Molecular Basis for the Role of
            <i>Staphylococcus aureus</i>
            Penicillin Binding Protein 4 in Antimicrobial Resistance

Navratna, Vikas; Nadig, Savitha; Sood, Varun; Prasad, K.; Arakere, Gayathri; Gopal, B.

doi:10.1128/jb.00822-09

Cited by 81 publications

(80 citation statements)

References 46 publications

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“…66 The top-ranked constituent was apigenin,7-O-beta-D-glucopyranoside (Table 4), a constituent of D. genkwa. According to our literature search, the effect of this compound on MRSA is unknown.…”

Section: Pbp4mentioning

confidence: 99%

“…It is popular for screening active compounds from medicinal plants for inhibition against pharmacological receptors. 30,31 Here, the crystal structures of two common MRSA inhibitory targets, PBP2a and PBP4, were obtained from the Protein Data Bank (PDB) with PDB codes 4CJN 32 and 3HUM, 33 respectively. The constituents of M. officinalis, V. officinalis, M. charantia, and D. genkwa were downloaded from the TCM Database@Taiwan (http:// tcm.cmu.edu.tw/), which covers more than 20,000 pure compounds isolated from 453 TCMs ingredients.…”

Section: 29mentioning

confidence: 99%

See 1 more Smart Citation

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study

Kuok

Hoi

et al. 2017

Exp Biol Med (Maywood)

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Antibiotic resistant is a well-known threat to global health and methicillin-resistant Staphylococcus aureus is one of the most significant ones. These resistant bacteria kill thousands of people every year and therefore a new effective antimicrobial treatment is necessary. This study identified the herbs and their associated bioactive ingredients that can potential the effects of current antibiotics. These herbs have long history of human usage in China and have well-defined monograph in the Chinese Pharmacopeia. These indicate their relatively high clinical safety and may have a quicker drug development process than that of a new novel antibiotic. Based on the results of this study, the authors will perform further in vitro and animal studies, aiming to accumulate significant data for the application of clinical trial. AbstractAntibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillinresistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 constituents of the four herbs to the two common MRSA inhibitory targets, penicillin binding proteins 2a (PBP2a) and 4 (PBP4). The physicochemical and absorption, distribution, metabolism, and excretion properties and drug safety profiles of these compounds were also analyzed. D. genkwa extract potentiated the antibacterial effects of oxacillin against MRSA, as indicated by an FIC index value of 0.375. M. officinalis and V. officinalis produced partial synergistic effects when combined with oxacillin, whereas M. charantia was found to have no beneficial effects in inhibiting MRSA. Overall, tiliroside, pinoresinol, magnatriol B, and momorcharaside B were predicted to be PBP2a or PBP4 inhibitors with good drug-like properties. This study identifies compounds that deserve further investigation with the aim of developing therapeutic agents to modulate the effect of antibiotics on MRSA.

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Section: Pbp4mentioning

confidence: 99%

Section: 29mentioning

confidence: 99%

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study

Kuok

Hoi

et al. 2017

Exp Biol Med (Maywood)

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“…Recently, single-nucleotide polymorphisms (SNPs) in the penicillin-binding protein 4 (pbp4) gene have been discovered to play a role in ␤-lactam and vancomycin resistance as well as disease progression in S. aureus (45)(46)(47). Gygax et al (48) observed similar effects on pbp4 in relation to penicillin tolerance in group B streptococci.…”

mentioning

confidence: 52%

Detection of Epidemic USA300 Community-Associated Methicillin-Resistant Staphylococcus aureus Strains by Use of a Single Allele-Specific PCR Assay Targeting a Novel Polymorphism of Staphylococcus aureus pbp3

