Dataset Information

Transcriptional Analysis of the Effects of Gambogic Acid and Neogambogic Acid on Methicillin-Resistant Staphylococcus aureus.

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major threat to human health, as this bacterium has developed resistance to a variety of conventional antibiotics. This is especially true of MRSA biofilms, which not only exhibit enhanced pathogenicity but also are resistant to most antibiotics. In this work, we demonstrated that two natural products with antitumor activity, namely, gambogic acid (GA) and neogambogic acid (NGA), have significant inhibitory activity toward MRSA. GA and NGA can not only effectively inhibit planktonic MRSA strains in vivo and in vitro, but also have strong inhibitory effects on MRSA biofilms formation. By transcriptome sequencing, Q-RT-PCR and PRM, we found that GA and NGA could reduce the expression of S. aureus virulence factors by inhibiting the saeRS two-component, thus achieving inhibition of MRSA. We found that GA and NGA had anti-MRSA activity in vivo and in vitro and identified saeRS to be the target, indicating that saeRS inhibitors may be used to treat biofilm-related infections.

SUBMITTER: Hua X

PROVIDER: S-EPMC6753875 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Transcriptional Analysis of the Effects of Gambogic Acid and Neogambogic Acid on Methicillin-Resistant <i>Staphylococcus aureus</i>.

Hua Xin X Jia Yue Y Yang Qin Q Zhang Wanjiang W Dong Zhimin Z Liu Siguo S

Frontiers in pharmacology 20190913

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infection is a major threat to human health, as this bacterium has developed resistance to a variety of conventional antibiotics. This is especially true of MRSA biofilms, which not only exhibit enhanced pathogenicity but also are resistant to most antibiotics. In this work, we demonstrated that two natural products with antitumor activity, namely, gambogic acid (GA) and neogambogic acid (NGA), have significant inhibitory activity toward ...[more]

PMID: 31572177

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Project description:Methicillin resistant Staphylococcus aureus (MRSA) infection is becoming refractory to existing antibiotic therapy owing to the inherent ability of S. aureus to develop rapid resistance and is considered a major threat to public health. We found that a natural isolate of Bacillus pumilus from the Columbia River Estuary produces a strong anti-MRSA compound, amicoumacin A. As amicoumacin A has been reported to exhibit anti-microbial, anti-inflammatory, and anti-ulcer activities, we sought to uncover its mechanism of action. Genome-wide transcriptome analysis of S. aureus COL in response to amicoumacin A showed alteration in the expression of genes involved in several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which has been shown to be induced in response to a collapse of membrane potential. In order to gain further insight into the mechanism of action of amicoumacin A, a whole genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated by serial passage method was carried out. Single point mutations resulting in codon substitutions were uncovered in several distinct genes: ksgA, RNA dimethyltranferase; fusA, elongation factor G; dnaG, primase, ; lacD, tagatose 1,6-bisphosphate aldolase, ; and SACOL0611, encoding a putative glycosyl transferase gene. Based on these results, a candidate approach was undertaken to recreate the same amino acid substitution individually in FusA and KsgA, each of which resulted in two-fold resistance towards amicoumacin A. The fusA gene is known as the site for fusidic acid- resistant mutations; however the codon substitutions in EF-G that cause amicoumacin A resistance and fusidic acid resistance occur in separate domains and do not bring about cross resistance. Taken together, these results suggest that amicoumacin A might cause perturbation of the cell membrane and lead to energy dissipation. Decreased rates of cellular metabolism including protein synthesis and DNA replication in resistant strains might allow cells to compensate for membrane dysfunction and thus increase cell survivability.

Dataset Information

Transcriptional Analysis of the Effects of Gambogic Acid and Neogambogic Acid on Methicillin-Resistant Staphylococcus aureus.

Publications

Transcriptional Analysis of the Effects of Gambogic Acid and Neogambogic Acid on Methicillin-Resistant <i>Staphylococcus aureus</i>.

Similar Datasets

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