Relationship between morphological changes and endotoxin release induced by carbapenems in Pseudomonas aeruginosa

Horii, Toshinobu; Ichiyama, Satoshi; Ohta, Michio; Kobayashi, Miya

doi:10.1099/00222615-48-3-309

Cited by 28 publications

(28 citation statements)

References 18 publications

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“…Additionally, the level of antibiotics-induced endotoxin release from round-shaped bacteria is also shown to be lower than that from filamentous-shaped bacteria. 14,15) Thus, induction of a round-shape is favorable in antibacterial therapy.…”

Section: Discussionmentioning

confidence: 99%

Anti-Pseudomonas aeruginosa Compound, 1,2,3,4-Tetrahydro-1,3,5-triazine Derivative, Exerts Its Action by Primarily Targeting MreB

Yamachika

Sugihara

Tsuji

et al. 2012

Biological & Pharmaceutical Bulletin

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In order to find new anti-Pseudomonas agents, we carried out whole-cell based P. aeruginosa growth assay, and identified 1,2,3,4-tetrahydro-1,3,5-triazine (Compound A). This compound showed anti-Pseudomonas activity against wild as well as pumpless strain equally at a same concentration. Also, this compound was structurally very similar to A22, which is known to inhibit the bacterial actin-like protein MreB. By the analysis of resistant strains, the primary target of this compound in P. aeruginosa was definitely confirmed to be MreB. In addition, these compounds showed a bacteriostatic effect, and induced the morphology changes in P. aeruginosa from rod shape to sphere shape, which leads to be clinically favorable in terms of susceptibility to phagocytosis and release of endotoxin. These results display that Compound A is a very attractive compound which shows anti-P. aeruginosa activity based on inhibition of MreB without being affected by efflux pumps, and could provide a new step toward development of new promising anti-Pseudomonas agents, MreB inhibitors.

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Section: Discussionmentioning

confidence: 99%

Anti-Pseudomonas aeruginosa Compound, 1,2,3,4-Tetrahydro-1,3,5-triazine Derivative, Exerts Its Action by Primarily Targeting MreB

Yamachika

Sugihara

Tsuji

et al. 2012

Biological & Pharmaceutical Bulletin

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“…Our previous reports [11,21] showed a correlation between ET release and morphological changes in cells of P. aeruginosa . Although recent reports have thoroughly characterized the time course and magnitude of carbapenem-induced ET release in P. aeruginosa [11] , little is known concerning the carbapenem-induced release of ETA and PG.…”

mentioning

confidence: 99%

“…A number of previous studies [11,[19][20][21][22][23] , however, have demonstrated that exposure of Gram-negative bacteria to antibiotics can increase the amount of ET released both in vitro and in vivo, and can worsen Gram-negative infections [24,25] . Our previous reports [11,21] showed a correlation between ET release and morphological changes in cells of P. aeruginosa . Although recent reports have thoroughly characterized the time course and magnitude of carbapenem-induced ET release in P. aeruginosa [11] , little is known concerning the carbapenem-induced release of ETA and PG.…”

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confidence: 99%

Release of Exotoxin A, Peptidoglycan and Endotoxin after Exposure of Clinical Pseudomonas aeruginosa Isolates to Carbapenems in vitro

Horii

Muramatsu²,

Monji³

et al. 2005

Chemotherapy

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Background: Production of several cell-associated components and extracellular enzymes can play important roles in the pathogenesis of Pseudomonas aeruginosa infections. Methods: We characterized the time course of morphological changes, production of exotoxin A (ETA) and release of peptidoglycan (PG) and endotoxin (ET) in clinical P. aeruginosa isolates after exposure to carbapenems including imipenem, panipenem, meropenem and biapenem at 0.5, 2, 8 and 32 µg/ml. Results: The amount of ETA in the supernatant of bacterial cultures exposed to carbapenems correlated with the number of viable cells, independently of morphological changes. Formation of ovoid cells and rapid cell lysis induced by carbapenems above the minimal inhibitory concentrations (MICs) decreased ETA production and ET release, while filamentation and prolonged cell lysis increased ETA production and/or ET release. Neither the number of viable cells nor bacterial morphology was related to the amount of PG released throughout the 6-hour observation period. Conclusion: Exposure to concentrations of carbapenems above the MIC resulted in rapid cell lysis of P. aeruginosa and decreased ETA levels and ET release, while filamentation and prolonged cell lysis induced by exposure to sub-MICs of carbapenems were associated with increased ETA production and/or greater ET release.

