Cell wall and membrane changes associated with ethambutol resistance in Mycobacterium tuberculosis H37Ra

Sareen, M. L.; Khuller, G. K.

doi:10.1128/aac.34.9.1773

Cited by 26 publications

(11 citation statements)

References 21 publications

(13 reference statements)

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“…The decrease in phosphorus may reflect a lower content of phospholipids and a higher content of glyco-or aminolipids. Reduction in the content of phospholipids has also been observed in the following: antibiotics in Pseudomonas aeruginosa (Conrad and Galano 1989); bacteriocins in L. monocytogenes (Ming and Daeschel 1995); ethanbutol in Mycobacterium tuberculosis (Sareen and Khuller 1990); benzoic acid in L. monocytogenes in our previous study (Mastronicolis et al 2010). The NL percentage also remained invariable in L. monocytogenes in the presence of benzoic acid (Mastronicolis et al 2010).…”

Section: Discussionsupporting

confidence: 62%

Adaptational changes in cellular phospholipids and fatty acid composition of the food pathogen Listeria monocytogenes as a stress response to disinfectant sanitizer benzalkonium chloride

Bisbiroulas

Psylou

Iliopoulou

et al. 2011

Letters in Applied Microbiology

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Aims: This study provides a first approach to observing the alterations of the cell membrane lipids in the adaptation response of Listeria monocytogenes to the sanitizer benzalkonium chloride. Methods and Results: A thorough investigation of the composition of polar and neutral lipids from L. monocytogenes grown when exposed to benzalkonium chloride is compared to cells optimally grown. The adaptation mechanism of L. monocytogenes in the presence of benzalkonium chloride caused (i) an increase in saturated‐chain fatty acids (mainly C16:0 and C18:0) and unsaturated fatty acids (mainly C16:1 and C18:1) at the expense of branched‐chain fatty acids (mainly Ca‐15:0 and Ca‐17:0) mainly because of neutral fatty acids; (ii) no alteration in the percentage of neutral and polar lipid content among total lipids; (iii) a decrease in lipid phosphorus and (iv) an obvious increase in the anionic phospholipids and a decrease in the amphiphilic phosphoaminolipid. Conclusions: These lipid changes could lead to decreased membrane fluidity and also to modifications of physicochemical properties of cell surface and thus changes in bacterial adhesion to abiotic surfaces. Significance and Impact of the Study: The adaptation and resistance of L. monocytogenes to disinfectants is able to change its physiology to allow growth in food‐processing plants. Understanding microbial stress response mechanisms would improve the effective use of disinfectants.

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Section: Discussionsupporting

confidence: 62%

Adaptational changes in cellular phospholipids and fatty acid composition of the food pathogen Listeria monocytogenes as a stress response to disinfectant sanitizer benzalkonium chloride

Bisbiroulas

Psylou

Iliopoulou

et al. 2011

Letters in Applied Microbiology

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“…If clarithromycin affects cell wall and membrane architecture in M. tuberculosis as it apparently does in M. avium complex (26), it is conceivable that this disruption allows isoniazid, rifampin, and/or ethambutol to gain access to the drug-resistant cell. This assumes that impermeability plays an important role in resistance to these drugs, a view held by some investigators (20,28). The fact that the strains in this study are resistant to clarithromycin argues against this hypothesis.…”

