AI-2 production is indeed present in the genome of more
than 60 species (Proteobacteria, Spirochaetes, Firmicutes,
etc.), suggesting that AI-2 could be part of an interspecies
language (Xavier and Bassler 2003). The LuxS/AI-2
system was analyzed in Vibrio, including V. harveyi and
V. cholerae, where it helps regulate bioluminescence and
the production of virulence factors. However, the precise
role of AI-2 in other species remains controversial, partly
because LuxS also plays a metabolic role in the activated
methyl cycle (Williams et al. 2007).
Given the large number of extracellular bacterial
metabolites and the low proportion of bacteria that are
culturable in the laboratory, it is likely that the diversity of
QS molecules known to date represents only the “tip of the
iceberg.”
The term “quorum sensing” does not describe satisfactorily
all the situations in which bacteria use diffusible compounds.
In the case of AHLs, the quorum size is not defined and
may vary depending on the spatial distribution of cells, rates
of synthesis, and loss (by degradation or diffusion). Hence,
the notion of “efficiency sensing” was proposed (Hense et al.
2007): autoinducers produced in the environment would have
a role of proxy in assessing the effectiveness of producing
extracellular costly effectors (such as exoenzymes).
In pathogenic bacteria, bacterial communication provides a new target for novel antibacterials; while
conventional antibiotics target bacterial growth and lead
to the emergence of resistant bacteria, using molecules
that block the QS could precisely target pathogenesis
(Bjarnsholt and Givskov 2007). Thus, many studies currently aim at identifying natural QS inhibitors, especially
from plants, or at developing synthetic QS inhibitors
(Chung et al. 2011).
9.4
Phase Variation*
9.4.1 Phase Variation and Antigenic Variation
One of the clearest manifestations of the phase variation
phenomenon is the appearance of a minority of colonies or
sectors of colonies having a different appearance on agar.
Phase variation or phenotypic conversion leads to the coexistence within the same population of different cell types
(wild type and variants), some of which may have a significant selective advantage under some physicochemical
conditions. Through phase variation, the expression of a
given phenotype is either turned “ON” or turned “OFF”;
these events are generally reversible (“ON” $ “OFF”) but
can be irreversible (“ON” ! “OFF” or “OFF” ! “ON”)
and result from genetic or epigenetic alterations at specific
loci (van der Woude and Baumler 2004; Wisniewski-Dye ´
and Vial 2008).
In contrast to spontaneous mutations which occur at a
frequency of about 10
–8 to 10
–6 mutations per growing cell
per generation, phase variation occurs at a frequency higher
than 10
–5 events per cell per generation and always affects
the same phenotype(s). Phase variation has been described
for many different bacterial genera belonging to diverse
taxonomic groups and displaying various lifestyles
(pathogens, saprophytes, symbionts). It contributes to regulate many phenotypes: synthesis of pili, flagella, surface
lipoproteins, secondary metabolites, etc.
Antigenic variation refers to the expression of a number
of alternative forms of a cell surface antigen (lipoproteins,
pili, etc.); this generates within a clonal population, individual cells that are antigenically distinct, allowing bacterial
pathogens to escape the host immune system. At the molecular level, certain mechanisms of antigenic variation have
common features with mechanisms of phase variation.
9.4.2 Phase Variation Through Modification
of the Genome
9.4.2.1 Gene Conversion*
This gene conversion mechanism, extensively documented
for antigenic variation, implies a recombination event
between a silent copy of a gene and another copy that is
expressed, leading to a new chimeric gene. When several
copies of the silent gene are present, many chimeric
sequences can be theoretically generated, which allows the
expression of various forms of a given antigen. There is no
common mechanism for gene conversion, but in some cases,
proteins of the homologous recombination pathway are
involved. One of the best documented cases of gene conversion concerns type IV pili in the human pathogen Neisseria
gonorrhoeae; this phenomenon generates multiple antigenic
forms of pilin (Howell-Adams and Seifert 2000).
9.4.2.2 Site-Specific Inversion
This process involves specific enzymes (recombinases)
and requires short homologous regions. These recombinases
recognize inverted repeat sequences (IR) located on either
side of the element to be inverted. Most inversion systems
are independent of RecA activity. However, antigenic variation of surface layer proteins (SLP) in Campylobacter fetus
via an inversion event requires the action of RecA.
