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Related Concept Videos

Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

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Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
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Cellular Membranes and Drug Transport01:24

Cellular Membranes and Drug Transport

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Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
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Pore Transport and Ion-Pair Transport01:17

Pore Transport and Ion-Pair Transport

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Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited  but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
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Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport01:23

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Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
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Carrier-Mediated Transport01:06

Carrier-Mediated Transport

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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
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Surface Membrane Barriers01:18

Surface Membrane Barriers

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The skin and mucous membranes serve as the primary line of defense against pathogens by providing both physical and chemical protection. These barriers are essential in preventing the entry and establishment of microbes, thereby maintaining the integrity of the host.
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
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Related Experiment Video

Updated: Sep 19, 2025

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
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The Mycomembrane Differentially and Heterogeneously Restricts Antibiotic Permeation.

Irene Lepori1, Kiserian Jackson1,2, Zichen Liu3,4

  • 1Department of Microbiology, University of Massachusetts, Amherst, Massachusetts 01003, United States.

ACS Infectious Diseases
|June 5, 2025
PubMed
Summary
This summary is machine-generated.

The mycobacterial outer membrane selectively blocks antibiotic entry, acting as a cell-specific barrier. This finding, using the Peptidoglycan Accessibility Click-Mediated AssessmeNt (PAC-MAN) method, reveals differential drug permeation in Mycobacterium tuberculosis.

Keywords:
antibioticsbioorthogonal click chemistrycell envelopepermeabilitytuberculosis

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Area of Science:

  • Microbiology
  • Cell Biology
  • Drug Discovery

Background:

  • The outer mycomembrane of Mycobacterium tuberculosis is widely considered a primary barrier to antibiotic treatment.
  • Previous studies supporting this hypothesis relied on indirect evidence or bulk population measurements.

Purpose of the Study:

  • To investigate the role of the mycobacterial mycomembrane as a barrier to antibiotic entry using a novel method.
  • To determine if the mycomembrane exhibits differential permeability to various molecules and antibiotics.

Main Methods:

  • Utilized the Peptidoglycan Accessibility Click-Mediated AssessmeNt (PAC-MAN) method to trap azide-modified small molecules within the peptidoglycan layer of live mycobacteria.
  • Applied PAC-MAN to analyze the differential restriction of fluorophores and antibiotic derivatives by the mycomembrane.

Main Results:

  • The mycomembrane was shown to differentially restrict access of fluorophores and antibiotic derivatives in both M. tuberculosis and M. smegmatis.
  • Discrimination was observed between different classes of antibiotics and within the fluoroquinolone family.
  • Analysis of subpopulations revealed heterogeneous restriction of certain fluorophores and vancomycin by the mycomembrane.

Conclusions:

  • The mycobacterial mycomembrane acts as a dynamic, molecule- and cell-specific barrier to antibiotic permeation.
  • This finding has significant implications for understanding antibiotic resistance and developing new therapeutic strategies against tuberculosis.