Section: Discussioncontrasting

confidence: 46%

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

Cavalieri

Biehle

Sanders

1995

Antimicrob Agents Chemother

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The rise of multidrug-resistant Mycobacterium tuberculosis has complicated therapy for tuberculosis and led us to search for a potentially active combination of drugs against these strains. The susceptibilities of 12 strains of multidrug-resistant M. tuberculosis to standard antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), clarithromycin, and its metabolite, 14-hydroxyclarithromycin, were determined by use of the BACTEC radiometric method. All strains were resistant to at least two of the antituberculous drugs. Clarithromycin and 14-hydroxyclarithromycin MICs were in the range indicating resistance at >8.0 g/ml for all strains. Combination testing by the BACTEC method was performed with various concentrations of isoniazid, rifampin, and ethambutol, and with clarithromycin/14-hydroxyclarithromycin at fixed concentrations of 2.0/0.5 g/ml, respectively. Addition of clarithromycin/14-hydroxyclarithromycin to these antituberculous drug mixtures resulted in a 4-to 32-fold reduction in MICs of isoniazid, rifampin, and ethambutol and made resistant strains susceptible. Fractional inhibitory concentrations ranged from 0.23 to 0.50 for all strains, suggesting a synergistic interaction between standard antituberculous drugs and clarithromycin/14-hydroxyclarithromycin. The ability of clarithromycin/14-hydroxyclarithromycin to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections.In recent years there has been renewed interest in infections caused by Mycobacterium tuberculosis. This has been due in part to the resurgence of tuberculosis cases nationwide and an alarming increase in multidrug resistance in M. tuberculosis isolates from these infections (2,5,6,12,14,27,29). Multidrug resistance in M. tuberculosis is especially prevalent in certain geographic localities in the United States, including New York City and Florida (2,9,12,14,29). In addition, certain populations, including those infected with human immunodeficiency virus, recent immigrants to the United States, and patients with a history of treatment for tuberculosis (2,10,14,19,27), have an increased incidence. Most of these strains are resistant to the primary antituberculous drugs isoniazid and/or rifampin (2,10,12,29). Multidrug resistance complicates therapeutic options for the clinician. Indeed, patients infected with multidrug-resistant M. tuberculosis must be treated for a much longer period of time than are patients infected with susceptible strains and response rates are decreased (7,9,12,19).Clarithromycin is a new, acid-stable macrolide antibiotic which has good bioavailability after oral dosing (11,15,25). Peak serum and lung clarithromycin concentrations are 2 to 4 g/ml and 17.5 g/g, respectively (11, 15). Clarithromycin is metabolized to 14-hydroxyclarithromycin, which also has antibacterial activity and may act synergistically with the parent compound (18, 25). Clarithromycin has broad-spectr...

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“…PE is a dominant inner membrane component in E. coli (75% of total [13]), whereas Staphylococcus aureus membranes are predominantly formed from PG (ϳ90% of total [40]). In Mycobacterium tuberculosis, membranes are dominated by phosphatidylinositol mannosides (ϳ70% [51]). In many other cases, no single lipid type dominates, and in all systems there are at least three or more different types of lipid headgroups represented.…”

Section: Resultsmentioning

confidence: 99%

Phenotypic and Transcriptomic Characterization of Bacillus subtilis Mutants with Grossly Altered Membrane Composition

Salzberg

Helmann

2008

J Bacteriol

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The Bacillus subtilis membrane contains diacylglycerol-based lipids with at least five distinct headgroups that together help to define the physical and chemical properties of the lipid bilayer. Here, we describe the phenotypic characterization of mutant strains lacking one or more of the following lipids: glycolipids (ugtP mutants), phosphatidylethanolamine (pssA and psd mutants), lysylphosphatidylglycerol (mprF), and cardiolipin (ywnE and ywjE). Alterations of membrane lipid headgroup composition are generally well-tolerated by the cell, and even severe alterations lead to only modest effects on growth proficiency. Mutants with decreased levels of positively charged lipids display an increased sensitivity to cationic antimicrobial compounds, and cells lacking glycolipids are more sensitive to the peptide antibiotic sublancin and are defective in swarming motility. A quadruple mutant strain (ugtP pssA mprF ywnE), with a membrane comprised predominantly of phosphatidylglycerol, is viable and grows at near-wild-type rates, although it forms long, coiled filaments. Transcriptome comparisons identified numerous regulons with altered expression in cells of the ugtP mutant, the pssA mprF ywnE triple mutant, and the ugtP pssA mprF ywnE quadruple mutant. These effects included a general decrease in expression of the SigD and FapR regulons and increased expression of cell envelope stress responses mediated by M and the YvrGHb two-component system.

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Cell wall and membrane changes associated with ethambutol resistance in Mycobacterium tuberculosis H37Ra

Cited by 26 publications

References 21 publications

Adaptational changes in cellular phospholipids and fatty acid composition of the food pathogen Listeria monocytogenes as a stress response to disinfectant sanitizer benzalkonium chloride

Adaptational changes in cellular phospholipids and fatty acid composition of the food pathogen Listeria monocytogenes as a stress response to disinfectant sanitizer benzalkonium chloride

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

Phenotypic and Transcriptomic Characterization of Bacillus subtilis Mutants with Grossly Altered Membrane Composition

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