(Qiu et al. 2006). PAPI-1 was classified in the group of
mobile elements termed “ICE” that encodes integration
and conjugative properties (Burrus and Waldor 2004).
Phylogenetic analyses suggest PAI distribution to be
mainly genus or species specific. However, a transfer of
the SaPI1 PAI by a bacteriophage was demonstrated
between S. aureus and Listeria monocytogenes (Chen and
Novick 2009). This suggests that the environmental cycle of
these pathogenic bacteria may represent an opportunity to
acquire PAI from a wide range of eubacteria. Thousands of
species of bacteria can be found per gram of soil or milliliter
of water and be reservoirs of PAI. Nevertheless, many PAI
do not harbor elements that could trigger their transfer.
The absence of a transfer function in some PAI may be an
indication of an ancient acquisition. These PAI might have
been subjected to genetic purges and selective rearrangements leading to a counterselection of genes having
low benefits. Indeed, it seems that mobility could be a
counterselected trait under some circumstances if other
functions encoded by the PAI confer selective advantages
under a greater genomic stability. An example of such
a situation could be the one of the ExoU island of
P. aeruginosa (Kulasekara et al. 2006). The evolutionary
history of this PAI suggests a transposition event leading to
the presence of the exoU gene onto an ICE. This ICE would
have been acquired by P. aeruginosa and been integrated
into a tRNA gene. Subsequently, this ICE would have been
affected by multiple rearrangements leading to a loss of
mobility. Many other PAI were found to match this kind of
configuration. We can cite HP1 of Yersinia pestis; PAI I 536 ,
II 536 , III 536 , and IV 536 of uropathogenic E. coli (UPEC); LIPI
2 of Listeria ivanovii; etc. (Hacker and Kaper 2000).
Nowadays, the GI concept was enriched by extending
its range of functional benefits to other contexts than
virulence. This extension was performed on the basis of
observations made on full genome DNA sequences of nonpathogenic bacteria. These genomes were found to harbor
genomic islands with configurations similar to those of PAI
but without the presence of virulence genes. These GI are
sometimes referred to as ecological islands (EI) because they
were found to play part in the environmental degradation of
phenols or the assimilation of sugars. These can also be
termed symbiotic islands when they contribute to the establishment of symbiotic associations with other organisms such
as plants. Some of these “ecological” GI can be found among
pathogens and could play part in their environmental cycle.
15.3.6 Antibiotic Use and the Fight Against
Bacterial Infectious Disease
The discovery of antibiotics and their introduction in clinical
practices was a therapeutic revolution and contributed to
lower mortality due to infectious diseases (diphtheria,
plague, typhoid, tuberculosis, leprosy, meningitis, syphilis,
etc.). Penicillin and streptomycin used in the 1940s followed
by the golden era of discovery of novel antibiotics classes
between the 1950s and 1970s had raised many hopes in the
fight against infectious diseases. However during these
last 60 years, we observed an increase of the number and
diversity of the species developing antibiotic resistance. The
emergence of bacterial resistances is preferentially made in a
context of disadvantaged social circles, the poverty favoring
self-medication, the use of out-of-date antibiotics, and consequently an often inappropriate consumption. In parallel the
intensive use of antibiotics in the hospitals of the western
countries, but also in the context of practices without any
therapeutic aims (i.e., prophylactic purposes and stimulation
of animal growth), associated with an increase of immunocompromised individuals participates in the emergence and
spread of antibiotic resistance.
15.3.6.1 Emergence and Spread of Antibiotic
Resistance Among Bacterial Pathogens
Adaptation and Spread Mechanisms
Antibiotics are categorized as bacteriostatic (i.e., growth
inhibition) or bactericidal (i.e., cell death) and show a
narrow or wide range of activity toward bacterial species.
Basic mechanisms of antibiotic action against bacterial cells
are inhibition of cell wall synthesis (penicillin, cephalosporin, or vancomycin), of protein synthesis (chloramphenicol, streptomycin, tetracycline), of nucleic acid synthesis
(quinolones), or of metabolic processes (sulfonamides).
Bacterial species differ in terms of their sensitivity toward
antibiotics, some exhibiting a high level of intrinsic resistance. Enhanced resistance toward an antibiotic or resistance
toward new antibiotic can also be acquired through
gene mutation or gain of new genes. Resistance mechanisms
and genetic determinants have been widely investigated,
and many of them have been identified (Levy and Marshall
2004). There are several molecular mechanisms that
include modifying or protecting the target, reducing the
membrane permeability, inactivating the antibiotic through
enzyme activity, or actively exporting an antibiotic from the
bacterial cell (efflux pump). These mechanisms are more or
less specific of an antibiotic and can act simultaneously.
Dissemination of resistance is mediated by clonal spread of
a particular resistant strain and/or by spreading of resistance
genes through horizontal gene transfer. The former is the
main explanation for the first resistance described within
bacterial pathogenic species. The latter was further involved
in the spread of resistance between taxonomically distantly
related species (Martinez et al. 2009). The location of
resistance genes on plasmids or transposons contributes to
intercellular transfer. These genes are also often associated
to integrons*, which capture genes by site-specific recombination, allowing intracellular mobility then favoring
multiresistance acquisition.
