9-Apr-2018: Odilorhabdins; A new class of antibiotics discovered.
The spread of multidrug-resistant bacteria has prompted a renewed interest in antibiotics with novel chemical scaffolds and mechanisms of action. Scientists describe a previously unknown class of ribosome-targeting antibiotics, Odilorhabdins (ODLs). They reveal the binding site of ODLs in the decoding center of the small ribosomal subunit and show that these inhibitors render the ribosome error prone. Odilorhabdins exhibit bactericidal activity against Gram-positive and Gram negative pathogens and are able to cure bacterial infection in animal models.
- Odilorhabdins are a new class of naturally produced, ribosome-targeting antibiotics.
- ODLs bind to the small ribosomal subunit at a site not exploited by known antibiotics.
- ODLs induce miscoding, likely by increasing the affinity of aa-tRNAs to the ribosome.
- ODLs show promising antibacterial spectrum and efficacy in mouse infection models.
Odilorhabdins (ODLs), produced by the enzymes of the non-ribosomal peptide synthetase gene cluster of the nematode-symbiotic bacterium Xenorhabdus nematophila. ODLs show activity against Gram-positive and Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae, and can eradicate infections in animal models.
Typbar TCV is a vaccine containing polysaccharide of Salmonella typhi Ty2 conjugated to Tetanus Toxoid. Vi Capsular polysaccharide of Salmonella typhi alone elicit B cell responses, but the conjugation of bacterial polysaccharide to a protein carrier provides foreign peptide antigens that are presented to the immune system eliciting antigen-specific CD4+ Th cells, referred to as T-dependent antibody responses. A hallmark of T-dependent responses, which are also elicited by toxoid is to induce both higher-affinity antibodies and long-term immune memory.
Typbar TCV is the world’s first clinically proven conjugate Typhoid vaccine. Further, Typbar TCV is the only approved vaccine for children and infants less than 2 years of age. During the phase 3 clinical study, a single dose of Typbar TCV elicited 4-fold sero-conversion rates of 98.05%, 99.17% and 92.13% in subjects between ≥6 months to 2 years, ˃2 to 15 years and ˃15 to 45 years respectively. Results of this study were published in the Journal of Clinical Infectious Diseases.
Results from a human challenge study carried out at University of Oxford have demonstrated that the vaccine is safe, 100% immunogenic, and prevents up to 87.1% of infections, when using real life definitions of typhoid fever. Typbar TCV has been recommended by the experts at the WHO-Strategic Advisory Group for routine immunizations and is WHO prequalified.
18-Apr-2017: Anti-viral drug from frog mucus
Skin mucus secreted by a frog species found in Kerala can be used to develop an anti-viral drug that can treat various strains of flu. Frog mucus is loaded with molecules that kill bacteria and viruses and researchers are beginning to investigate it as a potential source for new anti-microbial drugs.
One of these “host defence peptides”, found in a frog species (Hydrophylax bahuvistara) native to Kerala can destroy many strains of human flu and protect mice against flu infection.
When researchers delivered small electric shocks, they collected the secretion that contained a peptide, or chain of amino acids, that appears to fight off the H1 strain of flu virus.
The researchers named the newly identified peptide “Urumin” after the urumi, a sword with a flexible blade that snaps and bends like a whip. Electron microscope images of the virus after exposure to Urumin reveal a virus that has been completely dismantled.
Urumin is not toxic to mammals, but “appears to only disrupt the integrity of flu virus”. When researchers squeezed some Urumin into the noses of lab mice, the peptide protected them against what would have otherwise been a lethal dose of H1 flu virus, the kind responsible for the 2009 swine flu pandemic.
It seems to work by binding to a protein that is identical across many influenza strains, and in lab experiments, it was able to neutralise dozens of flu strains, from the 1934 archival viruses up to modern ones.
More research is needed to determine if Urumin could become a preventive treatment against the flu in humans, and to see if other frog-derived peptides could protect against viruses like dengue and Zika.