Current Issue : October - December Volume : 2013 Issue Number : 4 Articles : 7 Articles
Background: Lactobacillus species can contribute positively to general and oral health and are frequently acquired\r\nby breastfeeding in infancy. The present study aimed to identify oral lactobacilli in breast and formula-fed 4 monthold\r\ninfants and to evaluate potential probiotic properties of the dominant Lactobacillus species detected. Saliva and\r\noral swab samples were collected from 133 infants who were enrolled in a longitudinal study (n=240) examining\r\nthe effect of a new infant formula on child growth and development. Saliva was cultured and Lactobacillus isolates\r\nwere identified from 16S rRNA gene sequences. Five L. gasseri isolates that differed in 16S rRNA sequence were\r\ntested for their ability to inhibit growth of selected oral bacteria and for adhesion to oral tissues. Oral swab samples\r\nwere analyzed by qPCR for Lactobacillus gasseri.\r\nResults: 43 (32.3%) infants were breastfed and 90 (67.7%) were formula-fed with either a standard formula (43 out\r\nof 90) or formula supplemented with a milk fat globule membrane (MFGM) fraction (47 out of 90). Lactobacilli were\r\ncultured from saliva of 34.1% breastfed infants, but only in 4.7% of the standard and 9.3% of the MFGM\r\nsupplemented formula-fed infants. L. gasseri was the most prevalent (88% of Lactobacillus positive infants) of six\r\nLactobacillus species detected. L. gasseri isolates inhibited Streptococcus mutans binding to saliva-coated\r\nhydroxyapatite, and inhibited growth of S. mutans, Streptococcus sobrinus, Actinomyces naeslundii, Actinomyces oris,\r\nCandida albicans and Fusobacterium nucleatum in a concentration dependent fashion. L. gasseri isolates bound to\r\nparotid and submandibular saliva, salivary gp340 and MUC7, and purified MFGM, and adhered to epithelial cells.\r\nL. gasseri was detected by qPCR in 29.7% of the oral swabs. Breastfed infants had significantly higher mean DNA\r\nlevels of L. gasseri (2.14 pg/uL) than infants fed the standard (0.363 pg/uL) or MFGM (0.697 pg/uL) formula.\r\nConclusions: Lactobacilli colonized the oral cavity of breastfed infants significantly more frequently than formulafed\r\ninfants. The dominant Lactobacillus was L. gasseri, which was detected at higher levels in breastfed than\r\nformula-fed infants and displayed probiotic traits in vitro....
Background: Monoclonal antibody therapeutics are rapidly gaining in popularity for the treatment of a myriad of\r\ndiseases, ranging from cancer to autoimmune diseases and neurological diseases. Multiple forms of antibody\r\ntherapeutics are in use today that differ in the amount of human sequence present in both the constant and\r\nvariable regions, where antibodies that are more human-like usually have reduced immunogenicity in clinical trials.\r\nResults: Here we present a method to quantify the humanness of the variable region of monoclonal antibodies\r\nand show that this method is able to clearly distinguish human and non-human antibodies with excellent\r\nspecificity. After creating and analyzing a database of human antibody sequences, we conducted an in-depth\r\nanalysis of the humanness of therapeutic antibodies, and found that increased humanness score is correlated with\r\ndecreased immunogenicity of antibodies. We further discovered a surprisingly similarity in the immunogenicity of\r\nfully human antibodies and humanized antibodies that are more human-like based on their humanness score.\r\nConclusions: Our results reveal that in most cases humanizing an antibody and confirming the humanness of the\r\nfinal form may be sufficient to eliminate immunogenicity issues to the same extent as using fully human\r\nantibodies. We created a public website to calculate the humanness score of any input antibody sequence based\r\non our human antibody database. This tool will be of great value during the preclinical drug development process\r\nfor new monoclonal antibody therapeutics...
The antibacterial efficiency of various solvent extracts of sea grass root (Cymodocea serrulata) was observed against some human urinary tract infecting clinical bacterial species of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris and Pseudomonas aeruginosa. Fresh sea grass was collected from Mallipattinam coast, south east coast of India and crude extract were prepared by using three different solvent namely ethanol, methanol and acetone. The antibacterial activity was estimated by agar diffusion technique method. In addition to that, the minimum inhibitory concentration (MIC) was determined for C. serrulata extracts derived from three solvent with each pathogenic species and it was compared with an appropriate positive control. Among the three solvent extract the maximum activity (11.83±0.28 mm) showed against P. vulgaris in methanol extract and minimum activity of (1.66±0.57 mm), was shown against Escherichia coli in acetone extract. The next maximum activity was seen against P. mirabilis in same methanol solvents. The present study reveals that the activities of methanol extracts of sea grass C. serrulata was higher than that of ethanol and acetone extracts, against UTI pathogens....