15 Environmental and Human Pathogenic Microorganisms
635
mobile elements termed “ICE” that encodes integration
and conjugative properties (Burrus and Waldor 2004).
Phylogenetic analyses suggest PAI distribution to be
mainly genus or species specific. However, a transfer of
the SaPI1 PAI by a bacteriophage was demonstrated
between S. aureus and Listeria monocytogenes (Chen and
Novick 2009). This suggests that the environmental cycle of
these pathogenic bacteria may represent an opportunity to
acquire PAI from a wide range of eubacteria. Thousands of
species of bacteria can be found per gram of soil or milliliter
of water and be reservoirs of PAI. Nevertheless, many PAI
do not harbor elements that could trigger their transfer.
The absence of a transfer function in some PAI may be an
indication of an ancient acquisition. These PAI might have
been subjected to genetic purges and selective rearrangements leading to a counterselection of genes having
low benefits. Indeed, it seems that mobility could be a
counterselected trait under some circumstances if other
functions encoded by the PAI confer selective advantages
under a greater genomic stability. An example of such
a situation could be the one of the ExoU island of
P. aeruginosa (Kulasekara et al. 2006). The evolutionary
history of this PAI suggests a transposition event leading to
the presence of the exoU gene onto an ICE. This ICE would
have been acquired by P. aeruginosa and been integrated
into a tRNA gene. Subsequently, this ICE would have been
affected by multiple rearrangements leading to a loss of
mobility. Many other PAI were found to match this kind of
configuration. We can cite HP1 of Yersinia pestis; PAI I 536 ,
II 536 , III 536 , and IV 536 of uropathogenic E. coli (UPEC); LIPI
2 of Listeria ivanovii; etc. (Hacker and Kaper 2000).
Nowadays, the GI concept was enriched by extending
its range of functional benefits to other contexts than
virulence. This extension was performed on the basis of
observations made on full genome DNA sequences of nonpathogenic bacteria. These genomes were found to harbor
genomic islands with configurations similar to those of PAI
but without the presence of virulence genes. These GI are
sometimes referred to as ecological islands (EI) because they
were found to play part in the environmental degradation of
phenols or the assimilation of sugars. These can also be
termed symbiotic islands when they contribute to the establishment of symbiotic associations with other organisms such
as plants. Some of these “ecological” GI can be found among
pathogens and could play part in their environmental cycle.
15.3.6 Antibiotic Use and the Fight Against
Bacterial Infectious Disease
The discovery of antibiotics and their introduction in clinical
practices was a therapeutic revolution and contributed to
lower mortality due to infectious diseases (diphtheria,
plague, typhoid, tuberculosis, leprosy, meningitis, syphilis,
etc.). Penicillin and streptomycin used in the 1940s followed
by the golden era of discovery of novel antibiotics classes
between the 1950s and 1970s had raised many hopes in the
fight against infectious diseases. However during these
last 60 years, we observed an increase of the number and
diversity of the species developing antibiotic resistance. The
emergence of bacterial resistances is preferentially made in a
context of disadvantaged social circles, the poverty favoring
self-medication, the use of out-of-date antibiotics, and consequently an often inappropriate consumption. In parallel the
intensive use of antibiotics in the hospitals of the western
countries, but also in the context of practices without any
therapeutic aims (i.e., prophylactic purposes and stimulation
of animal growth), associated with an increase of immunocompromised individuals participates in the emergence and
spread of antibiotic resistance.
15.3.6.1 Emergence and Spread of Antibiotic
Resistance Among Bacterial Pathogens
Adaptation and Spread Mechanisms
Antibiotics are categorized as bacteriostatic (i.e., growth
inhibition) or bactericidal (i.e., cell death) and show a
narrow or wide range of activity toward bacterial species.
Basic mechanisms of antibiotic action against bacterial cells
are inhibition of cell wall synthesis (penicillin, cephalosporin, or vancomycin), of protein synthesis (chloramphenicol, streptomycin, tetracycline), of nucleic acid synthesis
(quinolones), or of metabolic processes (sulfonamides).
Bacterial species differ in terms of their sensitivity toward
antibiotics, some exhibiting a high level of intrinsic resistance. Enhanced resistance toward an antibiotic or resistance
toward new antibiotic can also be acquired through
gene mutation or gain of new genes. Resistance mechanisms
and genetic determinants have been widely investigated,
and many of them have been identified (Levy and Marshall
2004). There are several molecular mechanisms that
include modifying or protecting the target, reducing the
membrane permeability, inactivating the antibiotic through
enzyme activity, or actively exporting an antibiotic from the
bacterial cell (efflux pump). These mechanisms are more or
less specific of an antibiotic and can act simultaneously.
Dissemination of resistance is mediated by clonal spread of
a particular resistant strain and/or by spreading of resistance
genes through horizontal gene transfer. The former is the
main explanation for the first resistance described within
bacterial pathogenic species. The latter was further involved
in the spread of resistance between taxonomically distantly
related species (Martinez et al. 2009). The location of
resistance genes on plasmids or transposons contributes to
intercellular transfer. These genes are also often associated
to integrons*, which capture genes by site-specific recombination, allowing intracellular mobility then favoring
multiresistance acquisition.
15 Environmental and Human Pathogenic Microorganisms
635