Natural Transformation and Phase Variation Modulation in Neisseria Meningitidis

Mol Microbiol. 2004 May;52(3):771-83. doi: 10.1111/j.1365-2958.2004.04013.x.


Neisseria meningitidis has evolved the ability to control the expression-state of numerous genes by phase variation. It has been proposed that the process aids this human pathogen in coping with the diversity of microenvironments and host immune systems. Therefore, increased frequencies of phase variation may augment the organism's adaptability and virulence. In this study, we found that DNA derived from various neisserial co-colonizers of the human nasopharynx increased N. meningitidis switching frequencies, indicating that heterologous neisserial DNA modulates phase variation in a transformation-dependent manner. In order to determine whether the effect of heterologous DNA was specific to the Hb receptor, HmbR, we constructed a Universal Rates of Switching cassette (UROS). With this cassette, we demonstrated that heterologous DNA positively affects phase variation throughout the meningococcal genome, as UROS phase variation frequencies were also increased in the presence of neisserial DNA. Overexpressing components of the neisserial mismatch repair system partially alleviated DNA-induced changes in phase variation frequencies, thus implicating mismatch repair titration as a cause of these transformation-dependent increases in switching. The DNA-dependent effect on phase variation was transient and may serve as a mechanism for meningococcal genetic variability that avoids the fitness costs encountered by global mutators.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Base Pair Mismatch
  • DNA Repair
  • Genetic Variation*
  • Humans
  • Molecular Sequence Data
  • Neisseria meningitidis / genetics*
  • Neisseria meningitidis / physiology
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Transformation, Bacterial*


  • Bacterial Proteins
  • HmbR protein, Neisseria meningitidis
  • Protein Subunits
  • Receptors, Cell Surface