et al. 2013

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In recent years, the dramatic increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections has become a significant health care challenge. Early detection of CA-MRSA is important because of its increased virulence associated with the arginine catabolic mobile element (ACME), Panton-Valentine leukocidin (PVL), and other toxins that may contribute to disease severity. In particular, the USA300 epidemic clone has emerged and now represents the cause of as much as 98% of CA-MRSA skin and soft tissue infections in the United States. Current diagnostic assays used to identify CA-MRSA strains are based on complex multiplex PCRs targeting the staphylococcal cassette chromosome mec (SCCmec) DNA junction, a multitude of genes, and noncoding DNA fragments or on a number of lengthy sequencetyping methods. Here, two nucleotide polymorphisms, G88A and G2047A, that were found to be in strict linkage disequilibrium in the S. aureus penicillin-binding protein 3 (pbp3) gene were also found to be highly associated with the USA300 clone of CA-MRSA. Clinical isolates that contained this pbp3 allele were also positive for the presence of SCCmec type IV, the ACME, and the PVL toxin gene and matched the t008 or t121 molecular spa types, which are associated specifically with the USA300 CA-MRSA clone. A single allele-specific PCR targeting the G88A polymorphism was developed and was found to be 100% sensitive and specific for the detection of USA300 CA-MRSA and 91.5% sensitive and 100% specific for the detection of all CA-MRSA isolates in this study.

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“…The PBP2 is a bifunctional protein produced by S. aureus and has binding speciicity to β-lactam antibiotics. This protein presented a functional transpeptidase domain and carboxypeptidase domain; it is directly linked to the cell wall metabolism in bacteria [53]. In S. aureus, both PBPs and (PBP2) are membrane-associated proteins that catalyze the inal step of peptidoglycan biosynthesis.…”

Section: Mechanisms Resistant To β-Lactam Antibiotics Associated To Pmentioning

confidence: 99%

“…In S. aureus, both PBPs and (PBP2) are membrane-associated proteins that catalyze the inal step of peptidoglycan biosynthesis. The transpeptidase and carboxypeptidase activities of PBPs occur at the D-Ala-D-Ala terminus of a peptidoglycan precursor containing N-acetylglucosamine and N-acetyl-muramic acid L-Ala-D-Glu-L-Lys-D-Ala-D-Ala (pentapeptide chain) [53].…”

Section: Mechanisms Resistant To β-Lactam Antibiotics Associated To Pmentioning

confidence: 99%

Effects of Alterations in Staphylococcus aureus Cell Membrane and Cell Wall in Antimicrobial Resistance

Monteiro¹,

Neto²,

Mendes³

et al. 2017

The Rise of Virulence and Antibiotic Resistance in ≪i>Staphylococcus Aureus

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Staphylococcus aureus is one of the most successful opportunistic pathogen able to cause serious infections due to its ability to produce virulence factors and acquire antimicrobial resistance. Recent reports indicate that the phenotypic changes in the cell wall and cell membrane are essential mechanisms related to the resistance to several antibacterial drugs (such as daptomycin and vancomycin). These alterations involve changes in cell wall composition and chemical modiications of some components (point mutation leading to modiication in phosphatidylglycerol molecule, in the production of the aberrations in peptidoglycan structure and decrease in autolytic activity of the components of the cell envelope), leading to changes in electric charge of the cell surface, cell membrane luidity and cell morphology. In fact, S. aureus develops several multifactorial and strainspeciic adaptive mechanisms to survival in host. The study of such mechanisms is very important. The aim of this chapter is to review the phenotypic mechanisms related to drug resistance in S. aureus.

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Molecular Basis for the Role of Staphylococcus aureus Penicillin Binding Protein 4 in Antimicrobial Resistance

Cited by 81 publications

References 46 publications

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study

Detection of Epidemic USA300 Community-Associated Methicillin-Resistant Staphylococcus aureus Strains by Use of a Single Allele-Specific PCR Assay Targeting a Novel Polymorphism of Staphylococcus aureus pbp3

Effects of Alterations in Staphylococcus aureus Cell Membrane and Cell Wall in Antimicrobial Resistance

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