Viable but not Culturable State​

It was once thought that a bacterial cell was dead if it couldn’t be grown on culture media. The viable but not culturable (VBNC) state is a state where bacteria can fail to grow on culture media but still be viable based on outer membrane integrity and the ability to recover growth through temperature shifts. VBNC has now been described for over 50 bacterial species. There are several mechanisms involved by which bacteria become unable to grow on certain culture media but are able to grow on other surfaces one of which is contact-dependent growth inhibition. The mechanism is not well understood.

Contact-dependent Growth Inhibition

Another phenomenon has been observed such that cell growth is controlled by direct cell-to-cell contact mediated by the CdiA-CdiB two-partner secretion (TPS) system. CdiA-CdiB is present in certain E. coli strains and homologous proteins are found in many bacterial species. By homology with other TPS systems, CdiB appears to be an outer membrane protein required for the transport and assembly of CdiA at the cell surface. The CDI receptor has been identified as BamA also known as YaeT, which is an essential, highly conserved outer membrane protein required for the biogenesis of beta-barrel proteins in gram-negative bacteria. Concomitant with a block in cell growth, CDI induces significant reductions in respiration, proton-motive force, and ATP levels. The mechanism that connects interaction with BamA at the cell surface to down-regulation of metabolism is unclear, but it may involve the inner membrane multi-drug resistance protein AcrB since acrB mutants are resistant to CDI. One possibility is that CdiA interacts with AcrB through BamA to modulate its activity. AcrB exploits the proton-motive force to couple proton import to the export of small toxic molecules. Thus CdiA could induce AcrB to open its proton channel and dissipate the proton motive force. This speculative model for the CDI mechanism follows.

Alternate genetic expression may be involved in contact-dependent changes in metabolism and growth in bacteria. There is another aspect to the CDI mechanism. There happens to be an open frame that overlaps with CdiA that encodes for a small protein called CdiI that brings about immunity to CDI. Genetic expression of CdiI in target cells protects against CDI+ inhibitor cells. The small protein CdiI also protects CDI+ cells from inhibiting their own growth. It has been suggested that CDI could be a counter-surveillance mechanism allowing bacteria to literally hid-out within host tissues since they are metabolically down-regulated. It has also been suggested that CDI cells may act as a bacterial warfare system by inhibiting growth of neighboring bacterial cells. This might work well in biofilms.

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