known as lipid II. One of the two D-alanine may be replaced
by a D-lactate (D-Lac), or D-serine (D-Ser) structures
and D-Ala-D-Lac-Ala-D or D-Ser, and thus become resistant
to vancomycin (Healy et al. 2000). The lipid II, which is the
precursor of peptidoglycan, also interacts with antibiotics,
proteins that form pores in the membrane (Breukink and de
Kruijff 2006). Multicellular organisms such as insects,
amphibians, mammals, and plants produce oligopeptides
that have antimicrobial activity (Zasloff 2002). The peptide
antibiotics destroy or weaken the microbial membrane,
leading to a loss of metabolites induced by pore formation,
resulting in cell death.
Ribosomes are the target of macrolide antibiotics types,
oxazolidinones (target 50S ribosomal subunit), tetracyclines,
and aminoglycosides (target 30S subunit). The activity
of protein biosynthesis is inactivated because the active
site of transpeptidation and more precisely the molecule
rRNA of the large subunit of ribosomes is inactivated in
the presence of antibiotic molecules.
Replication enzymes and DNA repair are targets of
fluoroquinolones, synthetic antibiotics that inhibit the activity of topoisomerases or gyrases (Drlica and Malik 2003).
The double-stranded DNA once broken cannot be repaired
by inactivated topoisomerase. The accumulation of breaks
in the DNA causes cell death.
Several antibiotics of natural origin, produced by
actinobacteria, interact with DNA. Antibiotics such as
enediyne produce direct covalent bonds with the DNA molecule (Liu et al. 2002), which prevents DNA replication, the
termination of transcription, and cell death.
It has been shown that antibiotics such as quinolones
(norfloxacin), the β-lactams (ampicillin), and aminoglycosides
(kanamycin) are bactericidal agents that cause the formation
of free radicals (hydroxyl) via the Fenton reaction, leading
eventually to cell death. In the same experiment, it was shown
that bacteriostatic drugs do not stimulate the production of free
radicals (Kohanski et al. 2007). The sulfonamides are
derivatives of para-aminobenzoic acid, which block the biosynthesis of tetrahydrofolate, and while trimethoprim is an
analog of a part of folic acid dihydropterin, thereby inhibiting
the enzyme dihydrofolate reductase, these two molecules are
therefore involved in the synthesis of dTMP nucleosides and
UTP, causing a depletion of the cell.
9.5.2 Types of Antibiotic Resistance
Development in an organism of a specific resistance to an
antibiotic can be achieved by accumulation of spontaneous
mutations or be induced by the stress response (SOS),
followed by positive selection. If the SOS system is
inactivated, the evolution of antibiotic resistance is slowed
(Cirz et al. 2005).
The presence of resistance genes in the genomes of
microorganisms has been described repeatedly. Antibiotic
resistance through methylation of the active site of the ribosome, the export of antibiotics from the cells by efflux
pumps or modification of antibiotics is well described.
These involve acetylation, phosphorylation, or adenylylation
of antibiotic molecules by specific enzymes such as the
kanamycin modifying enzymes.
Each microorganism producing a given antibiotic either
has no target for that antibiotic or also has resistance genes to
that same antibiotic, in order not to commit suicide. The set
of determinants of the genome that may provide resistance
against antibiotics is defined as the resistome (D’Costa et al.
2006) These resistance genes encode specific or nonspecific
transporters, modifying enzymes or enzyme that cause
degradation of the antibiotic or modification of the target
molecule. These genes are located in the chromosome and
often mobile elements such as plasmids, transposons, or
insertion sequences (IS) which enable their mobilization
to other microorganisms. It has been shown that bacteria
resistant to natural and synthetic antibiotics are able to
use antibiotics as sole carbon source (Dantas et al. 2008).
The horizontal transfer of resistance genes and degradation
of antibiotics to the pathogens of plants and animals represent a potential danger to the health of living organisms.
The discovery of new antibiotics from natural or synthetic is
therefore necessary to prevent the spread of pathogenic
microorganisms.
9.6
Physiological Responses
to Abiotic Stress*
9.6.1 Temperature Stress
Temperature is one of the most important factors that
influence the growth and survival of microorganisms.
When the temperature increases, the speed of chemical and
enzymatic reactions increases until a maximum temperature
beyond which cellular components (enzymes, nucleic acids,
proteins, etc.) are sensitive and denatured (Fig. 9.21a). This
leads in turn to inactivation of cellular functions, a growth
arrest, or cell death. Before cell death, there may be repair
and growth recovery if the temperature drops again.