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“…Our observations by CLSM (Fig. 5) did not reveal any modification of cell morphology, while the cell damage cause by ceftazidime treatment is considered characteristic of the damage induced by beta-lactam molecules, which consisted of the elongation of specific cells (52), and molecules such as tobramycin induced abnormal proteins that were even incorporated into the cell wall, resulting in an apparent loss of integrity or elasticity and a rough appearance, as demonstrated by atomic force microscopy observations (53). So, under our conditions, the inhibition of C 4 -HSL did not allow ceftazidime to reach its cellular target (periplasmic transpeptidases and carboxypeptidases) and/or to induce significant effects, given that peptidoglycan synthesis is involved in the cell division process.…”

Section: Discussionmentioning

confidence: 89%

Impairment of Pseudomonas aeruginosa Biofilm Resistance to Antibiotics by Combining the Drugs with a New Quorum-Sensing Inhibitor

Furiga

Lajoie

Hage

et al. 2016

Antimicrob Agents Chemother

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Pseudomonas aeruginosa plays an important role in chronic lung infections among patients with cystic fibrosis (CF) through its ability to form antibiotic-resistant biofilms. In P. aeruginosa, biofilm development and the production of several virulence factors are mainly regulated by the rhl and las quorum-sensing (QS) systems, which are controlled by two N-acyl-homoserine lactone signal molecules. In a previous study, we discovered an original QS inhibitor, N-(2-pyrimidyl)butanamide, called C11, based on the structure of C 4 -homoserine lactone, and found that it is able to significantly inhibit P. aeruginosa biofilm formation. However, recent data indicate that P. aeruginosa grows under anaerobic conditions and forms biofilms in the lungs of CF patients that are denser and more robust than those formed under aerobic conditions. Our confocal microscopy observations of P. aeruginosa biofilms developed under aerobic and anaerobic conditions confirmed that the biofilms formed under these two conditions have radically different architectures. C11 showed significant dose-dependent antibiofilm activity on biofilms grown under both aerobic and anaerobic conditions, with a greater inhibitory effect being seen under conditions of anaerobiosis. Gene expression analyses performed by quantitative reverse transcriptase PCR showed that C11 led to the significant downregulation of rhl QS regulatory genes but also to the downregulation of both las QS regulatory genes and QS system-regulated virulence genes, rhlA and lasB. Furthermore, the activity of C11 in combination with antibiotics against P. aeruginosa biofilms was tested, and synergistic antibiofilm activity between C11 and ciprofloxacin, tobramycin, and colistin was obtained under both aerobic and anaerobic conditions. This study demonstrates that C11 may increase the efficacy of treatments for P. aeruginosa infections by increasing the susceptibility of biofilms to antibiotics and by attenuating the pathogenicity of the bacterium.

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Relationship between morphological changes and endotoxin release induced by carbapenems in Pseudomonas aeruginosa

Cited by 28 publications

References 18 publications

Anti-<i>Pseudomonas aeruginosa</i> Compound, 1,2,3,4-Tetrahydro-1,3,5-triazine Derivative, Exerts Its Action by Primarily Targeting MreB

Anti-<i>Pseudomonas aeruginosa</i> Compound, 1,2,3,4-Tetrahydro-1,3,5-triazine Derivative, Exerts Its Action by Primarily Targeting MreB

Release of Exotoxin A, Peptidoglycan and Endotoxin after Exposure of Clinical <i>Pseudomonas aeruginosa</i> Isolates to Carbapenems in vitro

Impairment of Pseudomonas aeruginosa Biofilm Resistance to Antibiotics by Combining the Drugs with a New Quorum-Sensing Inhibitor

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