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Mechanism of Drug Resistance in Staphylococcus aureus and Future Drug Discovery
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Felipe Wakasuqui, Ana Leticia Gori Lusa, Sven Falke, Christian Betzel, Carsten Wrenger
To treat S. aureus also lipopeptide antibiotics are applied today. These peptides have a lipid moiety attached. One member of this class, daptomycin, is a cyclic lipopeptide used to treat infections against Gram-positive bacteria, except pulmonary infections, since it is inactivated by surfactant. Daptomycin interacts with calcium in an equimolar manner; and the calcium daptomycin complex can interact with phosphatidylglycerol or cardiolipin of the cell membrane, where it aggregates and creates distortions, leading to leakage of ions and depolarization (Straus and Hancock, 2006). The mechanism of the cell death is not completely understood yet. Resistance to Daptomycin is associated with a gain of function single nucleotide polymorphisms in the multipeptide resistance factor gene (mprF), which is responsible for the lysinylation of lysyl-phosphatidylglycerol and its inner to outer cell membrane translocation, which generates a more positively charged surface (Bayer et al., 2012). Several other modifications of cell membrane confer resistance to daptomycin, as well changes in genes that confer resistance to damage against the envelop (Miller et al., 2016). There is a correlation between reduced daptomycin susceptibility and the VISA phenotype due to an increase in the thickness of cell wall (Cui et al., 2006).
Research Progress in Synthesization, Coating, and Characterization of Magnetic Nanoparticles
Published in Francisco Torrens, A. K. Haghi, Tanmoy Chakraborty, Chemical Nanoscience and Nanotechnology, 2019
Lavanya Tandon, Poonam Khullar
Infectious bacterial diseases are the leading cause of disability and death,77 the majority of these infections are more prevalent in developing countries. Every year, approximately 17 million deaths are due to these infectious diseases and this represents one-third of global mortality. Infections due to gram-positive bacteria is the major cause of morbidity and mortality in humans.78,79 Such diseases can be treated by the ability to rapidly diagnose Gram-positive pathogens. Staphylococci and Streptococci are the most common Gram-positive pathogenic bacteria in human-sarecocci (sphere-shapedbacteria). Many antibiotics are being developed to treat Gram-positive infections. These antibiotics work by inhibiting cell wall synthesis or by blocking transcription/translation processes. Vancomycin is a glycopeptide which is composed of peptide sequence and glycosides. It is a commonly used antibiotic which results in inhibition of cell wall synthesis. The binding with the target bacteria takes place through the peptide. Vancomycin forms hydrogen bonds with the terminal D-alanyl-D-alanine (D-Ala-D-Ala) moieties of the N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) peptide subunits80,81 and exerts its antibacterial activity. Due to this binding, subunits cannot be incorporated into a major structural component of gram-positive cell walls and thus inhibition of cell wall takes place. New generation antibiotics that is, daptomycin, linezolide, and pristinamycin. Through hydrophobic tail, Daptomycin binds to the cell wall of gram-positive bacteria and results in perturbation and depolarization of the cell membrane.
Prevalence of virulence determinants and antibiotic resistance patterns of Enterococcus faecalis strains in patients with community-acquired urinary tract infections in Iran
Published in International Journal of Environmental Health Research, 2018
Abdullah Karimi, Zohreh Ghalavand, Fatemeh Fallah, Parisa Eslami, Mahmoud Parvin, Masoud Alebouyeh, Marjan Rashidan
With respect to antibiotic resistance, Table 2 indicates the results of antibiotic susceptibility test from 70 isolates of E. faecalis. In general, these results exhibited the highest resistance to tetracycline 62 (88.6%) and minocycline 61 (87.1%), while it was lower for gentamicin (120 µg) 12 (17.1%), ciprofloxacin 13 (18.6%), gatifloxacin 9 (12.9%), levofloxacin 9 (12.9%). Among all isolates, 69 (98.6%) of isolates were susceptible to vancomycin, ampicillin, penicillin, nitrofurantoin, and linezolid. MIC for vancomycin was ≥256 µg/ml. None of the 70 studied isolates exhibited resistance to daptomycin. In addition, tetracycline resistance determinant (tetM) was found in 66 (94.3%) of these isolates studied.