A antibiotic that is Gram-negative-selective
Lol system inhibition in bacteria can lead to colonization resistance against Clostridium difficile and Escherichia coli: a first-principles study
Gram-negative bacteria include public-health villains such as Escherichia coli and Klebsiella pneumoniae. They can cause diseases that can include a potentially lethal immune-system response to infections.
To find a way around the bacteria’s defences, the study’s authors started with compounds that don’t kill the bacteria but are known to inhibit the ‘Lol system’, a group of proteins that is exclusive to Gram-negative bacteria. The researcher, Paul Hergenrother, a chemist at the University of Illinois at Urbana- Capita, says that the compound that yielded lolamicin was tinkered with.
The effects of antibiotics on the gut microbiota and colonization resistance against Clostridium difficile. mBio 6, e00974 (2015).
The study proves the viability of targeting the Lol system, but there is still a long road from showing efficacy in mice to developing a drug for human use.
Gram-negative-selective antibiotic that spares the gut microbiome: Comment on “Monte Carlo’s column on a recent census study” by A. Hiller, Phys. Lett.
Hiller also sounds a cautious note. There is not much money for a novel antibiotic since it takes more than two decades to get approved for clinical use. There are up to 20 new Gram-negative antibiotics discovered in the last ten years, but none has been approved by the FDA.
Clostridioides difficile colonization can be associated with antibiotic-specific changes. mSphere 6, e01238-20 (2021).
Parker, E. N. et al. Implementation of permeation rules leads to FabI inhibitor activity against Gram-negative pathogens. It is the Nat. Microbiol. 5, 67–75 (2020).
McMurdie, P.J. and Simpson, S. collaborated on an R package for interactive analysis and graphics of census data. PLoS ONE 8, e61217 (2013).
Lan, Y., Wang, Q., Cole, J. R. & Rosen, G. L. Using the RDP classifier to predict taxonomic novelty and reduce the search space for finding novel organisms. The paper named PLoS ONE 7, e32491.
Source: A Gram-negative-selective antibiotic that spares the gut microbiome
Constant-pressure molecular-dynamics simulation on heterogeneous biological membranes. J. Chem. Phys. B 113, 7830-7843 (2001)
Feller, S. E., Zhang, Y. H., Pastor, R. W. & Brooks, B. R. Constant-pressure molecular-dynamics simulation—the Langevin piston method. There is a J. Chem. Phys. 103 was published in 1995.
The equation of motion of a system with constraints has a numerical integration. J. Comput. Phys. 23, 327–341 (1977).
Klauda, J. B. et al. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J. Phys. Chem. B 114, 7830-7843 was published in 2010.
A novel by Hart, K. Optimization of the CHARMM additive force field for DNA: improved treatment of the BI/BII conformational equilibrium. J. Chem. Theor. Comput. 8 was published in 2012
New scoring function, efficientOptimizing and multithreading were some of the improvements made to the AutoDock Vina. J. Comput. Chem. 31, 455–46) was published in 2010.
Licari, G., Dehghani-Ghahnaviyeh, S. & Tajkhorshid, E. Membrane Mixer: a toolkit for efficient shuffling of lipids in heterogeneous biological membranes. J. Chem. Inform. Model. 62, 986–996 (2022).
Source: A Gram-negative-selective antibiotic that spares the gut microbiome
On the role of the iclaprim carrier protein reductase in countering Gram-negative antibiotic resistance. Theory and application to cell wall reporter acs
Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983).
Pandit, K. R. & Klauda, J. B. Membrane models of E. coli containing cyclic moieties in the aliphatic lipid chain. A person with a biological similarity to me. Biophys. Acta 1818, 1205–1210 (2012).
Rana, P. et al. FabI (enoyl acyl carrier protein reductase)—a potential broad spectrum therapeutic target and its inhibitors. Eur. J. Med. There are two Chem. 208, 112757 in 2020.
Lehman, K. M. & Grabowicz, M. Countering Gram-negative antibiotic resistance: recent progress in disrupting the outer membrane with novel therapeutics. Antibiotics 8, 163 (2019).
K. P. and Purnapatre collaborated on a paper. In vitro and in vivo activities of DS86760016, a novel leucyl-tRNA synthetase inhibitor for Gram-negative pathogens. Antimicrob. 63, e01987-18 et al.
C.Oefner et al. Increased hydrophobic interactions of iclaprim with Staphylococcus aureus dihydrofolate reductase are responsible for the increase in affinity and antibacterial activity. The Antimicrob is related to the Antimicrob. Chemother. 63, 687–698 (2009).
M.,Garcia Chavez and others. Synthesis of fusidic acid derivatives yields a potent antibiotic with an improved resistance profile. An infectious disease caused by the acs Infect. Dis. 7, 493–505 (2021).
A S., Nayar, and others were involved. The cell wall reporter assays show novel antibacterial targets. J. Bacteriol. A few years ago, 195, 1726–1734.
M. F. & Hergenrother are both related to P.J. It’s a challenge to convert Gram positive only compounds into broad-spectrum antibiotics. Ann. NY Acad. Sci. 1435, 18–38 (2019).
Source: A Gram-negative-selective antibiotic that spares the gut microbiome
Outer Membrane Targeting of Pseudomonas aeruginosa Proteins. mBio 2: a novel antibiotic target
The essential trafficking pathway for outer lipoproteins has been redefined. Proc. There is a Natl Acad. Sci. USA 114, 4769–4774 (2017).
Ito, H. et al. A new screening method to identify an antibiotic target, known as a novel antibacterial target. The person is a Microbiol. Immun. 51, 263–270 (2007).
H. H. et al. Outer membrane targeting of Pseudomonas aeruginosa proteins shows variable dependence on the components of Bam and Lol machineries. mBio 2 was released in 2011.
Source: A Gram-negative-selective antibiotic that spares the gut microbiome
Degradation and interactions of thiourea compounds with the lipoprotein targeting chaperone LolA. Bioorg. Med. Lett. 23, 2426-2431 (2013)
Barker, C. A. et al. Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA. Bioorg. Med. It’s Chem. Lett. 23, 2426–2431 (2013).
Polymyxins can be used to manage multi drug-resistant Gram-negative infections. Clin. Infect. Dis. 40, 1333–1341 was published in 2005.
Lagier, J.C., Million, M., Hugon, P., Armougom, F., and Noiret, D. discussed the human gut system. There is a front. Cell Infect. Microbiol. 2, 136 (2012).
Lofmark, Jernberg, C., Jansson, J. K. and Edlund studied the long-term persistence of resistant Bacteroides spp. A microbicidal agent. Chemother.
Scientists have identified an antibiotic compound that may be used to treat people infected with ‘Gram negative’ bacteria, including those with serious medical conditions. The compound was identified by studying the ‘Lol system’, a group of proteins that is exclusive to ‘Gram negative’ bacteria. “The compound has been found to be effective against Gram negative bacteria in mice,” researchers said.