Related Experiment Videos
Virulence of non-beta-lactamase-mediated ampicillin-resistant Haemophilus influenzae
L G Rubin1, P M Mendelman, R M Rakita
1Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
Abstract:
We questioned whether strains of ampicillin-resistant, non-beta-lactamase-producing (AmpR NBLP) Haemophilus influenzae with lower affinity penicillin-binding proteins (PBPs) might have altered virulence. The virulence of resistant transformant strains and the susceptible recipient was compared using infant rats. Following intraperitoneal inoculation, there was a significantly lower mortality rate and incidence and magnitude of bacteremia with two of three transformants compared to the recipient strain. Reduced virulence was not associated with greater bactericidal activity of serum or human neutrophils or faster clearance of the transformant following intravenous injection. Heated rat or human plasma supported exponential growth of the recipient, but not the transformant, suggesting deficient in vivo multiplication. We conclude that H. influenzae with altered PBPs are less virulent in an infant rat model which may be related to differences in in vivo growth.
Insights
Ampicillin-resistant Haemophilus influenzae with altered penicillin-binding proteins (PBPs) showed reduced virulence in infant rats. This suggests that changes in PBPs may impact bacterial growth and infection severity.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Ampicillin resistance in Haemophilus influenzae is a growing concern.
- Non-beta-lactamase-producing (AmpR NBLP) strains with altered penicillin-binding proteins (PBPs) are emerging.
- The impact of altered PBPs on bacterial virulence is not well understood.
Purpose of the Study:
- To investigate the virulence of ampicillin-resistant, non-beta-lactamase-producing Haemophilus influenzae strains with altered penicillin-binding proteins (PBPs).
- To compare the virulence of these resistant strains against the susceptible recipient strain in a relevant animal model.
Main Methods:
- Comparison of virulence using an infant rat model following intraperitoneal inoculation.
- Assessment of mortality rates, bacteremia incidence and magnitude.
- Evaluation of serum and neutrophil bactericidal activity and intravenous clearance rates.
- In vitro growth studies in heated rat and human plasma.
Main Results:
- Two of three ampicillin-resistant transformant strains exhibited significantly lower mortality and bacteremia compared to the susceptible recipient strain.
- Reduced virulence was not linked to increased serum or neutrophil bactericidal activity or faster clearance.
- Resistant transformants showed deficient in vivo multiplication, as evidenced by impaired growth in heated plasma.
Conclusions:
- Haemophilus influenzae strains with altered PBPs demonstrate reduced virulence in the infant rat model.
- The decreased virulence may be attributed to impaired in vivo multiplication.
- These findings suggest a potential link between PBP alterations and reduced pathogenicity of H. influenzae.