Resistance or decreased susceptibility to glycopeptides, daptomycin, and linezolid in methicillin-resistant Staphylococcus aureus

Nannini, Esteban C.; Murray, Barbara E.; Arias, César A.

doi:10.1016/j.coph.2010.06.006

Cited by 154 publications

(93 citation statements)

References 54 publications

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“…3 MRSA is resistant to all known β-lactam antibiotics, and reduced susceptibility to last-line antibiotics such as vancomycin, linezolid and daptomycin has also been reported. 4 …”

Section: Introductionmentioning

confidence: 99%

Structural investigation of humanS. aureus-targeting antibodies that bind wall teichoic acid

Fong¹,

Kajihara²,

Chen³

et al. 2018

mAbs

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Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a growing health threat worldwide. Efforts to identify novel antibodies that target S. aureus cell surface antigens are a promising direction in the development of antibiotics that can halt MRSA infection. We biochemically and structurally characterized three patient-derived MRSA-targeting antibodies that bind to wall teichoic acid (WTA), which is a polyanionic surface glycopolymer. In S. aureus, WTA exists in both α- and β-forms, based on the stereochemistry of attachment of a N-acetylglucosamine residue to the repeating phosphoribitol sugar unit. We identified a panel of antibodies cloned from human patients that specifically recognize the α or β form of WTA, and can bind with high affinity to pathogenic wild-type strains of S. aureus bacteria. To investigate how the β-WTA specific antibodies interact with their target epitope, we determined the X-ray crystal structures of the three β-WTA specific antibodies, 4462, 4497, and 6078 (Protein Data Bank IDs 6DWI, 6DWA, and 6DW2, respectively), bound to a synthetic WTA epitope. These structures reveal that all three of these antibodies, while utilizing distinct antibody complementarity-determining region sequences and conformations to interact with β-WTA, fulfill two recognition principles: binding to the β-GlcNAc pyranose core and triangulation of WTA phosphate residues with polar contacts. These studies reveal the molecular basis for targeting a unique S. aureus cell surface epitope and highlight the power of human patient-based antibody discovery techniques for finding novel pathogen-targeting therapeutics.

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“…3 MRSA is resistant to all known β-lactam antibiotics, and reduced susceptibility to last-line antibiotics such as vancomycin, linezolid and daptomycin has also been reported. 4 …”

Section: Introductionmentioning

confidence: 99%

Structural investigation of humanS. aureus-targeting antibodies that bind wall teichoic acid

Fong¹,

Kajihara²,

Chen³

et al. 2018

mAbs

View full text Add to dashboard Cite

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“…Nonsusceptibility to daptomycin has also been associated with changes in the structure and function of the cell envelope and surface charge. Linezolid resistance is associated with mutations in the 23S rRNA, although acquired resistance has now been documented (Nannini et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

PREVALENCE OF HETEROGENEOUS GLYCOPEPTIDE INTERMEDIATE RESISTANCE IN METHICILLIN-RESISTANT <i>STAPHYLOCOCCUS AUREUS</i>

Chaudhary¹

2013

American Journal of Infectious Diseases

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Multidrug resistant Methicillin-Resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial and community acquired infections and is on the rise. The aim of this investigation was to explore the prevalence of MRSA and heterogeneous Glycopeptide Intermediate Staphylococcus aureus (hGISA) in various clinical samples, to investigate the various antibiotic resistant determinant genes among these strains collected from north and west Indian hospitals and to evaluate the response of various drugs to these strains. A total of 413 clinical specimens collected from different hospitals were processed for the screening of S. aureus and MRSA. All the MRSA strains were further screened for hGISA on Mueller-Hinton agar containing 8 µg mL −1 teicoplanin or 6 µg mL −1 vancomycin. hGISA confirmed by the E-test method with a dense inoculum and a simplified method of population analysis. Susceptibility study was conducted according to the Clinical and Laboratory Standards Institute (CLSI) methods. Among 211/413 S. aureus clinical isolates, 61.6% (130/211) of the isolates were confirmed to be MRSA which included maximum isolates from pus, blood, urine, wound swab and ear swab samples in decreasing order. hGISA strains were found in 8/130 (6.1%) isolates. Vancoplus, a novel antibiotic adjuvant entity was found to be susceptible in 96.1 to 97.8% MRSA strains and showed intermediate response in 2.2 to 3.8% of isolates. Linezolid appeared to be second most active antibiotic with 48.0 to 81.2% susceptibility, followed by teicoplanin (41.3 to 56.2% susceptibility). There was 8.7 to 9.6% resistance observed in Linezolid which was increased to 48% in teicoplanin, to >60% in daptomycin and >75% in vancomycin. Interestingly, none of the isolates were susceptible to ceftriaxone and cefoperazone plus sulbactam. From the above study it can be concluded that prevelance of MRSA has reached a significant level and Vancoplus is the most effective drug in MRSA as well as hGISA organisms in comparison to comparator drugs.

