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Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance

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Peptidoglycan forms the stress-bearing sacculus that prevents lysis of bacteria due to turgor pressure. The integrity of peptidoglycan is therefore essential for bacterial survival and its synthesis is the target of many important antibiotics, such as penicillin. The final steps of peptidoglycan synthesis are catalyzed by penicillin-binding proteins, enzymes that are proposed to work in multi-enzyme complexes. We show that seven of the nine genes encoding peptidoglycan synthesis enzymes can be deleted from the Staphylococcus aureus genome without affecting normal growth and cell morphology in vitro, identifying the minimal peptidoglycan synthesis machinery of this organism. Identification of minimal machineries is key for synthetic biology efforts towards the design of systems with reduced complexity. However, the non-essential peptidoglycan synthetic proteins are important for survival of S. aureus in more challenging environments, such as in the presence of antibiotics that target cell wall synthesis or within the host, as shown by the inability of the mutant strain to establish a successful infection and kill Drosophila flies.

Vyšlo v časopise: Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004891
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004891

Souhrn

Peptidoglycan forms the stress-bearing sacculus that prevents lysis of bacteria due to turgor pressure. The integrity of peptidoglycan is therefore essential for bacterial survival and its synthesis is the target of many important antibiotics, such as penicillin. The final steps of peptidoglycan synthesis are catalyzed by penicillin-binding proteins, enzymes that are proposed to work in multi-enzyme complexes. We show that seven of the nine genes encoding peptidoglycan synthesis enzymes can be deleted from the Staphylococcus aureus genome without affecting normal growth and cell morphology in vitro, identifying the minimal peptidoglycan synthesis machinery of this organism. Identification of minimal machineries is key for synthetic biology efforts towards the design of systems with reduced complexity. However, the non-essential peptidoglycan synthetic proteins are important for survival of S. aureus in more challenging environments, such as in the presence of antibiotics that target cell wall synthesis or within the host, as shown by the inability of the mutant strain to establish a successful infection and kill Drosophila flies.

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