femA, which encodes a factor essential for expression of methicillin resistance, affects glycine content of peptidoglycan in methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains.
femA is a chromosomally encoded factor, occurring naturally in Staphylococcus aureus, which is essential for the expression of high-level methicillin resistance in this organism. The production of a low-affinity penicillin-binding protein, PBP2a or PBP2', which is intimately involved with methicillin resistance in S. aureus, is not influenced by femA. To elucidate a possible physiological function of the 48-kDa protein encoded by femA, several related methicillin-resistant, methicillin-susceptible, and Tn551 insertionally inactivated femA mutants were analyzed for possible changes in cell wall structure and metabolism. Independent of the presence of mec, the methicillin resistance determinant, all femA mutants had a reduced peptidoglycan (PG) glycine content (up to 60% in the molar ratio of glycine/glutamic acid) compared to that of related femA+ parent strains. Additional effects of femA inactivation and the subsequent decrease in PG-associated glycine were (i) reduced digestion of PG by recombinant lysostaphin, (ii) unaltered digestion of PG by Chalaropsis B-muramidase, (iii) reduced cell wall turnover, (iv) reduced whole-cell autolysis, and (v) increased sensitivity towards beta-lactam antibiotics. Also, the PG-associated glycine content of a femA::Tn551 methicillin-susceptible strain was restored concomitantly with the methicillin resistance to a level almost equal to that of its femA+ methicillin-resistant parent strain by introduction of plasmid pBBB31, encoding femA.
Maidhof
H
H
Robert Koch-Institute of the Federal Health Office, Berlin, Germany.
Reinicke
B
B
Blümel
P
P
Berger-Bächi
B
B
Labischinski
H
H
D000117:Acetylglucosamine / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D015139:Blotting, Southern; D002473:Cell Wall / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D005798:Genes, Bacterial; D005998:Glycine / Q000378:metabolism*; D008712:Methicillin; D010457:Peptidoglycan / Q000032:analysis; D010957:Plasmids; D015183:Restriction Mapping; D013211:Staphylococcus aureus / Q000235:genetics*; D014161:Transduction, Genetic
D000596:Amino Acids; D010457:Peptidoglycan; D008712:Methicillin; D005998:Glycine; D000117:Acetylglucosamine