Abstract
Silver carbene complexes (SCCs), a group of novel silver-based compounds capable of
gradually releasing silver ions, have shown significant antimicrobial activity against a wide
range of bacterial pathogens mainly isolated from human cases. The antimicrobial activity
against animal isolated pathogens has yet been done. The in vitro efficacy of two SCCs with
different carrier molecules (SCC1 with a methylated caffeine backbone and SCC22 with a
dichloroimidazolium backbone) was investigated against three important animal and
human pathogen species. SCC1 and SCC22 exhibited bacteriostatic and bactericidal effects
against multidrug resistant Salmonella Typhimurium (poultry isolate), E. coli 843 and E. coli
1568 (swine isolates), and the poultry field isolates Salmonella Heidelberg, Salmonella
Enteritidis, and Salmonella Montevideo with MICs and MBCs ranged from 16-21 µM (6-8
µg/mL) and 16-32 µM (6-12 µg/mL), respectively. Clostridium perfringens type A was
sensitive to both SCC1 and SCC22 with the MICs being 11 (4 µg/mL) and 21 µM (8 µg/mL),
respectively. These values were comparable to the MICs and MBCs for silver acetate. The
MBCs against C. perfringens was >85 µM for SCCs and >192 µM for silver acetate (>32 µg/mL
for all compounds). Ten hours incubation of C. perfringens with 40 µg/mL of all three
products showed down regulation of virulence genes plc and netB, suggesting viable cells
and silver can modulate the virulence. Treating the C. perfringens with higher concentration
(100 µg/mL) of each SCC for 10 hours inhibited more bacteria compared to the untreated
bacterial cells, however, no differences in the ultrastructure of lysed bacteria were seen and
this concentration might not induce viable but non-culturable (VBNC) state as suggested by
transmission electron microscopy findings. SCCs showed a broad antimicrobial activity
against all bacterial species tested including multidrug resistant pathogens. Both SCCs
demonstrated inhibitory effect against the Gram-positive anaerobic C. perfringens type A
which could have a high accumulation capacity for silver ion. These data suggest that SCCs
may represent a novel class of broad-spectrum antimicrobial agents, which may be used to
reduce the burden of pathogenic bacteria in the gastrointestinal tract of poultry.
gradually releasing silver ions, have shown significant antimicrobial activity against a wide
range of bacterial pathogens mainly isolated from human cases. The antimicrobial activity
against animal isolated pathogens has yet been done. The in vitro efficacy of two SCCs with
different carrier molecules (SCC1 with a methylated caffeine backbone and SCC22 with a
dichloroimidazolium backbone) was investigated against three important animal and
human pathogen species. SCC1 and SCC22 exhibited bacteriostatic and bactericidal effects
against multidrug resistant Salmonella Typhimurium (poultry isolate), E. coli 843 and E. coli
1568 (swine isolates), and the poultry field isolates Salmonella Heidelberg, Salmonella
Enteritidis, and Salmonella Montevideo with MICs and MBCs ranged from 16-21 µM (6-8
µg/mL) and 16-32 µM (6-12 µg/mL), respectively. Clostridium perfringens type A was
sensitive to both SCC1 and SCC22 with the MICs being 11 (4 µg/mL) and 21 µM (8 µg/mL),
respectively. These values were comparable to the MICs and MBCs for silver acetate. The
MBCs against C. perfringens was >85 µM for SCCs and >192 µM for silver acetate (>32 µg/mL
for all compounds). Ten hours incubation of C. perfringens with 40 µg/mL of all three
products showed down regulation of virulence genes plc and netB, suggesting viable cells
and silver can modulate the virulence. Treating the C. perfringens with higher concentration
(100 µg/mL) of each SCC for 10 hours inhibited more bacteria compared to the untreated
bacterial cells, however, no differences in the ultrastructure of lysed bacteria were seen and
this concentration might not induce viable but non-culturable (VBNC) state as suggested by
transmission electron microscopy findings. SCCs showed a broad antimicrobial activity
against all bacterial species tested including multidrug resistant pathogens. Both SCCs
demonstrated inhibitory effect against the Gram-positive anaerobic C. perfringens type A
which could have a high accumulation capacity for silver ion. These data suggest that SCCs
may represent a novel class of broad-spectrum antimicrobial agents, which may be used to
reduce the burden of pathogenic bacteria in the gastrointestinal tract of poultry.