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Actin Polymerization Drives Septation of Listeria monocytogenes namA Hydrolase Mutants, Demonstrating Host Correction of a Bacterial Defect

Author:
Alonzo, Francis III., McMullen, P. David, Freitag, Nancy E.
Source:
Infection and immunity 2011 v.79 no.4 pp. 1458-1470
ISSN:
0019-9567
Subject:
Gram-positive bacteria, Listeria monocytogenes, Nama, actin, cell division, cell walls, coculture, cytochalasin D, cytosol, drugs, mice, microbial growth, mutants, peptidoglycans, polymerization, protein secretion, soil, virulence
Abstract:
The Gram-positive bacterial cell wall presents a structural barrier that requires modification for protein secretion and large-molecule transport as well as for bacterial growth and cell division. The Gram-positive bacterium Listeria monocytogenes adjusts cell wall architecture to promote its survival in diverse environments that include soil and the cytosol of mammalian cells. Here we provide evidence for the enzymatic flexibility of the murein hydrolase NamA and demonstrate that bacterial septation defects associated with a loss of NamA are functionally complemented by physical forces associated with actin polymerization within the host cell cytosol. L. monocytogenes ΔnamA mutants formed long bacterial chains during exponential growth in broth culture; however, normal septation could be restored if mutant cells were cocultured with wild-type L. monocytogenes bacteria or by the addition of exogenous NamA. Surprisingly, ΔnamA mutants were not significantly attenuated for virulence in mice despite the pronounced exponential growth septation defect. The physical force of L. monocytogenes-mediated actin polymerization within the cytosol was sufficient to sever ΔnamA mutant intracellular chains and thereby enable the process of bacterial cell-to-cell spread so critical for L. monocytogenes virulence. The inhibition of actin polymerization by cytochalasin D resulted in extended intracellular bacterial chains for which septation was restored following drug removal. Thus, despite the requirement for NamA for the normal septation of exponentially growing L. monocytogenes cells, the hydrolase is essentially dispensable once L. monocytogenes gains access to the host cell cytosol. This phenomenon represents a notable example of eukaryotic host cell complementation of a bacterial defect.
Agid:
290648