The
widespread use of antibiotics has led to a rapid expansion of antibiotic
resistance, particularly in Gram-positive bacteria, leading to an urgent need
to identify new anti-bacterial compound classes. The development of novel
antibiotics is generally hampered by slow, difficult to monitor and labor
intensive animal models for testing efficacy. These models usually correlate animal
survival and/or the number of retrieved bacteria from the tissues (an invasive
procedure) with compound activity. In recent years, advances in non-invasive in vivo imaging techniques have allowed
the detection of genetically modified bioluminescent bacteria and the real-time
visualization of the progression and/or resolution of infection in different organs.
The aim of this study was to compare the efficacy of Gram-positive antibiotics
against Staphylococcus aureus in i) a thigh infection model using an
invasive readout of colony forming units (cfu) retrieved from the infected
tissues, or ii) in an acute peritonitis
model using bioluminescent S. aureus (Xen-29
strain), which allows for the immediate visualization of the bacteria and sites
of infection. Both models were treated with approved antibiotics, as well as
novel internally developed antibiotics. Similar trends in antibiotic
effectiveness were observed in both models. In the acute peritonitis model there
was a correlation between recovered bioluminescent cfu and the observed bioluminescence
prior to organ harvest. Together, these results validate the use of
bioluminescent bacteria in non-invasive infection models, as they allow for real-time
in vivo monitoring and the rapid
efficacy testing and ranking of novel antimicrobial agents.