Loss of low-level antibiotic resistance in Neisseria gonorrhoeae due to env mutations

Sarubbi, Felix A.; Sparling, P. Frederick; Blackman, E; Lewis, E. B.

doi:10.1128/jb.124.2.750-756.1975

Cited by 55 publications

(52 citation statements)

References 17 publications

(33 reference statements)

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“…The acquisition of env loci, which results in an increased sensitivity to various hydrophobic molecules (21), also results in an increased sensitivity to steroid hormones. The presence of the penA2 locus, which specifically increases penicillin resistance (23), does not confer resistance to steroid inhibition of 02 uptake.…”

Section: Discussionmentioning

confidence: 99%

“…Organisms and growth conditions. The isogenic strains of N. gonorrhoeae used in these experiments were kindly provided by P. F. Sparling (University of North Carolina, Chapel Hill) and are listed in Table 1. The origin, genotype, and sensitivities of these strains to antibiotics, dyes, and detergents have previously been described (7,21,23). Cells of colony type 4, which were nonpiliated and transparent (P-Tr), were used in all experiments.…”

Section: Methodsmentioning

confidence: 99%

“…These data suggest that the permeability of the gonococcus to hydrophobic antibiotic and steroid molecules is mediated by the degree of phospholipid exposure on the outer membrane. The genetics of low-level antibiotic resistance and hypersensitivity in Neisseria gonorrhoeae has been well described (12,20,21,23). Loci designated as penA, mtr, and penB contribute additively to penicillin resistance, whereas env mutations suppress the phenotypic properties of mtr and penB.…”

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confidence: 99%

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Neisseria gonorrhoeae cell envelope: permeability to hydrophobic molecules

Lysko¹,

Morse²

1981

J Bacteriol

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Isogenic variants of antibiotic-resistant and -sensitive Neisseria gonorrhoeae were examined for differences in the inhibition of oxygen uptake by steroid hormones. Mutants designated as env, which possessed cell envelope mutations allowing phenotypic suppression of low-level antibiotic resistance, were more sensitive to steroid hormone inhibition of oxygen uptake than the wild-type parental strains. Possession of an mtr locus, which confers nonspecific resistance to multiple antibiotics, dyes, and detergents, was also associated with an increase in resistance to steroid hormone inhibition of oxygen uptake. The penA2 locus, which confers an eightfold increase in resistance to penicillin, was not responsible for the increased resistance to steroid hormones. Phospholipids in the outer membrane of intact env-2 cells were susceptible to digestion by phospholipase C, indicating exposure of phospholipid head groups on the outer surface. Cells of a wild-type and mtr-2 strain were not susceptible to phospholipase C digestion unless they were pretreated with mixed exoglycosidases. This pretreatment also increased the sensitivity of mtr-2 cells to progesterone inhibition of 02 uptake. These data suggest that the permeability of the gonococcus to hydrophobic antibiotic and steroid molecules is mediated by the degree of phospholipid exposure on the outer membrane.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Neisseria gonorrhoeae cell envelope: permeability to hydrophobic molecules

Lysko¹,

Morse²

1981

J Bacteriol

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“…Previous reports from this laboratory (46,51) and others (30) have described the genetics of antibiotic resistance in Neisseria gonorrhoeae. Penicillin resistance is acquired in discrete steps, with several genes contributing to penicillin resistance in an additive manner.…”

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confidence: 91%

Cell envelope alterations in antibiotic-sensitive and-resistant strains of Neisseria gonorrhoeae

Guymon¹,

Walstad²,

Sparling³

1978

J Bacteriol

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The cell envelopes of antibiotic-resistant and -sensitive isogenic strains of Neisseria gonorrhoeae were analyzed to determine whether acquisition of genetic loci for altered antibiotic sensitivity was accompanied by alterations in cell envelope composition. No differences in the composition of phospholipids and lipopolysaccharides were noted. Acquisition of mtr-2, which results in low-level, nonspecific increased resistance to multiple antibiotics, dyes, and detergents, was accompanied by a sevenfold increase in the amount of a minor, 52,000-molecularweight outer membrane protein and a 32% increase in the extent of peptidoglycan cross-linking. Subsequent addition of the nonspecific hypersensitivity loci env-1 or env-2 to a strain carrying mtr-2 resulted in reversal of the phenotypic resistance determined by mtr-2 and marked reduction in both the amount of the 52,000molecular-weight outer membrane protein and the extent of peptidoglycan crosslinking. Introduction of penB2, which results in a fourfold increase in resistance to penicillin and tetracycline, was accompanied by the disappearance of the principal outer membrane protein of the wild-type strain (molecular weight, 36,900) and the appearance of a new species of the principal outer membrane protein (molecular weight, 39,400) in the transformant. MATERIALS AND METHODSStrains used. The strains used in these studies 391 on July 16, 2020 by guest

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“…The extraction of gonococcal phospholipids by Triton X-100 is in agreement with the observation that the growth of gonococci is inhibited by low concentrations. of this detergent (26), whereas the growth of enteric bacteria is not. The stimulation of phospholipid hydrolysis by methanol may be due to increased accessibility of the enzyme to divalent cations and to fatty acid acyl chains of phospholipids.…”

Section: Discussionmentioning

confidence: 95%

Phospholipid metabolism inNeisseria gonorrhoeae: Phospholipid hydrolysis in nongrowing cells

Cacciapuoti

Wegener

Morse

1979

Lipids

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Hydrolysis of cell envelope phospholipids was demonstrated in cells of both autolytic and nonautolytic strains of Neisseria gonorrhoeae that were labeled during growth in the presence of [3H] acetate. The label incorporated into the cellular phospholipids was located exclusively in the fatty acid acyl side chains. Labeled cells were incubated for 2 hr in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, pH 8.5, containing various additions, and then examined for distribution of 3H in lipids. Ca++ selectively stimulated the deacylation of phosphatidylethanolamine (PE), whereas Mn++ stimulated the deacylation of phosphatidylglycerol (PG). Hydrolysis of phosphatidylethanolamine by phospholipase A was accompanied by the accumulation of lysophosphatidylethanolamine (LPE) and free fatty acids in the cells. Free fatty acids accumulated to a greater extent than lysophosphatidylethanolamine, suggesting that the latter was further hydrolyzed to glycerophosphorylethanolamine (GPE) and free fatty acids by a lysophospholipase. Methanol, ethanol, propanol, and isopropanol, added at concentrations which inhibited growth by 50%, stimulated phospholipase A, but not lysophospholipase activity. Differences in heat inactivation, metal ion requirements, and pH optima suggested that phospholipase A activities with phosphatidylethanolamine or phosphatidylglycerol as substrate and lysophospholipase may be separate enzymes.

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Loss of low-level antibiotic resistance in Neisseria gonorrhoeae due to env mutations

Cited by 55 publications

References 17 publications

Neisseria gonorrhoeae cell envelope: permeability to hydrophobic molecules

Neisseria gonorrhoeae cell envelope: permeability to hydrophobic molecules

Cell envelope alterations in antibiotic-sensitive and-resistant strains of Neisseria gonorrhoeae

Phospholipid metabolism inNeisseria gonorrhoeae: Phospholipid hydrolysis in nongrowing cells

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