Campylobacter fetus, an opportunistic parasite of humans
and animals that interferes with reproductive functions,
possesses eight SLP gene cassettes, clustered on the chromosome, encoding proteins of 97–149 kDa. All these
9 Adaptations of Prokaryotes to Their Biotopes and to Physicochemical Conditions. . .
317
than 60 species (Proteobacteria, Spirochaetes, Firmicutes,
etc.), suggesting that AI-2 could be part of an interspecies
language (Xavier and Bassler 2003). The LuxS/AI-2
system was analyzed in Vibrio, including V. harveyi and
V. cholerae, where it helps regulate bioluminescence and
the production of virulence factors. However, the precise
role of AI-2 in other species remains controversial, partly
because LuxS also plays a metabolic role in the activated
methyl cycle (Williams et al. 2007).
Given the large number of extracellular bacterial
metabolites and the low proportion of bacteria that are
culturable in the laboratory, it is likely that the diversity of
QS molecules known to date represents only the “tip of the
iceberg.”
The term “quorum sensing” does not describe satisfactorily
all the situations in which bacteria use diffusible compounds.
In the case of AHLs, the quorum size is not defined and
may vary depending on the spatial distribution of cells, rates
of synthesis, and loss (by degradation or diffusion). Hence,
the notion of “efficiency sensing” was proposed (Hense et al.
2007): autoinducers produced in the environment would have
a role of proxy in assessing the effectiveness of producing
extracellular costly effectors (such as exoenzymes).
In pathogenic bacteria, bacterial communication provides a new target for novel antibacterials; while
conventional antibiotics target bacterial growth and lead
to the emergence of resistant bacteria, using molecules
that block the QS could precisely target pathogenesis
(Bjarnsholt and Givskov 2007). Thus, many studies currently aim at identifying natural QS inhibitors, especially
from plants, or at developing synthetic QS inhibitors
(Chung et al. 2011).
9.4
Phase Variation*
9.4.1 Phase Variation and Antigenic Variation
One of the clearest manifestations of the phase variation
phenomenon is the appearance of a minority of colonies or
sectors of colonies having a different appearance on agar.
Phase variation or phenotypic conversion leads to the coexistence within the same population of different cell types
(wild type and variants), some of which may have a significant selective advantage under some physicochemical
conditions. Through phase variation, the expression of a
given phenotype is either turned “ON” or turned “OFF”;
these events are generally reversible (“ON” $ “OFF”) but
can be irreversible (“ON” ! “OFF” or “OFF” ! “ON”)
and result from genetic or epigenetic alterations at specific
loci (van der Woude and Baumler 2004; Wisniewski-Dye ´
and Vial 2008).
In contrast to spontaneous mutations which occur at a
frequency of about 10
–8 to 10
–6 mutations per growing cell
per generation, phase variation occurs at a frequency higher
than 10
–5 events per cell per generation and always affects
the same phenotype(s). Phase variation has been described
for many different bacterial genera belonging to diverse
taxonomic groups and displaying various lifestyles
(pathogens, saprophytes, symbionts). It contributes to regulate many phenotypes: synthesis of pili, flagella, surface
lipoproteins, secondary metabolites, etc.
Antigenic variation refers to the expression of a number
of alternative forms of a cell surface antigen (lipoproteins,
pili, etc.); this generates within a clonal population, individual cells that are antigenically distinct, allowing bacterial
pathogens to escape the host immune system. At the molecular level, certain mechanisms of antigenic variation have
common features with mechanisms of phase variation.
9.4.2 Phase Variation Through Modification
of the Genome
9.4.2.1 Gene Conversion*
This gene conversion mechanism, extensively documented
for antigenic variation, implies a recombination event
between a silent copy of a gene and another copy that is
expressed, leading to a new chimeric gene. When several
copies of the silent gene are present, many chimeric
sequences can be theoretically generated, which allows the
expression of various forms of a given antigen. There is no
common mechanism for gene conversion, but in some cases,
proteins of the homologous recombination pathway are
involved. One of the best documented cases of gene conversion concerns type IV pili in the human pathogen Neisseria
gonorrhoeae; this phenomenon generates multiple antigenic
forms of pilin (Howell-Adams and Seifert 2000).
9.4.2.2 Site-Specific Inversion
This process involves specific enzymes (recombinases)
and requires short homologous regions. These recombinases
recognize inverted repeat sequences (IR) located on either
side of the element to be inverted. Most inversion systems
are independent of RecA activity. However, antigenic variation of surface layer proteins (SLP) in Campylobacter fetus
via an inversion event requires the action of RecA.
Campylobacter fetus, an opportunistic parasite of humans
and animals that interferes with reproductive functions,
possesses eight SLP gene cassettes, clustered on the chromosome, encoding proteins of 97–149 kDa. All these
9 Adaptations of Prokaryotes to Their Biotopes and to Physicochemical Conditions. . .
317