At low temperatures, enzyme activities and bacterial
growth can continue more slowly. When the temperature
decreases, cell functions continue so long as the cytoplasmic membrane remains fluid. When the temperature is too
low, there is a tendency to gel, thus solidifying which
causes blockage of growth by stopping cell transport,
respiration, and energy production. However, at low
temperatures the prokaryotic cells in general are not
destroyed, only resting as dormant cells. This allows them
324
P. Normand et al.
by a D-lactate (D-Lac), or D-serine (D-Ser) structures
and D-Ala-D-Lac-Ala-D or D-Ser, and thus become resistant
to vancomycin (Healy et al. 2000). The lipid II, which is the
precursor of peptidoglycan, also interacts with antibiotics,
proteins that form pores in the membrane (Breukink and de
Kruijff 2006). Multicellular organisms such as insects,
amphibians, mammals, and plants produce oligopeptides
that have antimicrobial activity (Zasloff 2002). The peptide
antibiotics destroy or weaken the microbial membrane,
leading to a loss of metabolites induced by pore formation,
resulting in cell death.
Ribosomes are the target of macrolide antibiotics types,
oxazolidinones (target 50S ribosomal subunit), tetracyclines,
and aminoglycosides (target 30S subunit). The activity
of protein biosynthesis is inactivated because the active
site of transpeptidation and more precisely the molecule
rRNA of the large subunit of ribosomes is inactivated in
the presence of antibiotic molecules.
Replication enzymes and DNA repair are targets of
fluoroquinolones, synthetic antibiotics that inhibit the activity of topoisomerases or gyrases (Drlica and Malik 2003).
The double-stranded DNA once broken cannot be repaired
by inactivated topoisomerase. The accumulation of breaks
in the DNA causes cell death.
Several antibiotics of natural origin, produced by
actinobacteria, interact with DNA. Antibiotics such as
enediyne produce direct covalent bonds with the DNA molecule (Liu et al. 2002), which prevents DNA replication, the
termination of transcription, and cell death.
It has been shown that antibiotics such as quinolones
(norfloxacin), the β-lactams (ampicillin), and aminoglycosides
(kanamycin) are bactericidal agents that cause the formation
of free radicals (hydroxyl) via the Fenton reaction, leading
eventually to cell death. In the same experiment, it was shown
that bacteriostatic drugs do not stimulate the production of free
radicals (Kohanski et al. 2007). The sulfonamides are
derivatives of para-aminobenzoic acid, which block the biosynthesis of tetrahydrofolate, and while trimethoprim is an
analog of a part of folic acid dihydropterin, thereby inhibiting
the enzyme dihydrofolate reductase, these two molecules are
therefore involved in the synthesis of dTMP nucleosides and
UTP, causing a depletion of the cell.
9.5.2 Types of Antibiotic Resistance
Development in an organism of a specific resistance to an
antibiotic can be achieved by accumulation of spontaneous
mutations or be induced by the stress response (SOS),
followed by positive selection. If the SOS system is
inactivated, the evolution of antibiotic resistance is slowed
(Cirz et al. 2005).
The presence of resistance genes in the genomes of
microorganisms has been described repeatedly. Antibiotic
resistance through methylation of the active site of the ribosome, the export of antibiotics from the cells by efflux
pumps or modification of antibiotics is well described.
These involve acetylation, phosphorylation, or adenylylation
of antibiotic molecules by specific enzymes such as the
kanamycin modifying enzymes.
Each microorganism producing a given antibiotic either
has no target for that antibiotic or also has resistance genes to
that same antibiotic, in order not to commit suicide. The set
of determinants of the genome that may provide resistance
against antibiotics is defined as the resistome (D’Costa et al.
2006) These resistance genes encode specific or nonspecific
transporters, modifying enzymes or enzyme that cause
degradation of the antibiotic or modification of the target
molecule. These genes are located in the chromosome and
often mobile elements such as plasmids, transposons, or
insertion sequences (IS) which enable their mobilization
to other microorganisms. It has been shown that bacteria
resistant to natural and synthetic antibiotics are able to
use antibiotics as sole carbon source (Dantas et al. 2008).
The horizontal transfer of resistance genes and degradation
of antibiotics to the pathogens of plants and animals represent a potential danger to the health of living organisms.
The discovery of new antibiotics from natural or synthetic is
therefore necessary to prevent the spread of pathogenic
microorganisms.
9.6
Physiological Responses
to Abiotic Stress*
9.6.1 Temperature Stress
Temperature is one of the most important factors that
influence the growth and survival of microorganisms.
When the temperature increases, the speed of chemical and
enzymatic reactions increases until a maximum temperature
beyond which cellular components (enzymes, nucleic acids,
proteins, etc.) are sensitive and denatured (Fig. 9.21a). This
leads in turn to inactivation of cellular functions, a growth
arrest, or cell death. Before cell death, there may be repair
and growth recovery if the temperature drops again.
At low temperatures, enzyme activities and bacterial
growth can continue more slowly. When the temperature
decreases, cell functions continue so long as the cytoplasmic membrane remains fluid. When the temperature is too
low, there is a tendency to gel, thus solidifying which
causes blockage of growth by stopping cell transport,
respiration, and energy production. However, at low
temperatures the prokaryotic cells in general are not
destroyed, only resting as dormant cells. This allows them
324
P. Normand et al.