Background: Antibiotic therapy can select for small colony variants of Staphylococcus aureus that are more\r\nresistant to antibiotics and can result in persistent infections, necessitating the development of more effective\r\nantimicrobial strategies to combat small colony variant infections. Photodynamic therapy is an alternative\r\ntreatment approach which utilises light in combination with a light-activated antimicrobial agent to kill bacteria\r\nvia a non-specific mechanism of action. In this study, we investigated whether the combination of 665 nm laser\r\nlight and the light-activated antimicrobial agent methylene blue was able to successfully kill S. aureus small colony\r\nvariants. S. aureus and isogenic stable small colony variant were exposed to varying doses (1.93 to 9.65 J/cm2) of\r\n665 nm laser light in the presence of varying concentrations (1 to 20 �µM) of methylene blue.\r\nResults: The combination of 665 nm laser light and methylene blue was found to be an effective strategy for the\r\nkilling of small colony variants. At the highest light dose (9.65 J/cm2) and methylene blue concentration (20 �µM) tested,\r\nthe number of viable bacteria decreased by approximately 6.9 log10 for the wild type and approximately 5 log10 for the\r\nsmall colony variant.\r\nConclusions: These results suggest that photodynamic therapy has potential for use in the treatment of superficial\r\ninfections caused by small colony variants of S. aureus and supports further research in this field....
Background: Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium\r\ntuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds\r\ncalled virulence factors to subvert human host defences and damage and invade the human host. Among these\r\nvirulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of\r\nM. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor.\r\nHere we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined\r\nthe genes whose expression is in vitro regulated by this transcriptional repressor.\r\nResults: We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv.\r\nAlthough we found equivalent replication of the Mt?mce2R mutant and the wild type strains in mouse lungs,\r\noverexpression of Mce2R in the complemented strain (Mt?mce2RComp) significantly impaired its replication.\r\nDuring in vitro infection of macrophages, we observed a significantly increased association of the late endosomal\r\nmarker LAMP-2 to Mt?mce2RComp-containing phagosomes as compared to Mt?mce2R and the wild type strains.\r\nWhole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the\r\nin vitro conditions studied.\r\nConclusions: The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the\r\nmce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest\r\nof phagosome maturation induced by M. tuberculosis....
Background: The yeast Saccharomyces cerevisiae can be a useful model for studying cellular mechanisms related to\r\nsterol synthesis in humans due to the high similarity of the mevalonate pathway between these organisms. This\r\nmetabolic pathway plays a key role in multiple cellular processes by synthesizing sterol and nonsterol isoprenoids.\r\nStatins are well-known inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the\r\ncholesterol synthesis pathway. However, the effects of statins extend beyond their cholesterol-lowering action, since\r\ninhibition of HMGR decreases the synthesis of all products downstream in the mevalonate pathway. Using\r\ntransgenic yeast expressing human HMGR or either yeast HMGR isoenzyme we studied the effects of simvastatin,\r\natorvastatin, fluvastatin and rosuvastatin on the cell metabolism.\r\nResults: Statins decreased sterol pools, prominently reducing sterol precursors content while only moderately\r\nlowering ergosterol level. Expression of genes encoding enzymes involved in sterol biosynthesis was induced, while\r\ngenes from nonsterol isoprenoid pathways, such as coenzyme Q and dolichol biosynthesis or protein prenylation,\r\nwere diversely affected by statin treatment. Statins increased the level of human HMGR protein substantially and\r\nonly slightly affected the levels of Rer2 and Coq3 proteins involved in non-sterol isoprenoid biosynthesis.\r\nConclusion: Statins influence the sterol pool, gene expression and protein levels of enzymes from the sterol and\r\nnonsterol isoprenoid biosynthesis branches and this effect depends on the type of statin administered. Our model\r\nsystem is a cheap and convenient tool for characterizing individual statins or screening for novel ones, and could\r\nalso be helpful in individualized selection of the most efficient HMGR inhibitors leading to the best response and\r\nminimizing serious side effects....
Background: Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and\r\nsoft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of\r\ntoxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus\r\nstrains isolated from skin, soft tissue, and bone related infections.\r\nResults: A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis,\r\nabscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were\r\nresistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin.\r\nPanton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by\r\nstaphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in\r\nisolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (=1%).\r\nConclusions: This study provides new insight into the prevalence of toxin and antibiotic resistance genes in\r\nS. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly\r\nassociated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections\r\nin Benin....
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