50 4 ART for Antibacterial Infection
In theory, the decline of NO levels may be resulted either from bNOS or from
iNOS because ART inhibits all kinds of NOS without discrimination. While
bNOS-derived low-level NO can protect bacteria, iNOS-derived high-level NO
must kill bacteria. Although ART can help antibiotics to kill bacteria through
blocking the protective NO from bNOS, it can also decrease the bactericidal NO
from iNOS. Fortunately, ART can also elevate the H 2 O 2 level by inhibiting CAT,
which directly causes bacterial death. Therefore, a net outcome of ART-antibiotic
combination is beneficial to enhance antibiotics’ antibacterial capacity.
In summary, ART synchronously inhibits bNOS and CAT, which can cause
the decrease of protective NO and simultaneous increase of bactericidal H 2 O 2 in
G+ bacteria. In G− bacteria without bNOS, ART still inhibits CAT and increases
H 2 O 2 , which also enhance antibiotic toxicity because ONOO− accumulation from
the reaction of NO with O 2 − would be augmented.
4.3.4 Conclusions
By choosing B. licheniformis and E. coli as representative G+ and G− bacteria,
and through stool culture and colony counting or serum NO determination, we
evaluated the in vivo sensitization of antibiotics by ART in mice with gastrointes-
tinal infections via daily live bacterial feeding. While bacteria protect themselves
from antibiotics through releasing NO, ART enhances the sensitivity of bacteria
to antibiotics upon inhibiting bNOS and CAT. Consequently, ART can accelerate
the antibacterial efficiency of CEF and RIF against bacteria. Importantly, ART
can assist AMP to repress the propagation of drug tolerant bacteria, which should
release an exciting news for helping combat superbug’s antibiotic resistance.
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