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Related Concept Videos

Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Determinants of Bacterial Pathogenicity and Virulence01:20

Determinants of Bacterial Pathogenicity and Virulence

Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...
Staphylococcal Skin Infections01:29

Staphylococcal Skin Infections

Staphylococcus aureus is a Gram-positive coccus that resides harmlessly on the skin and mucous membranes of healthy individuals. When the skin barrier is breached, it can shift from a commensal to an opportunistic pathogen. This transition is facilitated by surface adhesins, such as clumping factor B and S. aureus surface protein G (SasG), which bind to structural proteins, including loricrin and cytokeratin, in the damaged epidermis. Protein A, another key factor, binds the Fc region of...
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...

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Related Experiment Video

Updated: May 29, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
07:51

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method

Published on: May 21, 2018

Host-Pathogen Dual Targeting With Repurposed Drugs Identifies a Synergistic Therapy for Intracellular Staphylococcus

Blanca Lorente-Torres1, Helena Á Ferrero1, Pablo Castañera1

  • 1Departamento de Biología Molecular, Área de Microbiología, Universidad de León, León, Spain.

Microbiologyopen
|May 28, 2026
PubMed
Summary
This summary is machine-generated.

Researchers screened approved drugs to find new ways to fight Staphylococcus aureus infections inside host cells. They discovered 5-fluoro-2'-deoxycytidine (5-FdC) combined with rifapentine (5FR) effectively clears bacteria by activating host defenses.

Keywords:
Staphylococcus aureusantimicrobial resistancecombination therapydrug repurposingintracellular infectionlarvaemice

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High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
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Last Updated: May 29, 2026

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High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
09:09

High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity

Published on: November 16, 2016

Area of Science:

  • Infectious Diseases
  • Drug Discovery
  • Host-Pathogen Interactions

Background:

  • Staphylococcus aureus causes severe infections like pneumonia and sepsis.
  • Intracellular survival of S. aureus limits antibiotic efficacy.
  • Drug repurposing is a strategy to find new antibacterial agents.

Purpose of the Study:

  • To identify clinically approved compounds that enhance intracellular S. aureus killing.
  • To evaluate the synergistic potential of identified compounds with rifapentine.
  • To elucidate the host-pathway modulation mechanisms underlying the observed antibacterial effects.

Main Methods:

  • High-throughput screening of 6297 approved compounds in S. aureus-infected A549 cells.
  • Synergy testing of lead compounds with rifapentine against MRSA and MSSA.
  • Metabolomic and RNA-sequencing analyses to assess host response.
  • In vivo efficacy testing in Galleria mellonella and murine pneumonia models.

Main Results:

  • 5-fluoro-2 -deoxycytidine (5-FdC) was identified as an effective intracellular inhibitor.
  • The combination of 5-FdC and rifapentine (5FR) showed synergistic activity against diverse S. aureus strains and host cells.
  • 5-FdC activated host stress and DNA damage response (DDR) pathways, restoring metabolic balance.
  • The 5FR combination reduced bacterial loads in vivo without toxicity.

Conclusions:

  • This study presents the largest drug repurposing screen against intracellular S. aureus.
  • A synergistic combination of 5-FdC and rifapentine enhances bacterial clearance.
  • The combination targets both host and pathogen by modulating host DDR, stress, and metabolic responses.