly, mutant strains displayed different susceptibility to chemical stressors from several distinct pharmacological and structural classes when compared to its isogenic parental strains. These metabolic and chemosensitivity assays also revealed multiple roles of Salmonella virulence factors in nutrient metabolism and antibiotic resistance.
Subject(s)
Bacterial Proteins/metabolism , Salmonella enterica/pathogenicity , Virulence Factors/metabolism , Animals , Bacterial Proteins/genetics , Bacterial Typing Techniques , Caenorhabditis elegans/microbiology , Caenorhabditis elegans/physiology , Disease Models, Animal , Gene Knockout Techniques , Metabolic Networks and Pathways , Salmonella Infections/microbiology , Salmonella Infections, Animal/microbiology , Salmonella enterica/genetics , Salmonella enterica/isolation & purification , Serogroup , Virulence Factors/geneticsABSTRACT
The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
Subject(s)
Antineoplastic Agents/pharmacology , Organogold Compounds/pharmacology , Phosphines/chemistry , Thiocarbamates/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Death/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Models, Molecular , Molecular Structure , Organogold Compounds/chemical synthesis , Organogold Compounds/chemistry , Structure-Activity RelationshipABSTRACT
Garcinia is commonly found in Malaysia, but limited information is available regarding endophytic fungi associated with this plant. In this study, 24 endophytic fungi were successfully recovered from different parts of two Garcinia species. Characterization of endophytic fungi was performed based on the conserved internal transcribed spacer (ITS) region sequence analysis and the antimicrobial properties. Results revealed that fruits of the plant appeared to be the highest inhabitation site (38 %) as compared with others. Glomerella sp., Guignardia sp., and Phomopsis sp. appeared to be the predominant endophytic fungi group in Garcinia mangostana and Garcinia parvifolia. Phylogenetic relationships of the isolated endophytic fungi were estimated from the sequences of the ITS region. On the other hand, antibacterial screening showed 11 of the isolates possessed positive response towards pathogenic and nonpathogenic bacteria. However, there was no direct association between certain antibacterial properties with the specific genus observed.
Subject(s)
Ascomycota/genetics , Garcinia/microbiology , Ascomycota/isolation & purification , Base Sequence , DNA, Fungal/chemistry , DNA, Fungal/genetics , DNA, Ribosomal Spacer/chemistry , DNA, Ribosomal Spacer/genetics , Genetic Variation , Microbial Sensitivity Tests , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Sequence Alignment , SymbiosisABSTRACT
The increased occurrence of Salmonella occurrence in local indigenous vegetables and poultry meat can be a potential health hazards. This study is aimed to detect the prevalence of twenty different virulence factors among Salmonella enterica strains isolated from poultry and local indigenous vegetables in Malaysia via an optimized, rapid and specific multiplex PCR assay. The assay encompasses a total of 19 Salmonella pathogenicity islands genes and a quorum sensing gene (sdiA) in three multiplex reaction sets. A total of 114 Salmonella enterica isolates belonging to 38 different serovars were tested. Each isolate in under this study was found to possess up to 70% of the virulence genes tested and exhibited variable pathogenicity gene patterns. Reproducibility of the multiplex PCR assay was found to be 100% and the detection limit of the optimized multiplex PCR was tested with lowest detectable concentration of DNA 0.8 pg microl(-1). This study demonstrated various Salmonella pathogenicity island virulence gene patterns even within the same serovar. This sets of multiplex PCR system provide a fast and reliable typing approach based on Salmonella pathogenicity islands, thus enabling an effective monitoring of emerging pathogenic Salmonella strains as an additional tool in Salmonella surveillance studies.
