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- W2893443791 abstract "Spores are produced by many organisms as a survival mechanism activated in response to several environmental stresses. Bacterial spores are multilayered structures, one of which is a peptidoglycan layer called the cortex, containing muramic-δ-lactams that are synthesized by at least two bacterial enzymes, the muramoyl-l-alanine amidase CwlD and the N-deacetylase PdaA. This study focused on the spore cortex of Clostridium difficile, a Gram-positive, toxin-producing anaerobic bacterial pathogen that can colonize the human intestinal tract and is a leading cause of antibiotic-associated diarrhea. Using ultra-HPLC coupled with high-resolution MS, here we found that the spore cortex of the C. difficile 630Δerm strain differs from that of Bacillus subtilis. Among these differences, the muramic-δ-lactams represented only 24% in C. difficile, compared with 50% in B. subtilis. CD630_14300 and CD630_27190 were identified as genes encoding the C. difficile N-deacetylases PdaA1 and PdaA2, required for muramic-δ-lactam synthesis. In a pdaA1 mutant, only 0.4% of all muropeptides carried a muramic-δ-lactam modification, and muramic-δ-lactams were absent in the cortex of a pdaA1–pdaA2 double mutant. Of note, the pdaA1 mutant exhibited decreased sporulation, altered germination, decreased heat resistance, and delayed virulence in a hamster infection model. These results suggest a much greater role for muramic-δ-lactams in C. difficile than in other bacteria, including B. subtilis. In summary, the spore cortex of C. difficile contains lower levels of muramic-δ-lactams than that of B. subtilis, and PdaA1 is the major N-deacetylase for muramic-δ-lactam biosynthesis in C. difficile, contributing to sporulation, heat resistance, and virulence. Spores are produced by many organisms as a survival mechanism activated in response to several environmental stresses. Bacterial spores are multilayered structures, one of which is a peptidoglycan layer called the cortex, containing muramic-δ-lactams that are synthesized by at least two bacterial enzymes, the muramoyl-l-alanine amidase CwlD and the N-deacetylase PdaA. This study focused on the spore cortex of Clostridium difficile, a Gram-positive, toxin-producing anaerobic bacterial pathogen that can colonize the human intestinal tract and is a leading cause of antibiotic-associated diarrhea. Using ultra-HPLC coupled with high-resolution MS, here we found that the spore cortex of the C. difficile 630Δerm strain differs from that of Bacillus subtilis. Among these differences, the muramic-δ-lactams represented only 24% in C. difficile, compared with 50% in B. subtilis. CD630_14300 and CD630_27190 were identified as genes encoding the C. difficile N-deacetylases PdaA1 and PdaA2, required for muramic-δ-lactam synthesis. In a pdaA1 mutant, only 0.4% of all muropeptides carried a muramic-δ-lactam modification, and muramic-δ-lactams were absent in the cortex of a pdaA1–pdaA2 double mutant. Of note, the pdaA1 mutant exhibited decreased sporulation, altered germination, decreased heat resistance, and delayed virulence in a hamster infection model. These results suggest a much greater role for muramic-δ-lactams in C. difficile than in other bacteria, including B. subtilis. In summary, the spore cortex of C. difficile contains lower levels of muramic-δ-lactams than that of B. subtilis, and PdaA1 is the major N-deacetylase for muramic-δ-lactam biosynthesis in C. difficile, contributing to sporulation, heat resistance, and virulence." @default.
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- W2893443791 date "2018-11-01" @default.
- W2893443791 modified "2023-09-29" @default.
- W2893443791 title "N-Deacetylases required for muramic-δ-lactam production are involved in Clostridium difficile sporulation, germination, and heat resistance" @default.
- W2893443791 cites W1540533589 @default.
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- W2893443791 cites W1578684107 @default.
- W2893443791 cites W1655185245 @default.
- W2893443791 cites W1916481354 @default.
- W2893443791 cites W1970394313 @default.
- W2893443791 cites W1977916453 @default.
- W2893443791 cites W1978693132 @default.
- W2893443791 cites W1980238990 @default.
- W2893443791 cites W1981549920 @default.
- W2893443791 cites W1981701430 @default.
- W2893443791 cites W1982660404 @default.
- W2893443791 cites W1986945525 @default.
- W2893443791 cites W1990908229 @default.
- W2893443791 cites W2007358645 @default.
- W2893443791 cites W2007890464 @default.
- W2893443791 cites W2009691601 @default.
- W2893443791 cites W2010470461 @default.
- W2893443791 cites W2011299520 @default.
- W2893443791 cites W2012464397 @default.
- W2893443791 cites W2013798205 @default.
- W2893443791 cites W2015557312 @default.
- W2893443791 cites W2016313746 @default.
- W2893443791 cites W2037583354 @default.
- W2893443791 cites W2038231155 @default.
- W2893443791 cites W2040992902 @default.
- W2893443791 cites W2043145584 @default.
- W2893443791 cites W2047821263 @default.
- W2893443791 cites W2060417514 @default.
- W2893443791 cites W2063214527 @default.
- W2893443791 cites W2071054182 @default.
- W2893443791 cites W2088710570 @default.
- W2893443791 cites W2091290075 @default.
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- W2893443791 cites W2129239939 @default.
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- W2893443791 doi "https://doi.org/10.1074/jbc.ra118.004273" @default.
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