Modulation of Horizontal Gene Transfer in Pathogenic Bacteria by In Vivo Signals

• Published in: Cell Vol. 87; no. 5; pp. 795 - 798
• Main Authors: Mel, Stephanie F, Mekalanos, John J
• Format: Book Review Journal Article
• Language: English
• Published: United States Elsevier Inc 29.11.1996
• Subjects: Bacterial Physiological Phenomena; Conjugation, Genetic - physiology; Corynebacterium diphtheriae; Escherichia coli; Genes, Bacterial - physiology; Salmonella typhimurium; Streptococcus pneumoniae
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)81986-8

The transfer of DNA from one bacterium to another is one of several fundamental processes driving the evolution of microorganisms. In addition to the exchange of chromosomal DNA through bacterial conjugation, transformation, and transduction, accessory genetic elements such as plasmids, lysogenic bacteriophages, and conjugative transposons are also able to move between bacterial strains, leading to increased genetic diversity of bacterial populations. Horizontal DNA transfer plays a critical role in the emergence of new pathogenic organisms by the dissemination of genes encoding virulence factors (e.g., toxins, adhesions, capsules, invasion properties, etc.) and antibiotic resistance. It is becoming clear that horizontal DNA transfer between bacterial pathogens can be regulated by host factors unique to the in vivo environment of an infection. This suggests that genetic elements that are thought to be nontransmissible may in fact be transmissible if given the appropriate signals within a host environment in vivo. Pathogenic bacteria establish infections in a wide variety of host environments and specific host in vivo signals may play an important role in modulating bacterial genetic exchange. While the microenvironment of an infection is often difficult to study, it is clear that DNA transfer can occur within the host milieu. Indeed, the discovery of interbacterial gene transfer by Griffith in 1928 relied on the pneumococcus mouse infection model in which transformation was first demonstrated. As early as 1961, evidence for conjugative transfer of DNA in vivo came in a study in which a mixture of E. coli and Salmonella typhimurium strains were fed orally to mice. Within 24 hours, hybrid strains were recovered from feces and importantly, some of these recombinants were unlike any that had been observed in in vitro matings in the laboratory. This observation suggested that certain DNA transfer events may be specifically regulated and mechanistically controlled by factors found only in the host environment and not in the laboratory. Other examples of in vivo DNA transfer have been documented, such as the transmission of ENT (enterotoxin) plasmids between two E.coli strains in the intestines of newly weaned guinea pigs, the transfer of Tn916-type conjugative transposons between different genera of Gram-positive bacteria in the gastrointestinal tracts of germ-free mice, and the apparent lysogenic conversion of Corynebacterium diphtheriae in humans. While it is possible that specific host factors are regulating DNA transfer in each of these systems, such factors have not yet been identified. Here we briefly review two examples in diverse pathogen-host systems, one well-studied and one newly-discovered, in which bacterial DNA transfer is intimately coupled to eukaryotic host signals occurring locally at the site of an infection. In addition to elucidating the signaling process necessary for DNA transfer in these individual systems, the results of these studies suggest a new conceptual framework for thinking about the transfer of other genetic elements in bacterial populations.