Introduction to Clinical Microbiology
Keith Struthers in Clinical Microbiology, 2017
The cell wall of gram-negative bacteria is more complex than that of gram-positive bacteria (Figure 1.6). The outer lipid bilayer has proteins, such as adhesins, and flagella traversing it. Porins act as channels that allow hydrated molecules to pass through the membrane. From the periplasmic space, molecules can be transported across the cytoplasmic membrane into the cell. It should be noted that porins enable antibiotics such as the β-lactams to reach their site of action. Benzylpenicillin is not effective against most gram-negative organisms because it is not sufficiently polar to pass through a porin channel. Ampicillin, a derivative of benzylpenicillin, differs in the addition of an amino group on the side chain (Figure 1.10). The polar ampicillin passes through the hydrated porin channel into the periplasmic space where it can act on the PBP.
Acinetobacter Species: Resistance Update and Treatment Options
Robert C. Owens, Lautenbach Ebbing in Antimicrobial Resistance, 2007
The second category of resistance mechanisms reduces the ability of antimicrobial agents to reach their intended bacterial target(s). Porin channels and other outer membrane proteins in the bacterial cell membrane are important for transport of antimicrobial agents into the cell to gain access to bacterial targets. Carbapenem resistance in Acinetobacter has been linked to the loss of proteins from the outer membrane of the bacterium and these proteins are thought to be porin channels (48,54,55). It is likely that beta-lactamases and outer membrane alterations such as modified porin channels work together to confer resistance to beta-lactam agents (46). Efflux pumps also work to reduce the ability of antimicrobial agents to reach their intended bacterial target by removing or expelling the agents. Similar to Pseudomonas, Acinetobacter possesses efflux pumps that are capable of actively removing a broad range of antimicrobial agents from the bacterial cell (46).
Structure, Function and Evolutionary Aspects of Mitochondria
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
The membranes of mitochondria divide the organelle in two aqueous parts; one is the matrix which is present inside the inner membrane and another is intermembrane space which is present between the outer and inner membrane of mitochondria. The matrix is like a gel due to the presence of thousands of water soluble proteins inside the structure. Half of the outer membrane of mitochondria is composed of lipids by weight and also a mixture of enzyme that have different type of activities. The outer membrane contains porins having large internal channels. These porin channels are permeable to the molecules like Co-A, NAD, ATP when the channels are in wide open configuration. The inner mitochondrial membrane contains 100 non-identical polypeptides and a protein/lipid ratio of 3:1. The inner membrane contains cardiolipin, a phospholipid which have similar characteristics like bacterial plasma membrane. The inner membrane is impermeable to most of the molecules. To enter through inner membrane the molecules need to have a special type of membrane transporter.
Multidrug-resistant Klebsiella pneumoniae: mechanisms of resistance including updated data for novel β-lactam-β-lactamase inhibitor combinations
Published in Expert Review of Anti-infective Therapy, 2021
Irene Galani, Ilias Karaiskos, Helen Giamarellou
Porins are transmembrane β-barrel proteins that exist as trimers, creating channels of defined size and are found in the outer membrane of Gram-negative bacteria. Porins regulate the nonspecific diffusion of hydrophilic solutes and other small molecules through the outer membrane. Enterobacterales commonly express two major nonspecific porins with similar functions, differing in their permeability to small molecules. These nonspecific porins play an important role in nutrient acquisition but also mediate the passive diffusion of antibiotics across the outer membrane and are closely associated with antibiotic resistance in the Gram-negative bacteria [75,76]. Decreased outer membrane porin expression in antibiotic resistant isolates has been correlated with an increased minimum inhibitory concentration (MIC) to multiple antibiotics, most commonly those that target peptidoglycan synthesis [77–79].
Overcoming problems of poor drug penetration into bacteria: challenges and strategies for medicinal chemists
Published in Expert Opinion on Drug Discovery, 2018
Davide Benedetto Tiz, Danijel Kikelj, Nace Zidar
One possible reason for the dissimilar properties of anti-Gram-positive and anti-Gram-negative drugs is the abundant occurrence of porins in the OM of Gram-negative bacteria. Porins are hydrophilic channels, which serve as a major entry point for hydrophilic compounds. They have to displace a hydration sphere within a channel in order to pass through the pore. Lipophilic compounds are not able to displace the water molecules from the pore, which makes their crossing of the outer shell of Gram-negative bacteria less thermodynamically favorable. On the other hand, small hydrophilic molecules, which can bypass the OM, are very likely to be hindered by the cellular membrane, which favors neutral, lipophilic compounds [58]. Gram-negative organisms have, by evolution, acquired selective pathways for the entry of essential nutrients, and developed outer and cytoplasmic membranes endowed with orthogonal sieving properties that make permeation of non-necessary compounds very difficult [58].
How to discover new antibiotic resistance genes?
Published in Expert Review of Molecular Diagnostics, 2019
Linda Hadjadj, Sophie Alexandra Baron, Seydina M. Diene, Jean-Marc Rolain
AR related to reduction of membrane permeability consists in limiting antibiotic entry into the bacterial cell due to cell surface changes. This change limits drug interactions, as is the case with lipid A modifications, or reduce the number of entry channels, such as porins located in the outer membrane. Main function of porins is to create a selective channel for the diffusion of hydrophilic molecules. Alteration of genes encoding porins leads to resistance by membrane impermeability as is the case for the oprD gene in Pseudomonas aeruginosa, whose alteration makes the strain insensitive to carbapenems [28]. Mutagenesis and transposon mutagenesis methods can be used to prove the role of these genes in AR mechanisms [29]. Bacteria have the ability to increase their resistance by actively expelling the antibiotic from the cells using efflux pumps to prevent the intracellular accumulation of toxic compounds. Efflux pumps can be transferable via plasmids, but most multiresistance systems are chromosomally encoded. The same efflux system may be involved in resistance to different classes of antibiotics as in the case of MdfA in E. coli which has an action on aminoglycosides, chloramphenicol, erythromycin, fluoroquinolones, rifampin, and tetracycline [28]. Transposon mutagenesis has made it possible to highlight the role of certain efflux pumps in AR mechanisms [30].AR mechanisms due to membrane permeability or efflux pumps activity are various and can be cumulative (Figure 1, Table 2).
Related Knowledge Centers
- Bacterial Outer Membrane
- Beta Barrel
- Diffusion
- Molecule
- Protein
- Cell Membrane
- Ion Channel
- Passive Transport
- Membrane Transport Protein
- Gram-Negative Bacteria