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“…Many of the reported cases of infections caused by linezolid-resistant MRSA have been associated with deep organ, foreign body, nosocomial outbreaks, and/or prolonged therapy with Linezolid (usually more than three weeks) [14,46].…”

Section: Linezolid On Treatment Of Multiresistant Bacteriamentioning

confidence: 99%

“…Mutations associated with ribosomal proteins also affect the activity of linezolid. It has recently been discovered that an RNA methyltransferase, called Cfr, is the cause of a new phenotype of resistance to phenicols and clindamycin, which also confers resistance to oxazolidinones) [14,46].…”

Section: Linezolid On Treatment Of Multiresistant Bacteriamentioning

confidence: 99%

“…Most of reported cases have been associated with deep organ infections, presence of foreign body, nosocomial outbreaks and/or prolonged therapy with linezolid (for more than three weeks) [14]. The mechanism of resistance to linezolid most described is the specific nucleotides substitution in rRNA 73, being the number of genes mutated is related to the level of resistance to the drug.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Linezolid use in Medicin Therapy against Multiresistant Bacteria-A Review

Mendes¹,

Costa²,

Paulino³

et al. 2017

J Bacteriol Parasitol

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After the description of an element with ability to combat the infectious processes originating from bacteria, starts a race for survival between the interrelationship of species, bacterial and human. With the evolution scientifictechnical, the man was able to synthesize new antibacterial substances, on the other hand the mechanisms of gene evolution enabled the emergence of multidrug-resistant bacteria. Some of this organisms are frequent on hospital environment and have high adaptability to new drugs, such as Staphylococcus aureus and Enterococcus spp. resistant to oxacillin and vancomycin, considered drugs of choice against multidrug-resistant microorganisms. So, a new antibiotics class was developed, superior to vancomycin and oxazolidinone, the linezolid. Thus, the present study aimed at understanding the use of linezolid in drug therapy against multi-resistant bacteria. To perform this study, a literature review of last 10 years was performed. In 2002, after the liberation of the use of linezolid as treatment for infectious processes against gram-positive bacteria, this drug was commonly used throughout the world. Similarly, the pressure of natural selection stood out, and there were records of resistant strains to linezolid. As prospects for control of infections caused by these resistant strains, was approved by the FDA in 2014 the use of drugs with linezolid resistant anti-strains activity. However, we conclude that, in addition to natural selection and genetic variation process, human behavior regarding the use of antibiotics, increases the selection of resistant microorganisms to antibiotic, including linezolid.

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Resistance or decreased susceptibility to glycopeptides, daptomycin, and linezolid in methicillin-resistant Staphylococcus aureus

Cited by 154 publications

References 54 publications

Structural investigation of humanS. aureus-targeting antibodies that bind wall teichoic acid

Structural investigation of humanS. aureus-targeting antibodies that bind wall teichoic acid

PREVALENCE OF HETEROGENEOUS GLYCOPEPTIDE INTERMEDIATE RESISTANCE IN METHICILLIN-RESISTANT <i>STAPHYLOCOCCUS AUREUS</i>

Linezolid use in Medicin Therapy against Multiresistant Bacteria-A Review

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