The effect of lipopolysaccharide on lipid bilayer permeability of β‐lactam antibiotics

Hiruma, Ryoichi; Yamaguchi, Akihito; Sawai, Tetsuo

doi:10.1016/0014-5793(84)81326-5

Cited by 26 publications

(15 citation statements)

References 21 publications

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“…Several hypotheses can explain how LPS modulates Gram-negative outer envelope permeability. Nikaido and coworkers have suggested that the carbohydrate moiety would act as a barrier against hydrophobic molecules (25), thus explaining why the permeativity of some antibiotics (e.g., cephalosporins) is proportional to their hydrophobicity (19). In fact, X-ray diffraction studies suggest that LPS thickness (i.e., its polysaccharide content) is inversely proportional to outer membrane permeability (29), supporting the aforementioned hypothesis (25).…”

Section: Discussionmentioning

confidence: 87%

Antimicrobial Action and Cell Agglutination by the Eosinophil Cationic Protein Are Modulated by the Cell Wall Lipopolysaccharide Structure

Pulido

Moussaoui

Andreu

et al. 2012

Antimicrob Agents Chemother

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Antimicrobial proteins and peptides (AMPs) are essential effectors of innate immunity, acting as a first line of defense against bacterial infections. Many AMPs exhibit high affinity for cell wall structures such as lipopolysaccharide (LPS), a potent endotoxin able to induce sepsis. Hence, understanding how AMPs can interact with and neutralize LPS endotoxin is of special relevance for human health. Eosinophil cationic protein (ECP) is an eosinophil secreted protein with high activity against both Gram-negative and Gram-positive bacteria. ECP has a remarkable affinity for LPS and a distinctive agglutinating activity. By using a battery of LPS-truncated E. coli mutant strains, we demonstrate that the polysaccharide moiety of LPS is essential for ECP-mediated bacterial agglutination, thereby modulating its antimicrobial action. The mechanism of action of ECP at the bacterial surface is drastically affected by the LPS structure and in particular by its polysaccharide moiety. We have also analyzed an N-terminal fragment that retains the whole protein activity and displays similar cell agglutination behavior. Conversely, a fragment with further minimization of the antimicrobial domain, though retaining the antimicrobial capacity, significantly loses its agglutinating activity, exhibiting a different mechanism of action which is not dependent on the LPS composition. The results highlight the correlation between the protein's antimicrobial activity and its ability to interact with the LPS outer layer and promote bacterial agglutination.

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Section: Discussionmentioning

confidence: 87%

Antimicrobial Action and Cell Agglutination by the Eosinophil Cationic Protein Are Modulated by the Cell Wall Lipopolysaccharide Structure

Pulido

Moussaoui

Andreu

et al. 2012

Antimicrob Agents Chemother

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“…The occurrence of negatively charged phosphate groups, decorating most LPS macromolecules, contributes to the structure and the low fluidity of the LPS monolayer, because they engage in electrostatic interactions with divalent cations such as calcium (Ca 2+ ) and magnesium (Mg 2+ ) normally present on the surface of the OM . This is reflected in bacterial resistance to harsh conditions, as in the case of extremophiles, as well as in the case of bacteria exposed to dangerous external compounds, such as antibiotics . A plethora of other features characterizing the LPS structure have been demonstrated to be involved in the capability of the bacteria to resist stress factors .…”

Section: Lpss From Gram‐negative Mesophilic Bacteria: Overviewmentioning

confidence: 99%

“…[12][13][14][15] This is reflected in bacterial resistance to harsh conditions, as in the case of extremophiles, as well as in the case of bacteria exposed to dangerous external compounds, such as antibiotics. [29] A plethora of other features characterizing the LPS structure have been demonstrated to be involved in the capability of the bacteria to resist stress factors. [12][13][14][15] Given the wide structural heterogeneity of LPS structures, it is reasonable to assume that the external environment is one of the key drivers in promoting such high structural diversity.…”

Section: Lpss From Gram-negative Mesophilic Bacteria: Overviewmentioning

confidence: 99%

Gram‐Negative Extremophile Lipopolysaccharides: Promising Source of Inspiration for a New Generation of Endotoxin Antagonists

et al. 2017

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Extremophiles are microorganisms exhibiting the fascinating capability to thrive in habitats that are considered clearly inhospitable. Extreme-loving microorganisms have acquired ever-increasing importance in the biomedical and pharmaceutical fields, with many of their bioactive products having long been used as life-saving drugs. In this context, extremophile Gram-negative bacterial lipopolysaccharides (LPSs) and their analogues offer many promising opportunities for a variety of biomedical and therapeutic applications. The structure-dependent capability to elicit and to modulate host immune responses is surely the most intriguing feature of LPSs in the context of new drug discovery and design. This review offers an overview of the chemical peculiarities of LPSs isolated from extremophile bacteria, providing the most promising results relating to their biological activity. We discuss the pharmacologically important potential of extremophile LPSs as fundamental immunomodulatory compounds from the perspective of drug synthesis and development

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“…The contribution of LPS to the barrier effect has been demonstrated with E. coli [38], but not with Bacteroides spp. [39].…”

Section: Reduced Antibiotic Penetrationmentioning

confidence: 99%

Resistance to -Lactam Antibiotics in Bacteroides Spp.

Edwards¹

1997

Journal of Medical Microbiology

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Bacteroides spp., particularly B. fragilis, are well-recognised bacterial pathogens. Production of the typical P-lactamases of Bacteroides restricts the therapeutic use of P-lactam agents mainly to the P-lactamase inhibitor combinations and carbapenems. These compounds have the advantage of broad-spectrum activity and the ability to combat polymicrobial infections. Resistance of Bacteroides spp. to P-lactam antibiotics appears to be increasing, largely because of an overall increase in P-lactamase activity. There has been a rise in the prevalence of isolates showing high-level production of typical Bacteroides P-lactamases and an increase in reports other potent p-lactamase types. In the case of B. fragilis, metallo-enzymes are a particular threat to current therapeutic practice, as they are not inhibited by common P-lactamase inhibitors and are able to hydrolyse carbapenems. The presence of permeability barriers may confer low-level p-lactam resistance and supplement the effect of P-lactamase activity. There are also sporadic reports of loss of /?-lactam activity because of reduced affinity of the penicillin-binding proteins.

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The effect of lipopolysaccharide on lipid bilayer permeability of β‐lactam antibiotics

Cited by 26 publications

References 21 publications

Antimicrobial Action and Cell Agglutination by the Eosinophil Cationic Protein Are Modulated by the Cell Wall Lipopolysaccharide Structure

Antimicrobial Action and Cell Agglutination by the Eosinophil Cationic Protein Are Modulated by the Cell Wall Lipopolysaccharide Structure

Gram‐Negative Extremophile Lipopolysaccharides: Promising Source of Inspiration for a New Generation of Endotoxin Antagonists

Resistance to -Lactam Antibiotics in Bacteroides Spp.

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